text stringlengths 26 3.6k | page_title stringlengths 1 71 | source stringclasses 1
value | token_count int64 10 512 | id stringlengths 2 8 | url stringlengths 31 117 | topic stringclasses 4
values | section stringlengths 4 49 ⌀ | sublist stringclasses 9
values |
|---|---|---|---|---|---|---|---|---|
Al-Nasawi wrote in the early 11th century that mathematicians had not agreed on the form of the numerals, but most of them had agreed to train themselves with the forms now known as Eastern Arabic numerals. The oldest specimens of the written numerals available are from Egypt and date to 873–874 AD. They show three forms of the numeral "2" and two forms of the numeral "3", and these variations indicate the divergence between what later became known as the Eastern Arabic numerals and the Western Arabic numerals. The Western Arabic numerals came to be used in the Maghreb and Al-Andalus from the 10th century onward. Some amount of consistency in the Western Arabic numeral forms endured from the 10th century, found in a Latin manuscript of Isidore of Seville's from 976 and the Gerbertian abacus, into the 12th and 13th centuries, in early manuscripts of translations from the city of Toledo.
Calculations were originally performed using a dust board (, Latin: ), which involved writing symbols with a stylus and erasing them. The use of the dust board appears to have introduced a divergence in terminology as well: whereas the Hindu reckoning was called in the east, it was called 'calculation with dust' in the west. The numerals themselves were referred to in the west as 'dust figures' or 'dust letters'. Al-Uqlidisi later invented a system of calculations with ink and paper 'without board and erasing' ().
A popular myth claims that the symbols were designed to indicate their numeric value through the number of angles they contained, but there is no contemporary evidence of this, and the myth is difficult to reconcile with any digits past 4.
Adoption and spread
The first mentions of the numerals from 1 to 9 in the West are found in the 976 , an illuminated collection of various historical documents covering a period from antiquity to the 10th century in Hispania. Other texts show that numbers from 1 to 9 were occasionally supplemented by a placeholder known as , represented as a circle or wheel, reminiscent of the eventual symbol for zero. The Arabic term for zero is (), transliterated into Latin as , which became the English word cipher. | Arabic numerals | Wikipedia | 466 | 1786 | https://en.wikipedia.org/wiki/Arabic%20numerals | Mathematics | Language | null |
From the 980s, Gerbert of Aurillac (later Pope Sylvester II) used his position to spread knowledge of the numerals in Europe. Gerbert studied in Barcelona in his youth. He was known to have requested mathematical treatises concerning the astrolabe from Lupitus of Barcelona after he had returned to France.
The reception of Arabic numerals in the West was gradual and lukewarm, as other numeral systems circulated in addition to the older Roman numbers. As a discipline, the first to adopt Arabic numerals as part of their own writings were astronomers and astrologists, evidenced from manuscripts surviving from mid-12th-century Bavaria. Reinher of Paderborn (1140–1190) used the numerals in his calendrical tables to calculate the dates of Easter more easily in his text .
Italy
Leonardo Fibonacci was a Pisan mathematician who had studied in the Pisan trading colony of Bugia, in what is now Algeria, and he endeavored to promote the numeral system in Europe with his 1202 book :
When my father, who had been appointed by his country as public notary in the customs at Bugia acting for the Pisan merchants going there, was in charge, he summoned me to him while I was still a child, and having an eye to usefulness and future convenience, desired me to stay there and receive instruction in the school of accounting. There, when I had been introduced to the art of the Indians' nine symbols through remarkable teaching, knowledge of the art very soon pleased me above all else and I came to understand it.
The s analysis highlighting the advantages of positional notation was widely influential. Likewise, Fibonacci's use of the Béjaïa digits in his exposition ultimately led to their widespread adoption in Europe. Fibonacci's work coincided with the European commercial revolution of the 12th and 13th centuries centered in Italy. Positional notation facilitated complex calculations (such as currency conversion) to be completed more quickly than was possible with the Roman system. In addition, the system could handle larger numbers, did not require a separate reckoning tool, and allowed the user to check their work without repeating the entire procedure. Late medieval Italian merchants did not stop using Roman numerals or other reckoning tools: instead, Arabic numerals were adopted for use in addition to their preexisting methods.
Europe | Arabic numerals | Wikipedia | 491 | 1786 | https://en.wikipedia.org/wiki/Arabic%20numerals | Mathematics | Language | null |
By the late 14th century, only a few texts using Arabic numerals appeared outside of Italy. This suggests that the use of Arabic numerals in commercial practice, and the significant advantage they conferred, remained a virtual Italian monopoly until the late 15th century. This may in part have been due to language barriers: although Fibonacci's was written in Latin, the Italian abacus traditions were predominantly written in Italian vernaculars that circulated in the private collections of abacus schools or individuals.
The European acceptance of the numerals was accelerated by the invention of the printing press, and they became widely known during the 15th century. Their use grew steadily in other centers of finance and trade such as Lyon. Early evidence of their use in Britain includes: an equal hour horary quadrant from 1396, in England, a 1445 inscription on the tower of Heathfield Church, Sussex; a 1448 inscription on a wooden lych-gate of Bray Church, Berkshire; and a 1487 inscription on the belfry door at Piddletrenthide church, Dorset; and in Scotland a 1470 inscription on the tomb of the first Earl of Huntly in Elgin Cathedral. In central Europe, the King of Hungary Ladislaus the Posthumous, started the use of Arabic numerals, which appear for the first time in a royal document of 1456.
By the mid-16th century, they had been widely adopted in Europe, and by 1800 had almost completely replaced the use of counting boards and Roman numerals in accounting. Roman numerals were mostly relegated to niche uses such as years and numbers on clock faces. | Arabic numerals | Wikipedia | 329 | 1786 | https://en.wikipedia.org/wiki/Arabic%20numerals | Mathematics | Language | null |
Russia
Prior to the introduction of Arabic numerals, Cyrillic numerals, derived from the Cyrillic alphabet, were used by South and East Slavs. The system was used in Russia as late as the early 18th century, although it was formally replaced in official use by Peter the Great in 1699. Reasons for Peter's switch from the alphanumerical system are believed to go beyond a surface-level desire to imitate the West. Historian Peter Brown makes arguments for sociological, militaristic, and pedagogical reasons for the change. At a broad, societal level, Russian merchants, soldiers, and officials increasingly came into contact with counterparts from the West and became familiar with the communal use of Arabic numerals. Peter also covertly travelled throughout Northern Europe from 1697 to 1698 during his Grand Embassy and was likely informally exposed to Western mathematics during this time. The Cyrillic system was found to be inferior for calculating practical kinematic values, such as the trajectories and parabolic flight patterns of artillery. With its use, it was difficult to keep pace with Arabic numerals in the growing field of ballistics, whereas Western mathematicians such as John Napier had been publishing on the topic since 1614.
China
The Chinese Shang dynasty numerals from the 14th century BC predates the Indian Brahmi numerals by over 1000 years and shows substantial similarity to the Brahmi numerals. Similar to the modern Arabic numerals, the Shang dynasty numeral system was also decimal based and positional.
While positional Chinese numeral systems such as the counting rod system and Suzhou numerals had been in use prior to the introduction of modern Arabic numerals, the externally-developed system was eventually introduced to medieval China by the Hui people. In the early 17th century, European-style Arabic numerals were introduced by Spanish and Portuguese Jesuits.
Encoding
The ten Arabic numerals are encoded in virtually every character set designed for electric, radio, and digital communication, such as Morse code. They are encoded in ASCII (and therefore in Unicode encodings) at positions 0x30 to 0x39. Masking all but the four least-significant binary digits gives the value of the decimal digit, a design decision facilitating the digitization of text onto early computers. EBCDIC used a different offset, but also possessed the aforementioned masking property. | Arabic numerals | Wikipedia | 483 | 1786 | https://en.wikipedia.org/wiki/Arabic%20numerals | Mathematics | Language | null |
The acre ( ) is a unit of land area used in the British imperial and the United States customary systems. It is traditionally defined as the area of one chain by one furlong (66 by 660 feet), which is exactly equal to 10 square chains, of a square mile, 4,840 square yards, or 43,560 square feet, and approximately 4,047 m2, or about 40% of a hectare. Based upon the international yard and pound agreement of 1959, an acre may be declared as exactly 4,046.8564224 square metres. The acre is sometimes abbreviated ac but is usually spelled out as the word "acre".
Traditionally, in the Middle Ages, an acre was conceived of as the area of land that could be ploughed by one man using a team of eight oxen in one day.
The acre is still a statutory measure in the United States. Both the international acre and the US survey acre are in use, but they differ by only four parts per million (see below). The most common use of the acre is to measure tracts of land.
The acre is used in many established and former Commonwealth of Nations countries by custom. In a few, it continues as a statute measure, although not since 2010 in the UK, and not for decades in Australia, New Zealand, and South Africa. In many places where it is not a statute measure, it is still lawful to "use for trade" if given as supplementary information and is not used for land registration.
Description
One acre equals (0.0015625) square mile, 4,840 square yards, 43,560 square feet, or about (see below). While all modern variants of the acre contain 4,840 square yards, there are alternative definitions of a yard, so the exact size of an acre depends upon the particular yard on which it is based. Originally, an acre was understood as a strip of land sized at forty perches (660 ft, or 1 furlong) long and four perches (66 ft) wide; this may have also been understood as an approximation of the amount of land a yoke of oxen could plough in one day (a furlong being "a furrow long"). A square enclosing one acre is approximately 69.57 yards, or 208 feet 9 inches (), on a side. As a unit of measure, an acre has no prescribed shape; any area of 43,560 square feet is an acre. | Acre | Wikipedia | 506 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
US survey acres
In the international yard and pound agreement of 1959, the United States and five countries of the Commonwealth of Nations defined the international yard to be exactly 0.9144 metre. The US authorities decided that, while the refined definition would apply nationally in all other respects, the US survey foot (and thus the survey acre) would continue 'until such a time as it becomes desirable and expedient to readjust [it]'. By inference, an "international acre" may be calculated as exactly square metres but it does not have a basis in any international agreement.
Both the international acre and the US survey acre contain of a square mile or 4,840 square yards, but alternative definitions of a yard are used (see survey foot and survey yard), so the exact size of an acre depends upon the yard upon which it is based. The US survey acre is about 4,046.872 square metres; its exact value ( m2) is based on an inch defined by 1 metre = 39.37 inches exactly, as established by the Mendenhall Order of 1893. Surveyors in the United States use both international and survey feet, and consequently, both varieties of acre.
Since the difference between the US survey acre and international acre (0.016 square metres, 160 square centimetres or 24.8 square inches), is only about a quarter of the size of an A4 sheet or US letter, it is usually not important which one is being discussed. Areas are seldom measured with sufficient accuracy for the different definitions to be detectable.
In October 2019, the US National Geodetic Survey and the National Institute of Standards and Technology announced their joint intent to end the "temporary" continuance of the US survey foot, mile, and acre units (as permitted by their 1959 decision, above), with effect from the end of 2022.
Spanish acre
The Puerto Rican cuerda () is sometimes called the "Spanish acre" in the continental United States. | Acre | Wikipedia | 401 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
Use
The acre is commonly used in many current and former Commonwealth countries by custom, and in a few it continues as a statute measure. These include Antigua and Barbuda, American Samoa, The Bahamas, Belize, the British Virgin Islands, Canada, the Cayman Islands, Dominica, the Falkland Islands, Grenada, Ghana, Guam, the Northern Mariana Islands, Jamaica, Montserrat, Samoa, Saint Lucia, St. Helena, St. Kitts and Nevis, St. Vincent and the Grenadines, Turks and Caicos, the United Kingdom, the United States and the US Virgin Islands.
Republic of Ireland
In the Republic of Ireland, the hectare is legally used under European units of measurement directives; however, the acre (the same standard statute as used in the UK, not the old Irish acre, which was of a different size) is still widely used, especially in agriculture.
Indian subcontinent
In India, residential plots are measured in square feet or square metre, while agricultural land is measured in acres. In Sri Lanka, the division of an acre into 160 perches or 4 roods is common.
In Pakistan, residential plots are measured in (20 = 1 = 605 sq yards) and open/agriculture land measurement is in acres (8 = 1 acre) and (25 acres = 1 = 200 ), and .
United Kingdom
Its use as a primary unit for trade in the United Kingdom ceased to be permitted from 1 October 1995, due to the 1994 amendment of the Weights and Measures Act, where it was replaced by the hectare though its use as a supplementary unit continues to be permitted indefinitely. This was with the exemption of Land registration, which records the sale and possession of land, in 2010 HM Land Registry ended its exemption. The measure is still used to communicate with the public and informally (non-contract) by the farming and property industries.
Equivalence to other units of area
1 international acre is equal to the following metric units:
0.40468564224 hectare (A square with 100 m sides has an area of 1 hectare.)
4,046.8564224 square metres (or a square with approximately 63.61 m sides)
1 United States survey acre is equal to:
0.404687261 hectare
4,046.87261 square metres (1 square kilometre is equal to 247.105 acres) | Acre | Wikipedia | 481 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
1 acre (both variants) is equal to the following customary units:
66 feet × 660 feet (43,560 square feet)
10 square chains (1 chain = 66 feet = 22 yards = 4 rods = 100 links)
1 acre is approximately 208.71 feet × 208.71 feet (a square)
4,840 square yards
43,560 square feet
160 perches. A perch is equal to a square rod (1 square rod is 0.00625 acre)
4 roods
A furlong by a chain (furlong 220 yards, chain 22 yards)
40 rods by 4 rods, 160 rods2 (historically fencing was often sold in 40 rod lengths)
(0.0015625) square mile (1 square mile is equal to 640 acres)
Perhaps the easiest way for US residents to envision an acre is as a rectangle measuring 88 yards by 55 yards ( of 880 yards by of 880 yards), about the size of a standard American football field. To be more exact, one acre is 90.75% of a 100-yd-long by 53.33-yd-wide American football field (without the end zone). The full field, including the end zones, covers about .
For residents of other countries, the acre might be envisioned as rather more than half of a football pitch.
Historical origin
The word acre is derived from the Norman, attested for the first time in a text of Fécamp in 1006 to the meaning of «agrarian measure». Acre dates back to the old Scandinavian akr “cultivated field, ploughed land” which is perpetuated in Icelandic and the Faroese “field (wheat)”, Norwegian and Swedish , Danish “field”, cognate with German , Dutch , Latin , Sanskrit , and Greek (). In English, an obsolete variant spelling was aker.
According to the Act on the Composition of Yards and Perches, dating from around 1300, an acre is "40 perches [rods] in length and four in breadth", meaning 220 yards by 22 yards. As detailed in the diagram, an acre was roughly the amount of land tillable by a yoke of oxen in one day. | Acre | Wikipedia | 444 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
Before the enactment of the metric system, many countries in Europe used their own official acres. In France, the traditional unit of area was the arpent carré, a measure based on the Roman system of land measurement.
The was used only in Normandy (and neighbouring places outside its traditional borders), but its value varied greatly across Normandy, ranging from 3,632 to 9,725 square metres, with 8,172 square metres being the most frequent value. But inside the same of Normandy, for instance in pays de Caux, the farmers (still in the 20th century) made the difference between the (68 ares, 66 centiares) and the (56 to 65 ca). The Normandy was usually divided in 4 (roods) and 160 square , like the English acre.
The Normandy was equal to 1.6 , the unit of area more commonly used in Northern France outside of Normandy. In Canada, the Paris used in Quebec before the metric system was adopted is sometimes called "French acre" in English, even though the Paris and the Normandy were two very different units of area in ancient France (the Paris became the unit of area of French Canada, whereas the Normandy was never used in French Canada).
In Germany, the Netherlands, and Eastern Europe the traditional unit of area was . Like the acre, the morgen was a unit of ploughland, representing a strip that could be ploughed by one man and an ox or horse in a morning. There were many variants of the morgen, differing between the different German territories, ranging from . It was also used in Old Prussia, in the Balkans, Norway, and Denmark, where it was equal to about .
Statutory values for the acre were enacted in England, and subsequently the United Kingdom, by acts of:
Edward I
Edward III
Henry VIII
George IV
Queen Victoria – the British Weights and Measures Act of 1878 defined it as containing 4,840 square yards.
Historically, the size of farms and landed estates in the United Kingdom was usually expressed in acres (or acres, roods, and perches), even if the number of acres was so large that it might conveniently have been expressed in square miles. For example, a certain landowner might have been said to own 32,000 acres of land, not 50 square miles of land. | Acre | Wikipedia | 470 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
The acre is related to the square mile, with 640 acres making up one square mile. One mile is 5280 feet (1760 yards). In western Canada and the western United States, divisions of land area were typically based on the square mile, and fractions thereof. If the square mile is divided into quarters, each quarter has a side length of mile (880 yards) and is square mile in area, or 160 acres. These subunits are typically then again divided into quarters, with each side being mile long, and being of a square mile in area, or 40 acres. In the United States, farmland was typically divided as such, and the phrase "the back 40" refers to the 40-acre parcel to the back of the farm. Most of the Canadian Prairie Provinces and the US Midwest are on square-mile grids for surveying purposes.
Legacy units
Customary acre – The customary acre was roughly similar to the Imperial acre, but it was subject to considerable local variation similar to the variation in carucates, virgates, bovates, nooks, and farundels. These may have been multiples of the customary acre, rather than the statute acre.
Builder's acre = an even or , used in US real-estate development to simplify the math and for marketing. It is nearly 10% smaller than a survey acre, and the discrepancy has led to lawsuits alleging misrepresentation.
Feddan - Middle Eastern measurement unit, .
Scottish acre = 1.3 Imperial acres (5,080 m2, an obsolete Scottish measurement)
Irish acre =
Cheshire acre =
Stremma or Greek acre ≈ 10,000 square Greek feet, but now set at exactly 1,000 square metres (a similar unit was the zeugarion)
Dunam or Turkish acre ≈ 1,600 square Turkish paces, but now set at exactly 1,000 square metres (a similar unit was the çift)
Actus quadratus or Roman acre ≈ 14,400 square Roman feet (about 1,260 square metres)
God's Acre – a synonym for a churchyard.
Long acre the grass strip on either side of a road that may be used for illicit grazing.
Town acre was a term used in early 19th century in the planning of towns on a grid plan, such as Adelaide, South Australia and Wellington, New Plymouth and Nelson in New Zealand. The land was divided into plots of an Imperial acre, and these became known as town acres. | Acre | Wikipedia | 502 | 1797 | https://en.wikipedia.org/wiki/Acre | Physical sciences | Area | null |
Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known forms of life, it is often referred to as the "molecular unit of currency" for intracellular energy transfer.
When consumed in a metabolic process, ATP converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. It is also a precursor to DNA and RNA, and is used as a coenzyme. An average adult human processes around 50 kilograms (about 100 moles) daily.
From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the triphosphate.
Structure
ATP consists of an adenine attached by the #9-nitrogen atom to the 1′ carbon atom of a sugar (ribose), which in turn is attached at the 5' carbon atom of the sugar to a triphosphate group. In its many reactions related to metabolism, the adenine and sugar groups remain unchanged, but the triphosphate is converted to di- and monophosphate, giving respectively the derivatives ADP and AMP. The three phosphoryl groups are labeled as alpha (α), beta (β), and, for the terminal phosphate, gamma (γ).
In neutral solution, ionized ATP exists mostly as ATP4−, with a small proportion of ATP3−.
Metal cation binding
Polyanionic and featuring a potentially chelating polyphosphate group, ATP binds metal cations with high affinity. The binding constant for is (). The binding of a divalent cation, almost always magnesium, strongly affects the interaction of ATP with various proteins. Due to the strength of the ATP-Mg2+ interaction, ATP exists in the cell mostly as a complex with bonded to the phosphate oxygen centers.
A second magnesium ion is critical for ATP binding in the kinase domain. The presence of Mg2+ regulates kinase activity. It is interesting from an RNA world perspective that ATP can carry a Mg ion which catalyzes RNA polymerization.
Chemical properties
Salts of ATP can be isolated as colorless solids. | Adenosine triphosphate | Wikipedia | 492 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
ATP is stable in aqueous solutions between pH 6.8 and 7.4 (in the absence of catalysts). At more extreme pH levels, it rapidly hydrolyses to ADP and phosphate. Living cells maintain the ratio of ATP to ADP at a point ten orders of magnitude from equilibrium, with ATP concentrations fivefold higher than the concentration of ADP. In the context of biochemical reactions, the P-O-P bonds are frequently referred to as high-energy bonds.
Reactive aspects
The hydrolysis of ATP into ADP and inorganic phosphate
ATP(aq) + (l) = ADP(aq) + HPO(aq) + H(aq)
releases of enthalpy. This may differ under physiological conditions if the reactant and products are not exactly in these ionization states. The values of the free energy released by cleaving either a phosphate (Pi) or a pyrophosphate (PPi) unit from ATP at standard state concentrations of 1 mol/L at pH 7 are:
ATP + → ADP + Pi ΔG°' = −30.5 kJ/mol (−7.3 kcal/mol)
ATP + → AMP + PPi ΔG°' = −45.6 kJ/mol (−10.9 kcal/mol)
These abbreviated equations at a pH near 7 can be written more explicitly (R = adenosyl):
[RO-P(O)2-O-P(O)2-O-PO3]4− + → [RO-P(O)2-O-PO3]3− + [HPO4]2− + H+
[RO-P(O)2-O-P(O)2-O-PO3]4− + → [RO-PO3]2− + [HO3P-O-PO3]3− + H+
At cytoplasmic conditions, where the ADP/ATP ratio is 10 orders of magnitude from equilibrium, the ΔG is around −57 kJ/mol. | Adenosine triphosphate | Wikipedia | 439 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
Along with pH, the free energy change of ATP hydrolysis is also associated with Mg2+ concentration, from ΔG°' = −35.7 kJ/mol at a Mg2+ concentration of zero, to ΔG°' = −31 kJ/mol at [Mg2+] = 5 mM. Higher concentrations of Mg2+ decrease free energy released in the reaction due to binding of Mg2+ ions to negatively charged oxygen atoms of ATP at pH 7.
Production from AMP and ADP
Production, aerobic conditions
A typical intracellular concentration of ATP may be 1–10 μmol per gram of tissue in a variety of eukaryotes. The dephosphorylation of ATP and rephosphorylation of ADP and AMP occur repeatedly in the course of aerobic metabolism.
ATP can be produced by a number of distinct cellular processes; the three main pathways in eukaryotes are (1) glycolysis, (2) the citric acid cycle/oxidative phosphorylation, and (3) beta-oxidation. The overall process of oxidizing glucose to carbon dioxide, the combination of pathways 1 and 2, known as cellular respiration, produces about 30 equivalents of ATP from each molecule of glucose.
ATP production by a non-photosynthetic aerobic eukaryote occurs mainly in the mitochondria, which comprise nearly 25% of the volume of a typical cell.
Glycolysis
In glycolysis, glucose and glycerol are metabolized to pyruvate. Glycolysis generates two equivalents of ATP through substrate phosphorylation catalyzed by two enzymes, phosphoglycerate kinase (PGK) and pyruvate kinase. Two equivalents of nicotinamide adenine dinucleotide (NADH) are also produced, which can be oxidized via the electron transport chain and result in the generation of additional ATP by ATP synthase. The pyruvate generated as an end-product of glycolysis is a substrate for the Krebs Cycle. | Adenosine triphosphate | Wikipedia | 442 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
Glycolysis is viewed as consisting of two phases with five steps each. In phase 1, "the preparatory phase", glucose is converted to 2 d-glyceraldehyde-3-phosphate (g3p). One ATP is invested in Step 1, and another ATP is invested in Step 3. Steps 1 and 3 of glycolysis are referred to as "Priming Steps". In Phase 2, two equivalents of g3p are converted to two pyruvates. In Step 7, two ATP are produced. Also, in Step 10, two further equivalents of ATP are produced. In Steps 7 and 10, ATP is generated from ADP. A net of two ATPs is formed in the glycolysis cycle. The glycolysis pathway is later associated with the Citric Acid Cycle which produces additional equivalents of ATP.
Regulation
In glycolysis, hexokinase is directly inhibited by its product, glucose-6-phosphate, and pyruvate kinase is inhibited by ATP itself. The main control point for the glycolytic pathway is phosphofructokinase (PFK), which is allosterically inhibited by high concentrations of ATP and activated by high concentrations of AMP. The inhibition of PFK by ATP is unusual since ATP is also a substrate in the reaction catalyzed by PFK; the active form of the enzyme is a tetramer that exists in two conformations, only one of which binds the second substrate fructose-6-phosphate (F6P). The protein has two binding sites for ATP – the active site is accessible in either protein conformation, but ATP binding to the inhibitor site stabilizes the conformation that binds F6P poorly. A number of other small molecules can compensate for the ATP-induced shift in equilibrium conformation and reactivate PFK, including cyclic AMP, ammonium ions, inorganic phosphate, and fructose-1,6- and -2,6-biphosphate.
Citric acid cycle | Adenosine triphosphate | Wikipedia | 430 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
In the mitochondrion, pyruvate is oxidized by the pyruvate dehydrogenase complex to the acetyl group, which is fully oxidized to carbon dioxide by the citric acid cycle (also known as the Krebs cycle). Every "turn" of the citric acid cycle produces two molecules of carbon dioxide, one equivalent of ATP guanosine triphosphate (GTP) through substrate-level phosphorylation catalyzed by succinyl-CoA synthetase, as succinyl-CoA is converted to succinate, three equivalents of NADH, and one equivalent of FADH2. NADH and FADH2 are recycled (to NAD+ and FAD, respectively) by oxidative phosphorylation, generating additional ATP. The oxidation of NADH results in the synthesis of 2–3 equivalents of ATP, and the oxidation of one FADH2 yields between 1–2 equivalents of ATP. The majority of cellular ATP is generated by this process. Although the citric acid cycle itself does not involve molecular oxygen, it is an obligately aerobic process because O2 is used to recycle the NADH and FADH2. In the absence of oxygen, the citric acid cycle ceases.
The generation of ATP by the mitochondrion from cytosolic NADH relies on the malate-aspartate shuttle (and to a lesser extent, the glycerol-phosphate shuttle) because the inner mitochondrial membrane is impermeable to NADH and NAD+. Instead of transferring the generated NADH, a malate dehydrogenase enzyme converts oxaloacetate to malate, which is translocated to the mitochondrial matrix. Another malate dehydrogenase-catalyzed reaction occurs in the opposite direction, producing oxaloacetate and NADH from the newly transported malate and the mitochondrion's interior store of NAD+. A transaminase converts the oxaloacetate to aspartate for transport back across the membrane and into the intermembrane space. | Adenosine triphosphate | Wikipedia | 445 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
In oxidative phosphorylation, the passage of electrons from NADH and FADH2 through the electron transport chain releases the energy to pump protons out of the mitochondrial matrix and into the intermembrane space. This pumping generates a proton motive force that is the net effect of a pH gradient and an electric potential gradient across the inner mitochondrial membrane. Flow of protons down this potential gradient – that is, from the intermembrane space to the matrix – yields ATP by ATP synthase. Three ATP are produced per turn.
Although oxygen consumption appears fundamental for the maintenance of the proton motive force, in the event of oxygen shortage (hypoxia), intracellular acidosis (mediated by enhanced glycolytic rates and ATP hydrolysis), contributes to mitochondrial membrane potential and directly drives ATP synthesis.
Most of the ATP synthesized in the mitochondria will be used for cellular processes in the cytosol; thus it must be exported from its site of synthesis in the mitochondrial matrix. ATP outward movement is favored by the membrane's electrochemical potential because the cytosol has a relatively positive charge compared to the relatively negative matrix. For every ATP transported out, it costs 1 H+. Producing one ATP costs about 3 H+. Therefore, making and exporting one ATP requires 4H+. The inner membrane contains an antiporter, the ADP/ATP translocase, which is an integral membrane protein used to exchange newly synthesized ATP in the matrix for ADP in the intermembrane space.
Regulation
The citric acid cycle is regulated mainly by the availability of key substrates, particularly the ratio of NAD+ to NADH and the concentrations of calcium, inorganic phosphate, ATP, ADP, and AMP. Citrate – the ion that gives its name to the cycle – is a feedback inhibitor of citrate synthase and also inhibits PFK, providing a direct link between the regulation of the citric acid cycle and glycolysis.
Beta oxidation | Adenosine triphosphate | Wikipedia | 408 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
In the presence of air and various cofactors and enzymes, fatty acids are converted to acetyl-CoA. The pathway is called beta-oxidation. Each cycle of beta-oxidation shortens the fatty acid chain by two carbon atoms and produces one equivalent each of acetyl-CoA, NADH, and FADH2. The acetyl-CoA is metabolized by the citric acid cycle to generate ATP, while the NADH and FADH2 are used by oxidative phosphorylation to generate ATP. Dozens of ATP equivalents are generated by the beta-oxidation of a single long acyl chain.
Regulation
In oxidative phosphorylation, the key control point is the reaction catalyzed by cytochrome c oxidase, which is regulated by the availability of its substrate – the reduced form of cytochrome c. The amount of reduced cytochrome c available is directly related to the amounts of other substrates:
which directly implies this equation:
Thus, a high ratio of [NADH] to [NAD+] or a high ratio of [ADP] [Pi] to [ATP] imply a high amount of reduced cytochrome c and a high level of cytochrome c oxidase activity. An additional level of regulation is introduced by the transport rates of ATP and NADH between the mitochondrial matrix and the cytoplasm.
Ketosis
Ketone bodies can be used as fuels, yielding 22 ATP and 2 GTP molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce reducing equivalents (NADH and FADH2), via the citric acid cycle. Ketone bodies cannot be used as fuel by the liver, because the liver lacks the enzyme β-ketoacyl-CoA transferase, also called thiolase. Acetoacetate in low concentrations is taken up by the liver and undergoes detoxification through the methylglyoxal pathway which ends with lactate. Acetoacetate in high concentrations is absorbed by cells other than those in the liver and enters a different pathway via 1,2-propanediol. Though the pathway follows a different series of steps requiring ATP, 1,2-propanediol can be turned into pyruvate. | Adenosine triphosphate | Wikipedia | 507 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
Production, anaerobic conditions
Fermentation is the metabolism of organic compounds in the absence of air. It involves substrate-level phosphorylation in the absence of a respiratory electron transport chain. The equation for the reaction of glucose to form lactic acid is:
+ 2 ADP + 2 Pi → 2 + 2 ATP + 2
Anaerobic respiration is respiration in the absence of . Prokaryotes can utilize a variety of electron acceptors. These include nitrate, sulfate, and carbon dioxide.
ATP replenishment by nucleoside diphosphate kinases
ATP can also be synthesized through several so-called "replenishment" reactions catalyzed by the enzyme families of nucleoside diphosphate kinases (NDKs), which use other nucleoside triphosphates as a high-energy phosphate donor, and the ATP:guanido-phosphotransferase family.
ATP production during photosynthesis
In plants, ATP is synthesized in the thylakoid membrane of the chloroplast. The process is called photophosphorylation. The "machinery" is similar to that in mitochondria except that light energy is used to pump protons across a membrane to produce a proton-motive force. ATP synthase then ensues exactly as in oxidative phosphorylation. Some of the ATP produced in the chloroplasts is consumed in the Calvin cycle, which produces triose sugars.
ATP recycling
The total quantity of ATP in the human body is about 0.1 mol/L. The majority of ATP is recycled from ADP by the aforementioned processes. Thus, at any given time, the total amount of ATP + ADP remains fairly constant.
The energy used by human cells in an adult requires the hydrolysis of 100 to 150 mol/L of ATP daily, which means a human will typically use their body weight worth of ATP over the course of the day. Each equivalent of ATP is recycled 1000–1500 times during a single day (), at approximately 9×1020 molecules/s.
Biochemical functions
Intracellular signaling
ATP is involved in signal transduction by serving as substrate for kinases, enzymes that transfer phosphate groups. Kinases are the most common ATP-binding proteins. They share a small number of common folds. Phosphorylation of a protein by a kinase can activate a cascade such as the mitogen-activated protein kinase cascade. | Adenosine triphosphate | Wikipedia | 510 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
ATP is also a substrate of adenylate cyclase, most commonly in G protein-coupled receptor signal transduction pathways and is transformed to second messenger, cyclic AMP, which is involved in triggering calcium signals by the release of calcium from intracellular stores. This form of signal transduction is particularly important in brain function, although it is involved in the regulation of a multitude of other cellular processes.
DNA and RNA synthesis
ATP is one of four monomers required in the synthesis of RNA. The process is promoted by RNA polymerases. A similar process occurs in the formation of DNA, except that ATP is first converted to the deoxyribonucleotide dATP. Like many condensation reactions in nature, DNA replication and DNA transcription also consume ATP.
Amino acid activation in protein synthesis
Aminoacyl-tRNA synthetase enzymes consume ATP in the attachment tRNA to amino acids, forming aminoacyl-tRNA complexes. Aminoacyl transferase binds AMP-amino acid to tRNA. The coupling reaction proceeds in two steps:
aa + ATP ⟶ aa-AMP + PPi
aa-AMP + tRNA ⟶ aa-tRNA + AMP
The amino acid is coupled to the penultimate nucleotide at the 3′-end of the tRNA (the A in the sequence CCA) via an ester bond (roll over in illustration).
ATP binding cassette transporter
Transporting chemicals out of a cell against a gradient is often associated with ATP hydrolysis. Transport is mediated by ATP binding cassette transporters. The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.
Extracellular signalling and neurotransmission
Cells secrete ATP to communicate with other cells in a process called purinergic signalling. ATP serves as a neurotransmitter in many parts of the nervous system, modulates ciliary beating, affects vascular oxygen supply etc. ATP is either secreted directly across the cell membrane through channel proteins or is pumped into vesicles which then fuse with the membrane. Cells detect ATP using the purinergic receptor proteins P2X and P2Y. ATP has been shown to be a critically important signalling molecule for microglia - neuron interactions in the adult brain, as well as during brain development. Furthermore, tissue-injury induced ATP-signalling is a major factor in rapid microglial phenotype changes. | Adenosine triphosphate | Wikipedia | 493 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
Muscle contraction
ATP fuels muscle contractions. Muscle contractions are regulated by signaling pathways, although different muscle types being regulated by specific pathways and stimuli based on their particular function. However, in all muscle types, contraction is performed by the proteins actin and myosin.
ATP is initially bound to myosin. When ATPase hydrolyzes the bound ATP into ADP and inorganic phosphate, myosin is positioned in a way that it can bind to actin. Myosin bound by ADP and Pi forms cross-bridges with actin and the subsequent release of ADP and Pi releases energy as the power stroke. The power stroke causes actin filament to slide past the myosin filament, shortening the muscle and causing a contraction. Another ATP molecule can then bind to myosin, releasing it from actin and allowing this process to repeat.
Protein solubility
ATP has recently been proposed to act as a biological hydrotrope and has been shown to affect proteome-wide solubility.
Abiogenic origins
Acetyl phosphate (AcP), a precursor to ATP, can readily be synthesized at modest yields from thioacetate in pH 7 and 20 °C and pH 8 and 50 °C, although acetyl phosphate is less stable in warmer temperatures and alkaline conditions than in cooler and acidic to neutral conditions. It is unable to promote polymerization of ribonucleotides and amino acids and was only capable of phosphorylation of organic compounds. It was shown that it can promote aggregation and stabilization of AMP in the presence of Na+, aggregation of nucleotides could promote polymerization above 75 °C in the absence of Na+. It is possible that polymerization promoted by AcP could occur at mineral surfaces. It was shown that ADP can only be phosphorylated to ATP by AcP and other nucleoside triphosphates were not phosphorylated by AcP. This might explain why all lifeforms use ATP to drive biochemical reactions.
ATP analogues
Biochemistry laboratories often use in vitro studies to explore ATP-dependent molecular processes. ATP analogs are also used in X-ray crystallography to determine a protein structure in complex with ATP, often together with other substrates.
Enzyme inhibitors of ATP-dependent enzymes such as kinases are needed to examine the binding sites and transition states involved in ATP-dependent reactions. | Adenosine triphosphate | Wikipedia | 495 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
Most useful ATP analogs cannot be hydrolyzed as ATP would be; instead, they trap the enzyme in a structure closely related to the ATP-bound state. Adenosine 5′-(γ-thiotriphosphate) is an extremely common ATP analog in which one of the gamma-phosphate oxygens is replaced by a sulfur atom; this anion is hydrolyzed at a dramatically slower rate than ATP itself and functions as an inhibitor of ATP-dependent processes. In crystallographic studies, hydrolysis transition states are modeled by the bound vanadate ion.
Caution is warranted in interpreting the results of experiments using ATP analogs, since some enzymes can hydrolyze them at appreciable rates at high concentration.
Medical use
ATP is used intravenously for some heart related conditions.
History
ATP was discovered in 1929 by and Jendrassik and, independently, by Cyrus Fiske and Yellapragada Subba Rao of Harvard Medical School, both teams competing against each other to find an assay for phosphorus.
It was proposed to be the intermediary between energy-yielding and energy-requiring reactions in cells by Fritz Albert Lipmann in 1941.
It was first synthesized in the laboratory by Alexander Todd in 1948, and he was awarded the Nobel Prize in Chemistry in 1957 partly for this work.
The 1978 Nobel Prize in Chemistry was awarded to Peter Dennis Mitchell for the discovery of the chemiosmotic mechanism of ATP synthesis.
The 1997 Nobel Prize in Chemistry was divided, one half jointly to Paul D. Boyer and John E. Walker "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)" and the other half to Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase." | Adenosine triphosphate | Wikipedia | 376 | 1800 | https://en.wikipedia.org/wiki/Adenosine%20triphosphate | Biology and health sciences | Biochemistry and molecular biology | null |
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza. Drugs which inhibit growth of viruses are termed antiviral drugs or antivirals. Antibiotics are also not effective against fungi. Drugs which inhibit growth of fungi are called antifungal drugs.
Sometimes, the term antibiotic—literally "opposing life", from the Greek roots ἀντι anti, "against" and βίος bios, "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antiseptics) are fully synthetic. However, both classes have the same effect of killing or preventing the growth of microorganisms, and both are included in antimicrobial chemotherapy. "Antibacterials" include bactericides, bacteriostatics, antibacterial soaps, and chemical disinfectants, whereas antibiotics are an important class of antibacterials used more specifically in medicine and sometimes in livestock feed. | Antibiotic | Wikipedia | 321 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibiotics have been used since ancient times. Many civilizations used topical application of moldy bread, with many references to its beneficial effects arising from ancient Egypt, Nubia, China, Serbia, Greece, and Rome. The first person to directly document the use of molds to treat infections was John Parkinson (1567–1650). Antibiotics revolutionized medicine in the 20th century. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Alexander Fleming (1881–1955) discovered modern day penicillin in 1928, the widespread use of which proved significantly beneficial during wartime. The first sulfonamide and the first systemically active antibacterial drug, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 or 1933 at the Bayer Laboratories of the IG Farben conglomerate in Germany. However, the effectiveness and easy access to antibiotics have also led to their overuse and some bacteria have evolved resistance to them. Antimicrobial resistance (AMR), a naturally occurring process, is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. The World Health Organization has classified AMR as a widespread "serious threat [that] is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country". Each year, nearly 5 million deaths are associated with AMR globally. Global deaths attributable to AMR numbered 1.27 million in 2019.
Etymology
The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs. Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis. These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1947. | Antibiotic | Wikipedia | 451 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. In current usage, the term "antibiotic" is applied to any medication that kills bacteria or inhibits their growth, regardless of whether that medication is produced by a microorganism or not.
The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for life, lively", which comes from βίωσις (biōsis), "way of life", and that from βίος (bios), "life". The term "antibacterial" derives from Greek ἀντί (anti), "against" + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane", because the first bacteria to be discovered were rod-shaped.
Usage
Medical uses
Antibiotics are used to treat or prevent bacterial infections, and sometimes protozoan infections. (Metronidazole is effective against a number of parasitic diseases). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an empiric therapy is adopted. This involves the administration of a broad-spectrum antibiotic based on the signs and symptoms presented and is initiated pending laboratory results that can take several days.
When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance. To avoid surgery, antibiotics may be given for non-complicated acute appendicitis. | Antibiotic | Wikipedia | 472 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibiotics may be given as a preventive measure and this is usually limited to at-risk populations such as those with a weakened immune system (particularly in HIV cases to prevent pneumonia), those taking immunosuppressive drugs, cancer patients, and those having surgery. Their use in surgical procedures is to help prevent infection of incisions. They have an important role in dental antibiotic prophylaxis where their use may prevent bacteremia and consequent infective endocarditis. Antibiotics are also used to prevent infection in cases of neutropenia particularly cancer-related.
The use of antibiotics for secondary prevention of coronary heart disease is not supported by current scientific evidence, and may actually increase cardiovascular mortality, all-cause mortality and the occurrence of stroke.
Routes of administration
There are many different routes of administration for antibiotic treatment. Antibiotics are usually taken by mouth. In more severe cases, particularly deep-seated systemic infections, antibiotics can be given intravenously or by injection. Where the site of infection is easily accessed, antibiotics may be given topically in the form of eye drops onto the conjunctiva for conjunctivitis or ear drops for ear infections and acute cases of swimmer's ear. Topical use is also one of the treatment options for some skin conditions including acne and cellulitis. Advantages of topical application include achieving high and sustained concentration of antibiotic at the site of infection; reducing the potential for systemic absorption and toxicity, and total volumes of antibiotic required are reduced, thereby also reducing the risk of antibiotic misuse. Topical antibiotics applied over certain types of surgical wounds have been reported to reduce the risk of surgical site infections. However, there are certain general causes for concern with topical administration of antibiotics. Some systemic absorption of the antibiotic may occur; the quantity of antibiotic applied is difficult to accurately dose, and there is also the possibility of local hypersensitivity reactions or contact dermatitis occurring. It is recommended to administer antibiotics as soon as possible, especially in life-threatening infections. Many emergency departments stock antibiotics for this purpose. | Antibiotic | Wikipedia | 426 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Global consumption
Antibiotic consumption varies widely between countries. The WHO report on surveillance of antibiotic consumption published in 2018 analysed 2015 data from 65 countries. As measured in defined daily doses per 1,000 inhabitants per day. Mongolia had the highest consumption with a rate of 64.4. Burundi had the lowest at 4.4. Amoxicillin and amoxicillin/clavulanic acid were the most frequently consumed.
Side effects
Antibiotics are screened for any negative effects before their approval for clinical use, and are usually considered safe and well tolerated. However, some antibiotics have been associated with a wide extent of adverse side effects ranging from mild to very severe depending on the type of antibiotic used, the microbes targeted, and the individual patient. Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity or allergic reactions. Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis.
Common side effects of oral antibiotics include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridioides difficile. Taking probiotics during the course of antibiotic treatment can help prevent antibiotic-associated diarrhea. Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area. Additional side effects can result from interaction with other drugs, such as the possibility of tendon damage from the administration of a quinolone antibiotic with a systemic corticosteroid.
Some antibiotics may also damage the mitochondrion, a bacteria-derived organelle found in eukaryotic, including human, cells. Mitochondrial damage cause oxidative stress in cells and has been suggested as a mechanism for side effects from fluoroquinolones. They are also known to affect chloroplasts.
Interactions | Antibiotic | Wikipedia | 418 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Birth control pills
There are few well-controlled studies on whether antibiotic use increases the risk of oral contraceptive failure. The majority of studies indicate antibiotics do not interfere with birth control pills, such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). Situations that may increase the risk of oral contraceptive failure include non-compliance (missing taking the pill), vomiting, or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting ethinylestradiol serum levels in the blood. Women with menstrual irregularities may be at higher risk of failure and should be advised to use backup contraception during antibiotic treatment and for one week after its completion. If patient-specific risk factors for reduced oral contraceptive efficacy are suspected, backup contraception is recommended.
In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic rifampicin, these cases may be due to an increase in the activities of hepatic liver enzymes' causing increased breakdown of the pill's active ingredients. Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial. Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral contraceptives. More studies on the possible interactions between antibiotics and birth control pills (oral contraceptives) are required as well as careful assessment of patient-specific risk factors for potential oral contractive pill failure prior to dismissing the need for backup contraception.
Alcohol
Interactions between alcohol and certain antibiotics may occur and may cause side effects and decreased effectiveness of antibiotic therapy. While moderate alcohol consumption is unlikely to interfere with many common antibiotics, there are specific types of antibiotics with which alcohol consumption may cause serious side effects. Therefore, potential risks of side effects and effectiveness depend on the type of antibiotic administered. | Antibiotic | Wikipedia | 417 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibiotics such as metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase, which may result in vomiting, nausea, and shortness of breath. In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption. Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.
Pharmacodynamics
The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. The bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells. These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection. Since the activity of antibacterials depends frequently on its concentration, in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial.
To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile, and several pharmacological parameters are used as markers of drug efficacy.
Combination therapy | Antibiotic | Wikipedia | 340 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
In important infectious diseases, including tuberculosis, combination therapy (i.e., the concurrent application of two or more antibiotics) has been used to delay or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their synergistic effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect. Fosfomycin has the highest number of synergistic combinations among antibiotics and is almost always used as a partner drug. Methicillin-resistant Staphylococcus aureus infections may be treated with a combination therapy of fusidic acid and rifampicin. Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if one of the antibiotics was given as a monotherapy. For example, chloramphenicol and tetracyclines are antagonists to penicillins. However, this can vary depending on the species of bacteria. In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic.
In addition to combining one antibiotic with another, antibiotics are sometimes co-administered with resistance-modifying agents. For example, β-lactam antibiotics may be used in combination with β-lactamase inhibitors, such as clavulanic acid or sulbactam, when a patient is infected with a β-lactamase-producing strain of bacteria.
Classes | Antibiotic | Wikipedia | 302 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities, killing the bacteria. Protein synthesis inhibitors (macrolides, lincosamides, and tetracyclines) are usually bacteriostatic, inhibiting further growth (with the exception of bactericidal aminoglycosides). Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as gram-negative or gram-positive, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year break in discovering classes of antibacterial compounds, four new classes of antibiotics were introduced to clinical use in the late 2000s and early 2010s: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such as linezolid), and lipiarmycins (such as fidaxomicin).
Production
With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds. These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 1000 daltons.
Since the first pioneering efforts of Howard Florey and Chain in 1939, the importance of antibiotics, including antibacterials, to medicine has led to intense research into producing antibacterials at large scales. Following screening of antibacterials against a wide range of bacteria, production of the active compounds is carried out using fermentation, usually in strongly aerobic conditions.
Resistance | Antibiotic | Wikipedia | 508 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antimicrobial resistance (AMR or AR) is a naturally occurring process. AMR is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. The emergence of antibiotic-resistant bacteria is a common phenomenon mainly caused by the overuse/misuse. It represents a threat to health globally. Each year, nearly 5 million deaths are associated with AMR globally.
Emergence of resistance often reflects evolutionary processes that take place during antibiotic therapy. The antibiotic treatment may select for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibiotics. Under certain conditions, it may result in preferential growth of resistant bacteria, while growth of susceptible bacteria is inhibited by the drug. For example, antibacterial selection for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment. Antibiotics such as penicillin and erythromycin, which used to have a high efficacy against many bacterial species and strains, have become less effective, due to the increased resistance of many bacterial strains.
Resistance may take the form of biodegradation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces.
The survival of bacteria often results from an inheritable resistance, but the growth of resistance to antibacterials also occurs through horizontal gene transfer. Horizontal transfer is more likely to happen in locations of frequent antibiotic use.
Antibacterial resistance may impose a biological cost, thereby reducing fitness of resistant strains, which can limit the spread of antibacterial-resistant bacteria, for example, in the absence of antibacterial compounds. Additional mutations, however, may compensate for this fitness cost and can aid the survival of these bacteria.
Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms. Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability. | Antibiotic | Wikipedia | 428 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains. For example, an antibiotic target may be absent from the bacterial genome. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA. Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains. The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange. For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes. Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials. Cross-resistance to several antibacterials may also occur when a resistance mechanism encoded by a single gene conveys resistance to more than one antibacterial compound.
Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases that were, for a while, well controlled. For example, emergent bacterial strains causing tuberculosis that are resistant to previously effective antibacterial treatments pose many therapeutic challenges. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials. The United Kingdom's Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections." On 26 May 2016, an E. coli "superbug" was identified in the United States resistant to colistin, "the last line of defence" antibiotic.
In recent years, even anaerobic bacteria, historically considered less concerning in terms of resistance, have demonstrated high rates of antibiotic resistance, particularly Bacteroides, for which resistance rates to penicillin have been reported to exceed 90%.
Misuse | Antibiotic | Wikipedia | 457 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Per The ICU Book, "The first rule of antibiotics is to try not to use them, and the second rule is try not to use too many of them." Inappropriate antibiotic treatment and overuse of antibiotics have contributed to the emergence of antibiotic-resistant bacteria. However, potential harm from antibiotics extends beyond selection of antimicrobial resistance and their overuse is associated with adverse effects for patients themselves, seen most clearly in critically ill patients in Intensive care units. Self-prescribing of antibiotics is an example of misuse. Many antibiotics are frequently prescribed to treat symptoms or diseases that do not respond to antibiotics or that are likely to resolve without treatment. Also, incorrect or suboptimal antibiotics are prescribed for certain bacterial infections. The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s. Widespread usage of antibiotics in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibiotics.
Common forms of antibiotic misuse include excessive use of prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibiotics on the basis of the patient's weight and history of prior use. Other forms of misuse include failure to take the entire prescribed course of the antibiotic, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the common cold. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them". Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics. The lack of rapid point of care diagnostic tests, particularly in resource-limited settings is considered one of the drivers of antibiotic misuse. | Antibiotic | Wikipedia | 380 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics. The issues of misuse and overuse of antibiotics have been addressed by the formation of the US Interagency Task Force on Antimicrobial Resistance. This task force aims to actively address antimicrobial resistance, and is coordinated by the US Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and the National Institutes of Health, as well as other US agencies. A non-governmental organization campaign group is Keep Antibiotics Working. In France, an "Antibiotics are not automatic" government campaign started in 2002 and led to a marked reduction of unnecessary antibiotic prescriptions, especially in children.
The emergence of antibiotic resistance has prompted restrictions on their use in the UK in 1970 (Swann report 1969), and the European Union has banned the use of antibiotics as growth-promotional agents since 2003. Moreover, several organizations (including the World Health Organization, the National Academy of Sciences, and the U.S. Food and Drug Administration) have advocated restricting the amount of antibiotic use in food animal production. However, commonly there are delays in regulatory and legislative actions to limit the use of antibiotics, attributable partly to resistance against such regulation by industries using or selling antibiotics, and to the time required for research to test causal links between their use and resistance to them. Two federal bills (S.742 and H.R. 2562) aimed at phasing out nontherapeutic use of antibiotics in US food animals were proposed, but have not passed. These bills were endorsed by public health and medical organizations, including the American Holistic Nurses' Association, the American Medical Association, and the American Public Health Association.
Despite pledges by food companies and restaurants to reduce or eliminate meat that comes from animals treated with antibiotics, the purchase of antibiotics for use on farm animals has been increasing every year.
There has been extensive use of antibiotics in animal husbandry. In the United States, the question of emergence of antibiotic-resistant bacterial strains due to use of antibiotics in livestock was raised by the US Food and Drug Administration (FDA) in 1977. In March 2012, the United States District Court for the Southern District of New York, ruling in an action brought by the Natural Resources Defense Council and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock, which violated FDA regulations. | Antibiotic | Wikipedia | 493 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.
Other forms of antibiotic-associated harm include anaphylaxis, drug toxicity most notably kidney and liver damage, and super-infections with resistant organisms. Antibiotics are also known to affect mitochondrial function, and this may contribute to the bioenergetic failure of immune cells seen in sepsis. They also alter the microbiome of the gut, lungs, and skin, which may be associated with adverse effects such as Clostridioides difficile associated diarrhoea. Whilst antibiotics can clearly be lifesaving in patients with bacterial infections, their overuse, especially in patients where infections are hard to diagnose, can lead to harm via multiple mechanisms.
History
Before the early 20th century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2,000 years ago. Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials to treat infections. Nubian mummies studied in the 1990s were found to contain significant levels of tetracycline. The beer brewed at that time was conjectured to have been the source.
The use of antibiotics in modern medicine began with the discovery of synthetic antibiotics derived from dyes. Various Essential oils have been shown to have anti-microbial properties. Along with this, the plants from which these oils have been derived can be used as niche anti-microbial agents.
Synthetic antibiotics derived from dyes
Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Ehrlich noted certain dyes would colour human, animal, or bacterial cells, whereas others did not. He then proposed the idea that it might be possible to create chemicals that would act as a selective drug that would bind to and kill bacteria without harming the human host. After screening hundreds of dyes against various organisms, in 1907, he discovered a medicinally useful drug, the first synthetic antibacterial organoarsenic compound salvarsan, now called arsphenamine. | Antibiotic | Wikipedia | 456 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
This heralded the era of antibacterial treatment that was begun with the discovery of a series of arsenic-derived synthetic antibiotics by both Alfred Bertheim and Ehrlich in 1907. Ehrlich and Bertheim had experimented with various chemicals derived from dyes to treat trypanosomiasis in mice and spirochaeta infection in rabbits. While their early compounds were too toxic, Ehrlich and Sahachiro Hata, a Japanese bacteriologist working with Ehrlich in the quest for a drug to treat syphilis, achieved success with the 606th compound in their series of experiments. In 1910, Ehrlich and Hata announced their discovery, which they called drug "606", at the Congress for Internal Medicine at Wiesbaden. The Hoechst company began to market the compound toward the end of 1910 under the name Salvarsan, now known as arsphenamine. The drug was used to treat syphilis in the first half of the 20th century. In 1908, Ehrlich received the Nobel Prize in Physiology or Medicine for his contributions to immunology. Hata was nominated for the Nobel Prize in Chemistry in 1911 and for the Nobel Prize in Physiology or Medicine in 1912 and 1913.
The first sulfonamide and the first systemically active antibacterial drug, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 or 1933 at the Bayer Laboratories of the IG Farben conglomerate in Germany, for which Domagk received the 1939 Nobel Prize in Physiology or Medicine. Sulfanilamide, the active drug of Prontosil, was not patentable as it had already been in use in the dye industry for some years. Prontosil had a relatively broad effect against Gram-positive cocci, but not against enterobacteria. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug opened the era of antibacterials.
Penicillin and other natural antibiotics
Observations about the growth of some microorganisms inhibiting the growth of other microorganisms have been reported since the late 19th century. These observations of antibiosis between microorganisms led to the discovery of natural antibacterials. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics". | Antibiotic | Wikipedia | 497 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
In 1874, physician Sir William Roberts noted that cultures of the mould Penicillium glaucum that is used in the making of some types of blue cheese did not display bacterial contamination.
In 1895 Vincenzo Tiberio, Italian physician, published a paper on the antibacterial power of some extracts of mold.
In 1897, doctoral student Ernest Duchesne submitted a dissertation, "" (Contribution to the study of vital competition in micro-organisms: antagonism between moulds and microbes), the first known scholarly work to consider the therapeutic capabilities of moulds resulting from their anti-microbial activity. In his thesis, Duchesne proposed that bacteria and moulds engage in a perpetual battle for survival. Duchesne observed that E. coli was eliminated by Penicillium glaucum when they were both grown in the same culture. He also observed that when he inoculated laboratory animals with lethal doses of typhoid bacilli together with Penicillium glaucum, the animals did not contract typhoid. Duchesne's army service after getting his degree prevented him from doing any further research. Duchesne died of tuberculosis, a disease now treated by antibiotics.
In 1928, Sir Alexander Fleming postulated the existence of penicillin, a molecule produced by certain moulds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of disease-causing bacteria when he noticed the spores of a green mold, Penicillium rubens, in one of his culture plates. He observed that the presence of the mould killed or prevented the growth of the bacteria. Fleming postulated that the mould must secrete an antibacterial substance, which he named penicillin in 1928. Fleming believed that its antibacterial properties could be exploited for chemotherapy. He initially characterised some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists. | Antibiotic | Wikipedia | 418 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Ernst Chain, Howard Florey and Edward Abraham succeeded in purifying the first penicillin, penicillin G, in 1942, but it did not become widely available outside the Allied military before 1945. Later, Norman Heatley developed the back extraction technique for efficiently purifying penicillin in bulk. The chemical structure of penicillin was first proposed by Abraham in 1942 and then later confirmed by Dorothy Crowfoot Hodgkin in 1945. Purified penicillin displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in humans. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic sulfonamides. (see below) The development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety. For their successful development of penicillin, which Fleming had accidentally discovered but could not develop himself, as a therapeutic drug, Chain and Florey shared the 1945 Nobel Prize in Medicine with Fleming.
Florey credited René Dubos with pioneering the approach of deliberately and systematically searching for antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's research in penicillin. In 1939, coinciding with the start of World War II, Dubos had reported the discovery of the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and 80% tyrocidine, from Bacillus brevis. It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II. Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also proved too toxic for systemic usage. Research results obtained during that period were not shared between the Axis and the Allied powers during World War II and limited access during the Cold War.
Late 20th century
During the mid-20th century, the number of new antibiotic substances introduced for medical use increased significantly. From 1935 to 1968, 12 new classes were launched. However, after this, the number of new classes dropped markedly, with only two new classes introduced between 1969 and 2003. | Antibiotic | Wikipedia | 453 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibiotic pipeline
Both the WHO and the Infectious Disease Society of America report that the weak antibiotic pipeline does not match bacteria's increasing ability to develop resistance. The Infectious Disease Society of America report noted that the number of new antibiotics approved for marketing per year had been declining and identified seven antibiotics against the Gram-negative bacilli currently in phase 2 or phase 3 clinical trials. However, these drugs did not address the entire spectrum of resistance of Gram-negative bacilli. According to the WHO fifty one new therapeutic entities - antibiotics (including combinations), are in phase 1–3 clinical trials as of May 2017. Antibiotics targeting multidrug-resistant Gram-positive pathogens remains a high priority.
A few antibiotics have received marketing authorization in the last seven years. The cephalosporin ceftaroline and the lipoglycopeptides oritavancin and telavancin have been approved for the treatment of acute bacterial skin and skin structure infection and community-acquired bacterial pneumonia. The lipoglycopeptide dalbavancin and the oxazolidinone tedizolid has also been approved for use for the treatment of acute bacterial skin and skin structure infection. The first in a new class of narrow-spectrum macrocyclic antibiotics, fidaxomicin, has been approved for the treatment of C. difficile colitis. New cephalosporin-lactamase inhibitor combinations also approved include ceftazidime-avibactam and ceftolozane-avibactam for complicated urinary tract infection and intra-abdominal infection. | Antibiotic | Wikipedia | 330 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor. In the US, the Antibiotic Development to Advance Patient Treatment (ADAPT) Act was introduced with the aim of fast tracking the drug development of antibiotics to combat the growing threat of 'superbugs'. Under this Act, FDA can approve antibiotics and antifungals treating life-threatening infections based on smaller clinical trials. The CDC will monitor the use of antibiotics and the emerging resistance, and publish the data. The FDA antibiotics labeling process, 'Susceptibility Test Interpretive Criteria for Microbial Organisms' or 'breakpoints', will provide accurate data to healthcare professionals. According to Allan Coukell, senior director for health programs at The Pew Charitable Trusts, "By allowing drug developers to rely on smaller datasets, and clarifying FDA's authority to tolerate a higher level of uncertainty for these drugs when making a risk/benefit calculation, ADAPT would make the clinical trials more feasible."
Replenishing the antibiotic pipeline and developing other new therapies
Because antibiotic-resistant bacterial strains continue to emerge and spread, there is a constant need to develop new antibacterial treatments. Current strategies include traditional chemistry-based approaches such as natural product-based drug discovery, newer chemistry-based approaches such as drug design, traditional biology-based approaches such as immunoglobulin therapy, and experimental biology-based approaches such as phage therapy, fecal microbiota transplants, antisense RNA-based treatments, and CRISPR-Cas9-based treatments.
Natural product-based antibiotic discovery
Most of the antibiotics in current use are natural products or natural product derivatives, and bacterial, fungal, plant and animal extracts are being screened in the search for new antibiotics. Organisms may be selected for testing based on ecological, ethnomedical, genomic, or historical rationales. Medicinal plants, for example, are screened on the basis that they are used by traditional healers to prevent or cure infection and may therefore contain antibacterial compounds. Also, soil bacteria are screened on the basis that, historically, they have been a very rich source of antibiotics (with 70 to 80% of antibiotics in current use derived from the actinomycetes). | Antibiotic | Wikipedia | 474 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
In addition to screening natural products for direct antibacterial activity, they are sometimes screened for the ability to suppress antibiotic resistance and antibiotic tolerance. For example, some secondary metabolites inhibit drug efflux pumps, thereby increasing the concentration of antibiotic able to reach its cellular target and decreasing bacterial resistance to the antibiotic. Natural products known to inhibit bacterial efflux pumps include the alkaloid lysergol, the carotenoids capsanthin and capsorubin, and the flavonoids rotenone and chrysin. Other natural products, this time primary metabolites rather than secondary metabolites, have been shown to eradicate antibiotic tolerance. For example, glucose, mannitol, and fructose reduce antibiotic tolerance in Escherichia coli and Staphylococcus aureus, rendering them more susceptible to killing by aminoglycoside antibiotics.
Natural products may be screened for the ability to suppress bacterial virulence factors too. Virulence factors are molecules, cellular structures and regulatory systems that enable bacteria to evade the body's immune defenses (e.g. urease, staphyloxanthin), move towards, attach to, and/or invade human cells (e.g. type IV pili, adhesins, internalins), coordinate the activation of virulence genes (e.g. quorum sensing), and cause disease (e.g. exotoxins). Examples of natural products with antivirulence activity include the flavonoid epigallocatechin gallate (which inhibits listeriolysin O), the quinone tetrangomycin (which inhibits staphyloxanthin), and the sesquiterpene zerumbone (which inhibits Acinetobacter baumannii motility).
Immunoglobulin therapy | Antibiotic | Wikipedia | 396 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Antibodies (anti-tetanus immunoglobulin) have been used in the treatment and prevention of tetanus since the 1910s, and this approach continues to be a useful way of controlling bacterial diseases. The monoclonal antibody bezlotoxumab, for example, has been approved by the US FDA and EMA for recurrent Clostridioides difficile infection, and other monoclonal antibodies are in development (e.g. AR-301 for the adjunctive treatment of S. aureus ventilator-associated pneumonia). Antibody treatments act by binding to and neutralizing bacterial exotoxins and other virulence factors.
Phage therapy
Phage therapy is under investigation as a method of treating antibiotic-resistant strains of bacteria. Phage therapy involves infecting bacterial pathogens with viruses. Bacteriophages and their host ranges are extremely specific for certain bacteria, thus, unlike antibiotics, they do not disturb the host organism's intestinal microbiota. Bacteriophages, also known as phages, infect and kill bacteria primarily during lytic cycles. Phages insert their DNA into the bacterium, where it is transcribed and used to make new phages, after which the cell will lyse, releasing new phage that are able to infect and destroy further bacteria of the same strain. The high specificity of phage protects "good" bacteria from destruction.
Some disadvantages to the use of bacteriophages also exist, however. Bacteriophages may harbour virulence factors or toxic genes in their genomes and, prior to use, it may be prudent to identify genes with similarity to known virulence factors or toxins by genomic sequencing. In addition, the oral and IV administration of phages for the eradication of bacterial infections poses a much higher safety risk than topical application. Also, there is the additional concern of uncertain immune responses to these large antigenic cocktails.
There are considerable regulatory hurdles that must be cleared for such therapies. Despite numerous challenges, the use of bacteriophages as a replacement for antimicrobial agents against MDR pathogens that no longer respond to conventional antibiotics, remains an attractive option.
Fecal microbiota transplants | Antibiotic | Wikipedia | 470 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Fecal microbiota transplants involve transferring the full intestinal microbiota from a healthy human donor (in the form of stool) to patients with C. difficile infection. Although this procedure has not been officially approved by the US FDA, its use is permitted under some conditions in patients with antibiotic-resistant C. difficile infection. Cure rates are around 90%, and work is underway to develop stool banks, standardized products, and methods of oral delivery. Fecal microbiota transplantation has also been used more recently for inflammatory bowel diseases.
Antisense RNA-based treatments
Antisense RNA-based treatment (also known as gene silencing therapy) involves (a) identifying bacterial genes that encode essential proteins (e.g. the Pseudomonas aeruginosa genes acpP, lpxC, and rpsJ), (b) synthesizing single-stranded RNA that is complementary to the mRNA encoding these essential proteins, and (c) delivering the single-stranded RNA to the infection site using cell-penetrating peptides or liposomes. The antisense RNA then hybridizes with the bacterial mRNA and blocks its translation into the essential protein. Antisense RNA-based treatment has been shown to be effective in in vivo models of P. aeruginosa pneumonia.
In addition to silencing essential bacterial genes, antisense RNA can be used to silence bacterial genes responsible for antibiotic resistance. For example, antisense RNA has been developed that silences the S. aureus mecA gene (the gene that encodes modified penicillin-binding protein 2a and renders S. aureus strains methicillin-resistant). Antisense RNA targeting mecA mRNA has been shown to restore the susceptibility of methicillin-resistant staphylococci to oxacillin in both in vitro and in vivo studies.
CRISPR-Cas9-based treatments
In the early 2000s, a system was discovered that enables bacteria to defend themselves against invading viruses. The system, known as CRISPR-Cas9, consists of (a) an enzyme that destroys DNA (the nuclease Cas9) and (b) the DNA sequences of previously encountered viral invaders (CRISPR). These viral DNA sequences enable the nuclease to target foreign (viral) rather than self (bacterial) DNA. | Antibiotic | Wikipedia | 492 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Although the function of CRISPR-Cas9 in nature is to protect bacteria, the DNA sequences in the CRISPR component of the system can be modified so that the Cas9 nuclease targets bacterial resistance genes or bacterial virulence genes instead of viral genes. The modified CRISPR-Cas9 system can then be administered to bacterial pathogens using plasmids or bacteriophages. This approach has successfully been used to silence antibiotic resistance and reduce the virulence of enterohemorrhagic E. coli in an in vivo model of infection.
Reducing the selection pressure for antibiotic resistance
In addition to developing new antibacterial treatments, it is important to reduce the selection pressure for the emergence and spread of antimicrobial resistance (AMR), such as antibiotic resistance. Strategies to accomplish this include well-established infection control measures such as infrastructure improvement (e.g. less crowded housing), better sanitation (e.g. safe drinking water and food), better use of vaccines and vaccine development, other approaches such as antibiotic stewardship, and experimental approaches such as the use of prebiotics and probiotics to prevent infection. Antibiotic cycling, where antibiotics are alternated by clinicians to treat microbial diseases, is proposed, but recent studies revealed such strategies are ineffective against antibiotic resistance.
Vaccines
Vaccines are an essential part of the response to reduce AMR as they prevent infections, reduce the use and overuse of antimicrobials, and slow the emergence and spread of drug-resistant pathogens. Vaccination either excites or reinforces the immune competence of a host to ward off infection, leading to the activation of macrophages, the production of antibodies, inflammation, and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases. | Antibiotic | Wikipedia | 379 | 1805 | https://en.wikipedia.org/wiki/Antibiotic | Biology and health sciences | Drugs and medication | null |
Allotropy or allotropism () is the property of some chemical elements to exist in two or more different forms, in the same physical state, known as allotropes of the elements. Allotropes are different structural modifications of an element: the atoms of the element are bonded together in different manners.
For example, the allotropes of carbon include diamond (the carbon atoms are bonded together to form a cubic lattice of tetrahedra), graphite (the carbon atoms are bonded together in sheets of a hexagonal lattice), graphene (single sheets of graphite), and fullerenes (the carbon atoms are bonded together in spherical, tubular, or ellipsoidal formations).
The term allotropy is used for elements only, not for compounds. The more general term, used for any compound, is polymorphism, although its use is usually restricted to solid materials such as crystals. Allotropy refers only to different forms of an element within the same physical phase (the state of matter, such as a solid, liquid or gas). The differences between these states of matter would not alone constitute examples of allotropy. Allotropes of chemical elements are frequently referred to as polymorphs or as phases of the element.
For some elements, allotropes have different molecular formulae or different crystalline structures, as well as a difference in physical phase; for example, two allotropes of oxygen (dioxygen, O2, and ozone, O3) can both exist in the solid, liquid and gaseous states. Other elements do not maintain distinct allotropes in different physical phases; for example, phosphorus has numerous solid allotropes, which all revert to the same P4 form when melted to the liquid state.
History
The concept of allotropy was originally proposed in 1840 by the Swedish scientist Baron Jöns Jakob Berzelius (1779–1848). The term is derived . After the acceptance of Avogadro's hypothesis in 1860, it was understood that elements could exist as polyatomic molecules, and two allotropes of oxygen were recognized as O2 and O3. In the early 20th century, it was recognized that other cases such as carbon were due to differences in crystal structure. | Allotropy | Wikipedia | 478 | 1839 | https://en.wikipedia.org/wiki/Allotropy | Physical sciences | Basics_4 | null |
By 1912, Ostwald noted that the allotropy of elements is just a special case of the phenomenon of polymorphism known for compounds, and proposed that the terms allotrope and allotropy be abandoned and replaced by polymorph and polymorphism. Although many other chemists have repeated this advice, IUPAC and most chemistry texts still favour the usage of allotrope and allotropy for elements only.
Differences in properties of an element's allotropes
Allotropes are different structural forms of the same element and can exhibit quite different physical properties and chemical behaviours. The change between allotropic forms is triggered by the same forces that affect other structures, i.e., pressure, light, and temperature. Therefore, the stability of the particular allotropes depends on particular conditions. For instance, iron changes from a body-centered cubic structure (ferrite) to a face-centered cubic structure (austenite) above 906 °C, and tin undergoes a modification known as tin pest from a metallic form to a semimetallic form below 13.2 °C (55.8 °F). As an example of allotropes having different chemical behaviour, ozone (O3) is a much stronger oxidizing agent than dioxygen (O2).
List of allotropes
Typically, elements capable of variable coordination number and/or oxidation states tend to exhibit greater numbers of allotropic forms. Another contributing factor is the ability of an element to catenate.
Examples of allotropes include:
Non-metals
Metalloids
Metals
Among the metallic elements that occur in nature in significant quantities (56 up to U, without Tc and Pm), almost half (27) are allotropic at ambient pressure: Li, Be, Na, Ca, Ti, Mn, Fe, Co, Sr, Y, Zr, Sn, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Yb, Hf, Tl, Th, Pa and U. Some phase transitions between allotropic forms of technologically relevant metals are those of Ti at 882 °C, Fe at 912 °C and 1,394 °C, Co at 422 °C, Zr at 863 °C, Sn at 13 °C and U at 668 °C and 776 °C. | Allotropy | Wikipedia | 496 | 1839 | https://en.wikipedia.org/wiki/Allotropy | Physical sciences | Basics_4 | null |
Most stable structure under standard conditions.
Structures stable below room temperature.
Structures stable above room temperature.
Structures stable above atmospheric pressure.
Lanthanides and actinides
Cerium, samarium, dysprosium and ytterbium have three allotropes.
Praseodymium, neodymium, gadolinium and terbium have two allotropes.
Plutonium has six distinct solid allotropes under "normal" pressures. Their densities vary within a ratio of some 4:3, which vastly complicates all kinds of work with the metal (particularly casting, machining, and storage). A seventh plutonium allotrope exists at very high pressures. The transuranium metals Np, Am, and Cm are also allotropic.
Promethium, americium, berkelium and californium have three allotropes each.
Nanoallotropes
In 2017, the concept of nanoallotropy was proposed. Nanoallotropes, or allotropes of nanomaterials, are nanoporous materials that have the same chemical composition (e.g., Au), but differ in their architecture at the nanoscale (that is, on a scale 10 to 100 times the dimensions of individual atoms). Such nanoallotropes may help create ultra-small electronic devices and find other industrial applications. The different nanoscale architectures translate into different properties, as was demonstrated for surface-enhanced Raman scattering performed on several different nanoallotropes of gold. A two-step method for generating nanoallotropes was also created. | Allotropy | Wikipedia | 343 | 1839 | https://en.wikipedia.org/wiki/Allotropy | Physical sciences | Basics_4 | null |
Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability or evidence of effectiveness. Unlike modern medicine, which employs the scientific method to test plausible therapies by way of responsible and ethical clinical trials, producing repeatable evidence of either effect or of no effect, alternative therapies reside outside of mainstream medicine and do not originate from using the scientific method, but instead rely on testimonials, anecdotes, religion, tradition, superstition, belief in supernatural "energies", pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources. Frequently used terms for relevant practices are New Age medicine, pseudo-medicine, unorthodox medicine, holistic medicine, fringe medicine, and unconventional medicine, with little distinction from quackery.
Some alternative practices are based on theories that contradict the established science of how the human body works; others appeal to the supernatural or superstitious to explain their effect or lack thereof. In others, the practice has plausibility but lacks a positive risk–benefit outcome probability. Research into alternative therapies often fails to follow proper research protocols (such as placebo-controlled trials, blind experiments and calculation of prior probability), providing invalid results. History has shown that if a method is proven to work, it eventually ceases to be alternative and becomes mainstream medicine.
Much of the perceived effect of an alternative practice arises from a belief that it will be effective, the placebo effect, or from the treated condition resolving on its own (the natural course of disease). This is further exacerbated by the tendency to turn to alternative therapies upon the failure of medicine, at which point the condition will be at its worst and most likely to spontaneously improve. In the absence of this bias, especially for diseases that are not expected to get better by themselves such as cancer or HIV infection, multiple studies have shown significantly worse outcomes if patients turn to alternative therapies. While this may be because these patients avoid effective treatment, some alternative therapies are actively harmful (e.g. cyanide poisoning from amygdalin, or the intentional ingestion of hydrogen peroxide) or actively interfere with effective treatments. | Alternative medicine | Wikipedia | 465 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
The alternative medicine sector is a highly profitable industry with a strong lobby, and faces far less regulation over the use and marketing of unproven treatments. Complementary medicine (CM), complementary and alternative medicine (CAM), integrated medicine or integrative medicine (IM), and holistic medicine attempt to combine alternative practices with those of mainstream medicine. Traditional medicine practices become "alternative" when used outside their original settings and without proper scientific explanation and evidence. Alternative methods are often marketed as more "natural" or "holistic" than methods offered by medical science, that is sometimes derogatorily called "Big Pharma" by supporters of alternative medicine. Billions of dollars have been spent studying alternative medicine, with few or no positive results and many methods thoroughly disproven.
Definitions and terminology
The terms alternative medicine, complementary medicine, integrative medicine, holistic medicine, natural medicine, unorthodox medicine, fringe medicine, unconventional medicine, and new age medicine are used interchangeably as having the same meaning and are almost synonymous in most contexts. Terminology has shifted over time, reflecting the preferred branding of practitioners. For example, the United States National Institutes of Health department studying alternative medicine, currently named the National Center for Complementary and Integrative Health (NCCIH), was established as the Office of Alternative Medicine (OAM) and was renamed the National Center for Complementary and Alternative Medicine (NCCAM) before obtaining its current name. Therapies are often framed as "natural" or "holistic", implicitly and intentionally suggesting that conventional medicine is "artificial" and "narrow in scope".
The meaning of the term "alternative" in the expression "alternative medicine", is not that it is an effective alternative to medical science (though some alternative medicine promoters may use the loose terminology to give the appearance of effectiveness). Loose terminology may also be used to suggest meaning that a dichotomy exists when it does not (e.g., the use of the expressions "Western medicine" and "Eastern medicine" to suggest that the difference is a cultural difference between the Asian east and the European west, rather than that the difference is between evidence-based medicine and treatments that do not work). | Alternative medicine | Wikipedia | 451 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Alternative medicine
Alternative medicine is defined loosely as a set of products, practices, and theories that are believed or perceived by their users to have the healing effects of medicine, but whose effectiveness has not been established using scientific methods, or whose theory and practice is not part of biomedicine, or whose theories or practices are directly contradicted by scientific evidence or scientific principles used in biomedicine. "Biomedicine" or "medicine" is that part of medical science that applies principles of biology, physiology, molecular biology, biophysics, and other natural sciences to clinical practice, using scientific methods to establish the effectiveness of that practice. Unlike medicine, an alternative product or practice does not originate from using scientific methods, but may instead be based on hearsay, religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources.
Some other definitions seek to specify alternative medicine in terms of its social and political marginality to mainstream healthcare. This can refer to the lack of support that alternative therapies receive from medical scientists regarding access to research funding, sympathetic coverage in the medical press, or inclusion in the standard medical curriculum. For example, a widely used definition devised by the US NCCIH calls it "a group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine". However, these descriptive definitions are inadequate in the present-day when some conventional doctors offer alternative medical treatments and introductory courses or modules can be offered as part of standard undergraduate medical training; alternative medicine is taught in more than half of US medical schools and US health insurers are increasingly willing to provide reimbursement for alternative therapies.
Complementary or integrative medicine
Complementary medicine (CM) or integrative medicine (IM) is when alternative medicine is used together with mainstream functional medical treatment in a belief that it improves the effect of treatments. For example, acupuncture (piercing the body with needles to influence the flow of a supernatural energy) might be believed to increase the effectiveness or "complement" science-based medicine when used at the same time. Significant drug interactions caused by alternative therapies may make treatments less effective, notably in cancer therapy. | Alternative medicine | Wikipedia | 464 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Several medical organizations differentiate between complementary and alternative medicine including the UK National Health Service (NHS), Cancer Research UK, and the US Center for Disease Control and Prevention (CDC), the latter of which states that "Complementary medicine is used in addition to standard treatments" whereas "Alternative medicine is used instead of standard treatments."
Complementary and integrative interventions are used to improve fatigue in adult cancer patients.
David Gorski has described integrative medicine as an attempt to bring pseudoscience into academic science-based medicine with skeptics such as Gorski and David Colquhoun referring to this with the pejorative term "quackademia". Robert Todd Carroll described Integrative medicine as "a synonym for 'alternative' medicine that, at its worst, integrates sense with nonsense. At its best, integrative medicine supports both consensus treatments of science-based medicine and treatments that the science, while promising perhaps, does not justify" Rose Shapiro has criticized the field of alternative medicine for rebranding the same practices as integrative medicine.
CAM is an abbreviation of the phrase complementary and alternative medicine. The 2019 World Health Organization (WHO) Global Report on Traditional and Complementary Medicine states that the terms complementary and alternative medicine "refer to a broad set of health care practices that are not part of that country's own traditional or conventional medicine and are not fully integrated into the dominant health care system. They are used interchangeably with traditional medicine in some countries."
The Integrative Medicine Exam by the American Board of Physician Specialties includes the following subjects: Manual Therapies, Biofield Therapies, Acupuncture, Movement Therapies, Expressive Arts, Traditional Chinese Medicine, Ayurveda, Indigenous Medical Systems, Homeopathic Medicine, Naturopathic Medicine, Osteopathic Medicine, Chiropractic, and Functional Medicine.
Other terms | Alternative medicine | Wikipedia | 385 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Traditional medicine (TM) refers to certain practices within a culture which have existed since before the advent of medical science, Many TM practices are based on "holistic" approaches to disease and health, versus the scientific evidence-based methods in conventional medicine. The 2019 WHO report defines traditional medicine as "the sum total of the knowledge, skill and practices based on the theories, beliefs and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness." When used outside the original setting and in the absence of scientific evidence, TM practices are typically referred to as "alternative medicine".
is another rebranding of alternative medicine. In this case, the words balance and holism are often used alongside complementary or integrative, claiming to take into fuller account the "whole" person, in contrast to the supposed reductionism of medicine.
Challenges in defining alternative medicine
Prominent members of the science and biomedical science community say that it is not meaningful to define an alternative medicine that is separate from a conventional medicine because the expressions "conventional medicine", "alternative medicine", "complementary medicine", "integrative medicine", and "holistic medicine" do not refer to any medicine at all. Others say that alternative medicine cannot be precisely defined because of the diversity of theories and practices it includes, and because the boundaries between alternative and conventional medicine overlap, are porous, and change. Healthcare practices categorized as alternative may differ in their historical origin, theoretical basis, diagnostic technique, therapeutic practice and in their relationship to the medical mainstream. Under a definition of alternative medicine as "non-mainstream", treatments considered alternative in one location may be considered conventional in another. | Alternative medicine | Wikipedia | 360 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Critics say the expression is deceptive because it implies there is an effective alternative to science-based medicine, and that complementary is deceptive because it implies that the treatment increases the effectiveness of (complements) science-based medicine, while alternative medicines that have been tested nearly always have no measurable positive effect compared to a placebo. Journalist John Diamond wrote that "there is really no such thing as alternative medicine, just medicine that works and medicine that doesn't", a notion later echoed by Paul Offit: "The truth is there's no such thing as conventional or alternative or complementary or integrative or holistic medicine. There's only medicine that works and medicine that doesn't. And the best way to sort it out is by carefully evaluating scientific studies—not by visiting Internet chat rooms, reading magazine articles, or talking to friends."
Types
Alternative medicine consists of a wide range of health care practices, products, and therapies. The shared feature is a claim to heal that is not based on the scientific method. Alternative medicine practices are diverse in their foundations and methodologies. Alternative medicine practices may be classified by their cultural origins or by the types of beliefs upon which they are based. Methods may incorporate or be based on traditional medicinal practices of a particular culture, folk knowledge, superstition, spiritual beliefs, belief in supernatural energies (antiscience), pseudoscience, errors in reasoning, propaganda, fraud, new or different concepts of health and disease, and any bases other than being proven by scientific methods. Different cultures may have their own unique traditional or belief based practices developed recently or over thousands of years, and specific practices or entire systems of practices.
Unscientific belief systems
Alternative medicine, such as using naturopathy or homeopathy in place of conventional medicine, is based on belief systems not grounded in science.
Traditional ethnic systems
Alternative medical systems may be based on traditional medicine practices, such as traditional Chinese medicine (TCM), Ayurveda in India, or practices of other cultures around the world. Some useful applications of traditional medicines have been researched and accepted within ordinary medicine, however the underlying belief systems are seldom scientific and are not accepted.
Traditional medicine is considered alternative when it is used outside its home region; or when it is used together with or instead of known functional treatment; or when it can be reasonably expected that the patient or practitioner knows or should know that it will not work – such as knowing that the practice is based on superstition. | Alternative medicine | Wikipedia | 508 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Supernatural energies
Bases of belief may include belief in existence of supernatural energies undetected by the science of physics, as in biofields, or in belief in properties of the energies of physics that are inconsistent with the laws of physics, as in energy medicine.
Herbal remedies and other substances
Substance based practices use substances found in nature such as herbs, foods, non-vitamin supplements and megavitamins, animal and fungal products, and minerals, including use of these products in traditional medical practices that may also incorporate other methods. Examples include healing claims for non-vitamin supplements, fish oil, Omega-3 fatty acid, glucosamine, echinacea, flaxseed oil, and ginseng. Herbal medicine, or phytotherapy, includes not just the use of plant products, but may also include the use of animal and mineral products. It is among the most commercially successful branches of alternative medicine, and includes the tablets, powders and elixirs that are sold as "nutritional supplements". Only a very small percentage of these have been shown to have any efficacy, and there is little regulation as to standards and safety of their contents.
Religion, faith healing, and prayer
NCCIH classification
The United States agency National Center for Complementary and Integrative Health (NCCIH) has created a classification system for branches of complementary and alternative medicine that divides them into five major groups. These groups have some overlap, and distinguish two types of energy medicine: veritable which involves scientifically observable energy (including magnet therapy, colorpuncture and light therapy) and putative, which invokes physically undetectable or unverifiable energy. None of these energies have any evidence to support that they affect the body in any positive or health promoting way. | Alternative medicine | Wikipedia | 365 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Whole medical systems: Cut across more than one of the other groups; examples include traditional Chinese medicine, naturopathy, homeopathy, and ayurveda.
Mind-body interventions: Explore the interconnection between the mind, body, and spirit, under the premise that they affect "bodily functions and symptoms". A connection between mind and body is conventional medical fact, and this classification does not include therapies with proven function such as cognitive behavioral therapy.
"Biology"-based practices: Use substances found in nature such as herbs, foods, vitamins, and other natural substances. (As used here, "biology" does not refer to the science of biology, but is a usage newly coined by NCCIH in the primary source used for this article. "Biology-based" as coined by NCCIH may refer to chemicals from a nonbiological source, such as use of the poison lead in traditional Chinese medicine, and to other nonbiological substances.)
Manipulative and body-based practices: feature manipulation or movement of body parts, such as is done in bodywork, chiropractic, and osteopathic manipulation.
Energy medicine: is a domain that deals with putative and verifiable energy fields:
Biofield therapies are intended to influence energy fields that are purported to surround and penetrate the body. The existence of such energy fields have been disproven.
Bioelectromagnetic-based therapies use verifiable electromagnetic fields, such as pulsed fields, alternating-current, or direct-current fields in a non-scientific manner.
History | Alternative medicine | Wikipedia | 332 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
The history of alternative medicine may refer to the history of a group of diverse medical practices that were collectively promoted as "alternative medicine" beginning in the 1970s, to the collection of individual histories of members of that group, or to the history of western medical practices that were labeled "irregular practices" by the western medical establishment. It includes the histories of complementary medicine and of integrative medicine. Before the 1970s, western practitioners that were not part of the increasingly science-based medical establishment were referred to "irregular practitioners", and were dismissed by the medical establishment as unscientific and as practicing quackery. Until the 1970s, irregular practice became increasingly marginalized as quackery and fraud, as western medicine increasingly incorporated scientific methods and discoveries, and had a corresponding increase in success of its treatments. In the 1970s, irregular practices were grouped with traditional practices of nonwestern cultures and with other unproven or disproven practices that were not part of biomedicine, with the entire group collectively marketed and promoted under the single expression "alternative medicine".
Use of alternative medicine in the west began to rise following the counterculture movement of the 1960s, as part of the rising new age movement of the 1970s. This was due to misleading mass marketing of "alternative medicine" being an effective "alternative" to biomedicine, changing social attitudes about not using chemicals and challenging the establishment and authority of any kind, sensitivity to giving equal measure to beliefs and practices of other cultures (cultural relativism), and growing frustration and desperation by patients about limitations and side effects of science-based medicine. At the same time, in 1975, the American Medical Association, which played the central role in fighting quackery in the United States, abolished its quackery committee and closed down its Department of Investigation. By the early to mid 1970s the expression "alternative medicine" came into widespread use, and the expression became mass marketed as a collection of "natural" and effective treatment "alternatives" to science-based biomedicine. By 1983, mass marketing of "alternative medicine" was so pervasive that the British Medical Journal (BMJ) pointed to "an apparently endless stream of books, articles, and radio and television programmes urge on the public the virtues of (alternative medicine) treatments ranging from meditation to drilling a hole in the skull to let in more oxygen". | Alternative medicine | Wikipedia | 483 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
An analysis of trends in the criticism of complementary and alternative medicine (CAM) in five prestigious American medical journals during the period of reorganization within medicine (1965–1999) was reported as showing that the medical profession had responded to the growth of CAM in three phases, and that in each phase, changes in the medical marketplace had influenced the type of response in the journals. Changes included relaxed medical licensing, the development of managed care, rising consumerism, and the establishment of the USA Office of Alternative Medicine (later National Center for Complementary and Alternative Medicine, currently National Center for Complementary and Integrative Health).
Medical education
Mainly as a result of reforms following the Flexner Report of 1910 medical education in established medical schools in the US has generally not included alternative medicine as a teaching topic. Typically, their teaching is based on current practice and scientific knowledge about: anatomy, physiology, histology, embryology, neuroanatomy, pathology, pharmacology, microbiology and immunology. Medical schools' teaching includes such topics as doctor-patient communication, ethics, the art of medicine, and engaging in complex clinical reasoning (medical decision-making). Writing in 2002, Snyderman and Weil remarked that by the early twentieth century the Flexner model had helped to create the 20th-century academic health center, in which education, research, and practice were inseparable. While this had much improved medical practice by defining with increasing certainty the pathophysiological basis of disease, a single-minded focus on the pathophysiological had diverted much of mainstream American medicine from clinical conditions that were not well understood in mechanistic terms, and were not effectively treated by conventional therapies.
By 2001 some form of CAM training was being offered by at least 75 out of 125 medical schools in the US. Exceptionally, the School of Medicine of the University of Maryland, Baltimore, includes a research institute for integrative medicine (a member entity of the Cochrane Collaboration). Medical schools are responsible for conferring medical degrees, but a physician typically may not legally practice medicine until licensed by the local government authority. Licensed physicians in the US who have attended one of the established medical schools there have usually graduated Doctor of Medicine (MD). All states require that applicants for MD licensure be graduates of an approved medical school and complete the United States Medical Licensing Examination (USMLE).
Efficacy | Alternative medicine | Wikipedia | 485 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
There is a general scientific consensus that alternative therapies lack the requisite scientific validation, and their effectiveness is either unproved or disproved. Many of the claims regarding the efficacy of alternative medicines are controversial, since research on them is frequently of low quality and methodologically flawed. Selective publication bias, marked differences in product quality and standardisation, and some companies making unsubstantiated claims call into question the claims of efficacy of isolated examples where there is evidence for alternative therapies.
The Scientific Review of Alternative Medicine points to confusions in the general population – a person may attribute symptomatic relief to an otherwise-ineffective therapy just because they are taking something (the placebo effect); the natural recovery from or the cyclical nature of an illness (the regression fallacy) gets misattributed to an alternative medicine being taken; a person not diagnosed with science-based medicine may never originally have had a true illness diagnosed as an alternative disease category.
Edzard Ernst, the first university professor of Complementary and Alternative Medicine, characterized the evidence for many alternative techniques as weak, nonexistent, or negative and in 2011 published his estimate that about 7.4% were based on "sound evidence", although he believes that may be an overestimate. Ernst has concluded that 95% of the alternative therapies he and his team studied, including acupuncture, herbal medicine, homeopathy, and reflexology, are "statistically indistinguishable from placebo treatments", but he also believes there is something that conventional doctors can usefully learn from the chiropractors and homeopath: this is the therapeutic value of the placebo effect, one of the strangest phenomena in medicine.
In 2003, a project funded by the CDC identified 208 condition-treatment pairs, of which 58% had been studied by at least one randomized controlled trial (RCT), and 23% had been assessed with a meta-analysis. According to a 2005 book by a US Institute of Medicine panel, the number of RCTs focused on CAM has risen dramatically. | Alternative medicine | Wikipedia | 432 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
, the Cochrane Library had 145 CAM-related Cochrane systematic reviews and 340 non-Cochrane systematic reviews. An analysis of the conclusions of only the 145 Cochrane reviews was done by two readers. In 83% of the cases, the readers agreed. In the 17% in which they disagreed, a third reader agreed with one of the initial readers to set a rating. These studies found that, for CAM, 38.4% concluded positive effect or possibly positive (12.4%), 4.8% concluded no effect, 0.7% concluded harmful effect, and 56.6% concluded insufficient evidence. An assessment of conventional treatments found that 41.3% concluded positive or possibly positive effect, 20% concluded no effect, 8.1% concluded net harmful effects, and 21.3% concluded insufficient evidence. However, the CAM review used the more developed 2004 Cochrane database, while the conventional review used the initial 1998 Cochrane database.
Alternative therapies do not "complement" (improve the effect of, or mitigate the side effects of) functional medical treatment. Significant drug interactions caused by alternative therapies may instead negatively impact functional treatment by making prescription drugs less effective, such as interference by herbal preparations with warfarin.
In the same way as for conventional therapies, drugs, and interventions, it can be difficult to test the efficacy of alternative medicine in clinical trials. In instances where an established, effective, treatment for a condition is already available, the Helsinki Declaration states that withholding such treatment is unethical in most circumstances. Use of standard-of-care treatment in addition to an alternative technique being tested may produce confounded or difficult-to-interpret results.
Cancer researcher Andrew J. Vickers has stated:
Perceived mechanism of effect
Anything classified as alternative medicine by definition does not have a proven healing or medical effect. However, there are different mechanisms through which it can be perceived to "work". The common denominator of these mechanisms is that effects are mis-attributed to the alternative treatment.
Placebo effect
A placebo is a treatment with no intended therapeutic value. An example of a placebo is an inert pill, but it can include more dramatic interventions like sham surgery. The placebo effect is the concept that patients will perceive an improvement after being treated with an inert treatment. The opposite of the placebo effect is the nocebo effect, when patients who expect a treatment to be harmful will perceive harmful effects after taking it. | Alternative medicine | Wikipedia | 498 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Placebos do not have a physical effect on diseases or improve overall outcomes, but patients may report improvements in subjective outcomes such as pain and nausea. A 1955 study suggested that a substantial part of a medicine's impact was due to the placebo effect. However, reassessments found the study to have flawed methodology. This and other modern reviews suggest that other factors like natural recovery and reporting bias should also be considered.
All of these are reasons why alternative therapies may be credited for improving a patient's condition even though the objective effect is non-existent, or even harmful. David Gorski argues that alternative treatments should be treated as a placebo, rather than as medicine. Almost none have performed significantly better than a placebo in clinical trials. Furthermore, distrust of conventional medicine may lead to patients experiencing the nocebo effect when taking effective medication.
Regression to the mean
A patient who receives an inert treatment may report improvements afterwards that it did not cause. Assuming it was the cause without evidence is an example of the regression fallacy. This may be due to a natural recovery from the illness, or a fluctuation in the symptoms of a long-term condition. The concept of regression toward the mean implies that an extreme result is more likely to be followed by a less extreme result.
Other factors
There are also reasons why a placebo treatment group may outperform a "no-treatment" group in a test which are not related to a patient's experience. These include patients reporting more favourable results than they really felt due to politeness or "experimental subordination", observer bias, and misleading wording of questions. In their 2010 systematic review of studies into placebos, Asbjørn Hróbjartsson and Peter C. Gøtzsche write that "even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding." Alternative therapies may also be credited for perceived improvement through decreased use or effect of medical treatment, and therefore either decreased side effects or nocebo effects towards standard treatment.
Use and regulation
Appeal
Practitioners of complementary medicine usually discuss and advise patients as to available alternative therapies. Patients often express interest in mind-body complementary therapies because they offer a non-drug approach to treating some health conditions. | Alternative medicine | Wikipedia | 483 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
In addition to the social-cultural underpinnings of the popularity of alternative medicine, there are several psychological issues that are critical to its growth, notably psychological effects, such as the will to believe, cognitive biases that help maintain self-esteem and promote harmonious social functioning, and the post hoc, ergo propter hoc fallacy.
In a 2018 interview with The BMJ, Edzard Ernst stated: "The present popularity of complementary and alternative medicine is also inviting criticism of what we are doing in mainstream medicine. It shows that we aren't fulfilling a certain need-we are not giving patients enough time, compassion, or empathy. These are things that complementary practitioners are very good at. Mainstream medicine could learn something from complementary medicine."
Marketing
Alternative medicine is a profitable industry with large media advertising expenditures. Accordingly, alternative practices are often portrayed positively and compared favorably to "big pharma".
The popularity of complementary & alternative medicine (CAM) may be related to other factors that Ernst mentioned in a 2008 interview in The Independent:
Paul Offit proposed that "alternative medicine becomes quackery" in four ways: by recommending against conventional therapies that are helpful, promoting potentially harmful therapies without adequate warning, draining patients' bank accounts, or by promoting "magical thinking". Promoting alternative medicine has been called dangerous and unethical.
Social factors
Authors have speculated on the socio-cultural and psychological reasons for the appeal of alternative medicines among the minority using them in lieu of conventional medicine. There are several socio-cultural reasons for the interest in these treatments centered on the low level of scientific literacy among the public at large and a concomitant increase in antiscientific attitudes and new age mysticism. Related to this are vigorous marketing of extravagant claims by the alternative medical community combined with inadequate media scrutiny and attacks on critics. Alternative medicine is criticized for taking advantage of the least fortunate members of society.
There is also an increase in conspiracy theories toward conventional medicine and pharmaceutical companies, mistrust of traditional authority figures, such as the physician, and a dislike of the current delivery methods of scientific biomedicine, all of which have led patients to seek out alternative medicine to treat a variety of ailments. Many patients lack access to contemporary medicine, due to a lack of private or public health insurance, which leads them to seek out lower-cost alternative medicine. Medical doctors are also aggressively marketing alternative medicine to profit from this market. | Alternative medicine | Wikipedia | 499 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Patients can be averse to the painful, unpleasant, and sometimes-dangerous side effects of biomedical treatments. Treatments for severe diseases such as cancer and HIV infection have well-known, significant side-effects. Even low-risk medications such as antibiotics can have potential to cause life-threatening anaphylactic reactions in a very few individuals. Many medications may cause minor but bothersome symptoms such as cough or upset stomach. In all of these cases, patients may be seeking out alternative therapies to avoid the adverse effects of conventional treatments.
Prevalence of use
According to research published in 2015, the increasing popularity of CAM needs to be explained by moral convictions or lifestyle choices rather than by economic reasoning.
In developing nations, access to essential medicines is severely restricted by lack of resources and poverty. Traditional remedies, often closely resembling or forming the basis for alternative remedies, may comprise primary healthcare or be integrated into the healthcare system. In Africa, traditional medicine is used for 80% of primary healthcare, and in developing nations as a whole over one-third of the population lack access to essential medicines.
In Latin America, inequities against BIPOC communities keep them tied to their traditional practices and therefore, it is often these communities that constitute the majority of users of alternative medicine. Racist attitudes towards certain communities disable them from accessing more urbanized modes of care. In a study that assessed access to care in rural communities of Latin America, it was found that discrimination is a huge barrier to the ability of citizens to access care; more specifically, women of Indigenous and African descent, and lower-income families were especially hurt. Such exclusion exacerbates the inequities that minorities in Latin America already face. Consistently excluded from many systems of westernized care for socioeconomic and other reasons, low-income communities of color often turn to traditional medicine for care as it has proved reliable to them across generations. | Alternative medicine | Wikipedia | 387 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Commentators including David Horrobin have proposed adopting a prize system to reward medical research. This stands in opposition to the current mechanism for funding research proposals in most countries around the world. In the US, the NCCIH provides public research funding for alternative medicine. The NCCIH has spent more than US$2.5 billion on such research since 1992 and this research has not demonstrated the efficacy of alternative therapies. As of 2011, the NCCIH's sister organization in the NIC Office of Cancer Complementary and Alternative Medicine had given out grants of around $105 million each year for several years. Testing alternative medicine that has no scientific basis (as in the aforementioned grants) has been called a waste of scarce research resources.
That alternative medicine has been on the rise "in countries where Western science and scientific method generally are accepted as the major foundations for healthcare, and 'evidence-based' practice is the dominant paradigm" was described as an "enigma" in the Medical Journal of Australia. A 15-year systematic review published in 2022 on the global acceptance and use of CAM among medical specialists found the overall acceptance of CAM at 52% and the overall use at 45%.
In the United States
In the United States, the 1974 Child Abuse Prevention and Treatment Act (CAPTA) required that for states to receive federal money, they had to grant religious exemptions to child neglect and abuse laws regarding religion-based healing practices. Thirty-one states have child-abuse religious exemptions.
The use of alternative medicine in the US has increased, with a 50 percent increase in expenditures and a 25 percent increase in the use of alternative therapies between 1990 and 1997 in America. According to a national survey conducted in 2002, "36 percent of U.S. adults aged 18 years and over use some form of complementary and alternative medicine." Americans spend many billions on the therapies annually. Most Americans used CAM to treat and/or prevent musculoskeletal conditions or other conditions associated with chronic or recurring pain. In America, women were more likely than men to use CAM, with the biggest difference in use of mind-body therapies including prayer specifically for health reasons". In 2008, more than 37% of American hospitals offered alternative therapies, up from 27 percent in 2005, and 25% in 2004. More than 70% of the hospitals offering CAM were in urban areas. | Alternative medicine | Wikipedia | 486 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
A survey of Americans found that 88 percent thought that "there are some good ways of treating sickness that medical science does not recognize". Use of magnets was the most common tool in energy medicine in America, and among users of it, 58 percent described it as at least "sort of scientific", when it is not at all scientific. In 2002, at least 60 percent of US medical schools have at least some class time spent teaching alternative therapies. "Therapeutic touch" was taught at more than 100 colleges and universities in 75 countries before the practice was debunked by a nine-year-old child for a school science project.
Prevalence of use of specific therapies
The most common CAM therapies used in the US in 2002 were prayer (45%), herbalism (19%), breathing meditation (12%), meditation (8%), chiropractic medicine (8%), yoga (5–6%), body work (5%), diet-based therapy (4%), progressive relaxation (3%), mega-vitamin therapy (3%) and visualization (2%).
In Britain, the most often used alternative therapies were Alexander technique, aromatherapy, Bach and other flower remedies, body work therapies including massage, Counseling stress therapies, hypnotherapy, meditation, reflexology, Shiatsu, Ayurvedic medicine, nutritional medicine, and yoga. Ayurvedic medicine remedies are mainly plant based with some use of animal materials. Safety concerns include the use of herbs containing toxic compounds and the lack of quality control in Ayurvedic facilities.
According to the National Health Service (England), the most commonly used complementary and alternative medicines (CAM) supported by the NHS in the UK are: acupuncture, aromatherapy, chiropractic, homeopathy, massage, osteopathy and clinical hypnotherapy. | Alternative medicine | Wikipedia | 410 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
In palliative care
Complementary therapies are often used in palliative care or by practitioners attempting to manage chronic pain in patients. Integrative medicine is considered more acceptable in the interdisciplinary approach used in palliative care than in other areas of medicine. "From its early experiences of care for the dying, palliative care took for granted the necessity of placing patient values and lifestyle habits at the core of any design and delivery of quality care at the end of life. If the patient desired complementary therapies, and as long as such treatments provided additional support and did not endanger the patient, they were considered acceptable." The non-pharmacologic interventions of complementary medicine can employ mind-body interventions designed to "reduce pain and concomitant mood disturbance and increase quality of life."
Regulation
The alternative medicine lobby has successfully pushed for alternative therapies to be subject to far less regulation than conventional medicine. Some professions of complementary/traditional/alternative medicine, such as chiropractic, have achieved full regulation in North America and other parts of the world and are regulated in a manner similar to that governing science-based medicine. In contrast, other approaches may be partially recognized and others have no regulation at all. In some cases, promotion of alternative therapies is allowed when there is demonstrably no effect, only a tradition of use. Despite laws making it illegal to market or promote alternative therapies for use in cancer treatment, many practitioners promote them.
Regulation and licensing of alternative medicine ranges widely from country to country, and state to state. In Austria and Germany complementary and alternative medicine is mainly in the hands of doctors with MDs, and half or more of the American alternative practitioners are licensed MDs. In Germany herbs are tightly regulated: half are prescribed by doctors and covered by health insurance.
Government bodies in the US and elsewhere have published information or guidance about alternative medicine. The U.S. Food and Drug Administration (FDA), has issued online warnings for consumers about medication health fraud. This includes a section on Alternative Medicine Fraud, such as a warning that Ayurvedic products generally have not been approved by the FDA before marketing.
Risks and problems
The National Science Foundation has studied the problematic side of the public's attitudes and understandings of science fiction, pseudoscience, and belief in alternative medicine. They use a quote from Robert L. Park to describe some issues with alternative medicine:
Negative outcomes | Alternative medicine | Wikipedia | 496 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
According to the Institute of Medicine, use of alternative medical techniques may result in several types of harm:
"Direct harm, which results in adverse patient outcome."
"Economic harm, which results in monetary loss but presents no health hazard;"
"Indirect harm, which results in a delay of appropriate treatment, or in unreasonable expectations that discourage patients and their families from accepting and dealing effectively with their medical conditions;"
Interactions with conventional pharmaceuticals
Forms of alternative medicine that are biologically active can be dangerous even when used in conjunction with conventional medicine. Examples include immuno-augmentation therapy, shark cartilage, bioresonance therapy, oxygen and ozone therapies, and insulin potentiation therapy. Some herbal remedies can cause dangerous interactions with chemotherapy drugs, radiation therapy, or anesthetics during surgery, among other problems. An example of these dangers was reported by Associate Professor Alastair MacLennan of Adelaide University, Australia regarding a patient who almost bled to death on the operating table after neglecting to mention that she had been taking "natural" potions to "build up her strength" before the operation, including a powerful anticoagulant that nearly caused her death.
To ABC Online, MacLennan also gives another possible mechanism:
Side-effects
Conventional treatments are subjected to testing for undesired side-effects, whereas alternative therapies, in general, are not subjected to such testing at all. Any treatment – whether conventional or alternative – that has a biological or psychological effect on a patient may also have potential to possess dangerous biological or psychological side-effects. Attempts to refute this fact with regard to alternative therapies sometimes use the appeal to nature fallacy, i.e., "That which is natural cannot be harmful." Specific groups of patients such as patients with impaired hepatic or renal function are more susceptible to side effects of alternative remedies. | Alternative medicine | Wikipedia | 387 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
An exception to the normal thinking regarding side-effects is homeopathy. Since 1938, the FDA has regulated homeopathic products in "several significantly different ways from other drugs." Homeopathic preparations, termed "remedies", are extremely dilute, often far beyond the point where a single molecule of the original active (and possibly toxic) ingredient is likely to remain. They are, thus, considered safe on that count, but "their products are exempt from good manufacturing practice requirements related to expiration dating and from finished product testing for identity and strength", and their alcohol concentration may be much higher than allowed in conventional drugs.
Treatment delay
Alternative medicine may discourage people from getting the best possible treatment. Those having experienced or perceived success with one alternative therapy for a minor ailment may be convinced of its efficacy and persuaded to extrapolate that success to some other alternative therapy for a more serious, possibly life-threatening illness. For this reason, critics argue that therapies that rely on the placebo effect to define success are very dangerous. According to mental health journalist Scott Lilienfeld in 2002, "unvalidated or scientifically unsupported mental health practices can lead individuals to forgo effective treatments" and refers to this as opportunity cost. Individuals who spend large amounts of time and money on ineffective treatments may be left with precious little of either, and may forfeit the opportunity to obtain treatments that could be more helpful. In short, even innocuous treatments can indirectly produce negative outcomes. Between 2001 and 2003, four children died in Australia because their parents chose ineffective naturopathic, homeopathic, or other alternative medicines and diets rather than conventional therapies.
Unconventional cancer "cures"
There have always been "many therapies offered outside of conventional cancer treatment centers and based on theories not found in biomedicine. These alternative cancer cures have often been described as 'unproven,' suggesting that appropriate clinical trials have not been conducted and that the therapeutic value of the treatment is unknown." However, "many alternative cancer treatments have been investigated in good-quality clinical trials, and they have been shown to be ineffective.... The label 'unproven' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been 'disproven'."
Edzard Ernst has stated:
Rejection of science | Alternative medicine | Wikipedia | 491 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Complementary and alternative medicine (CAM) is not as well researched as conventional medicine, which undergoes intense research before release to the public. Practitioners of science-based medicine also discard practices and treatments when they are shown ineffective, while alternative practitioners do not. Funding for research is also sparse making it difficult to do further research for effectiveness of CAM. Most funding for CAM is funded by government agencies. Proposed research for CAM are rejected by most private funding agencies because the results of research are not reliable. The research for CAM has to meet certain standards from research ethics committees, which most CAM researchers find almost impossible to meet. Even with the little research done on it, CAM has not been proven to be effective. Studies that have been done will be cited by CAM practitioners in an attempt to claim a basis in science. These studies tend to have a variety of problems, such as small samples, various biases, poor research design, lack of controls, negative results, etc. Even those with positive results can be better explained as resulting in false positives due to bias and noisy data.
Alternative medicine may lead to a false understanding of the body and of the process of science. Steven Novella, a neurologist at Yale School of Medicine, wrote that government-funded studies of integrating alternative medicine techniques into the mainstream are "used to lend an appearance of legitimacy to treatments that are not legitimate." Marcia Angell considered that critics felt that healthcare practices should be classified based solely on scientific evidence, and if a treatment had been rigorously tested and found safe and effective, science-based medicine will adopt it regardless of whether it was considered "alternative" to begin with. It is possible for a method to change categories (proven vs. unproven), based on increased knowledge of its effectiveness or lack thereof. Prominent supporters of this position are George D. Lundberg, former editor of the Journal of the American Medical Association (JAMA) and the journal's interim editor-in-chief Phil Fontanarosa.
Writing in 1999 in CA: A Cancer Journal for Clinicians Barrie R. Cassileth mentioned a 1997 letter to the United States Senate's Subcommittee on Public Health and Safety, which had deplored the lack of critical thinking and scientific rigor in OAM-supported research, had been signed by four Nobel Laureates and other prominent scientists. (This was supported by the National Institutes of Health (NIH).) | Alternative medicine | Wikipedia | 488 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
In March 2009, a staff writer for The Washington Post reported that the impending national discussion about broadening access to health care, improving medical practice and saving money was giving a group of scientists an opening to propose shutting down the National Center for Complementary and Alternative Medicine. They quoted one of these scientists, Steven Salzberg, a genome researcher and computational biologist at the University of Maryland, as saying "One of our concerns is that NIH is funding pseudoscience." They noted that the vast majority of studies were based on fundamental misunderstandings of physiology and disease, and had shown little or no effect.
Writers such as Carl Sagan, a noted astrophysicist, advocate of scientific skepticism and the author of The Demon-Haunted World: Science as a Candle in the Dark (1996), have lambasted the lack of empirical evidence to support the existence of the putative energy fields on which these therapies are predicated.
Sampson has also pointed out that CAM tolerated contradiction without thorough reason and experiment. Barrett has pointed out that there is a policy at the NIH of never saying something does not work, only that a different version or dose might give different results. Barrett also expressed concern that, just because some "alternatives" have merit, there is the impression that the rest deserve equal consideration and respect even though most are worthless, since they are all classified under the one heading of alternative medicine.
Some critics of alternative medicine are focused upon health fraud, misinformation, and quackery as public health problems, notably Wallace Sampson and Paul Kurtz founders of Scientific Review of Alternative Medicine and Stephen Barrett, co-founder of The National Council Against Health Fraud and webmaster of Quackwatch. Grounds for opposing alternative medicine include that:
Alternative therapies typically lack any scientific validation, and their effectiveness either is unproven or has been disproved.
It is usually based on religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, or fraud.
Methods may incorporate or base themselves on traditional medicine, folk knowledge, spiritual beliefs, ignorance or misunderstanding of scientific principles, errors in reasoning, or newly conceived approaches claiming to heal.
Research on alternative medicine is frequently of low quality and methodologically flawed.
Treatments are not part of the conventional, science-based healthcare system.
Where alternative therapies have replaced conventional science-based medicine, even with the safest alternative medicines, failure to use or delay in using conventional science-based medicine has caused deaths. | Alternative medicine | Wikipedia | 509 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Many alternative medical treatments are not patentable, which may lead to less research funding from the private sector. In addition, in most countries, alternative therapies (in contrast to pharmaceuticals) can be marketed without any proof of efficacy – also a disincentive for manufacturers to fund scientific research.
English evolutionary biologist Richard Dawkins, in his 2003 book A Devil's Chaplain, defined alternative medicine as a "set of practices that cannot be tested, refuse to be tested, or consistently fail tests." Dawkins argued that if a technique is demonstrated effective in properly performed trials then it ceases to be alternative and simply becomes medicine.
CAM is also often less regulated than conventional medicine. There are ethical concerns about whether people who perform CAM have the proper knowledge to treat patients. CAM is often done by non-physicians who do not operate with the same medical licensing laws which govern conventional medicine, and it is often described as an issue of non-maleficence.
According to two writers, Wallace Sampson and K. Butler, marketing is part of the training required in alternative medicine, and propaganda methods in alternative medicine have been traced back to those used by Hitler and Goebels in their promotion of pseudoscience in medicine.
In November 2011 Edzard Ernst stated that the "level of misinformation about alternative medicine has now reached the point where it has become dangerous and unethical. So far, alternative medicine has remained an ethics-free zone. It is time to change this."
Harriet Hall criticized the low standard of evidence accepted by the alternative medicine community: | Alternative medicine | Wikipedia | 318 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
Conflicts of interest
Some commentators have said that special consideration must be given to the issue of conflicts of interest in alternative medicine. Edzard Ernst has said that most researchers into alternative medicine are at risk of "unidirectional bias" because of a generally uncritical belief in their chosen subject. Ernst cites as evidence the phenomenon whereby 100% of a sample of acupuncture trials originating in China had positive conclusions. David Gorski contrasts evidence-based medicine, in which researchers try to disprove hyphotheses, with what he says is the frequent practice in pseudoscience-based research, of striving to confirm pre-existing notions. Harriet Hall writes that there is a contrast between the circumstances of alternative medicine practitioners and disinterested scientists: in the case of acupuncture, for example, an acupuncturist would have "a great deal to lose" if acupuncture were rejected by research; but the disinterested skeptic would not lose anything if its effects were confirmed; rather their change of mind would enhance their skeptical credentials.
Use of health and research resources
Research into alternative therapies has been criticized for "diverting research time, money, and other resources from more fruitful lines of investigation in order to pursue a theory that has no basis in biology." Research methods expert and author of Snake Oil Science, R. Barker Bausell, has stated that "it's become politically correct to investigate nonsense." A commonly cited statistic is that the US National Institute of Health had spent $2.5 billion on investigating alternative therapies prior to 2009, with none being found to be effective. | Alternative medicine | Wikipedia | 344 | 1845 | https://en.wikipedia.org/wiki/Alternative%20medicine | Biology and health sciences | Alternative and traditional medicine | null |
An allele (or allelomorph) is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.
Alleles can differ at a single position through single nucleotide polymorphisms (SNP), but they can also have insertions and deletions of up to several thousand base pairs.
Most alleles observed result in little or no change in the function of the gene product it codes for. However, sometimes different alleles can result in different observable phenotypic traits, such as different pigmentation. A notable example of this is Gregor Mendel's discovery that the white and purple flower colors in pea plants were the result of a single gene with two alleles.
Nearly all multicellular organisms have two sets of chromosomes at some point in their biological life cycle; that is, they are diploid. For a given locus, if the two chromosomes contain the same allele, they, and the organism, are homozygous with respect to that allele. If the alleles are different, they, and the organism, are heterozygous with respect to those alleles.
Popular definitions of 'allele' typically refer only to different alleles within genes. For example, the ABO blood grouping is controlled by the ABO gene, which has six common alleles (variants). In population genetics, nearly every living human's phenotype for the ABO gene is some combination of just these six alleles.
Etymology
The word "allele" is a short form of "allelomorph" ("other form", a word coined by British geneticists William Bateson and Edith Rebecca Saunders) in the 1900s, which was used in the early days of genetics to describe variant forms of a gene detected in different phenotypes and identified to cause the differences between them. It derives from the Greek prefix ἀλληλο-, allelo-, meaning "mutual", "reciprocal", or "each other", which itself is related to the Greek adjective ἄλλος, allos (cognate with Latin alius), meaning "other".
Alleles that lead to dominant or recessive phenotypes | Allele | Wikipedia | 463 | 1911 | https://en.wikipedia.org/wiki/Allele | Biology and health sciences | Genetics | Biology |
In many cases, genotypic interactions between the two alleles at a locus can be described as dominant or recessive, according to which of the two homozygous phenotypes the heterozygote most resembles. Where the heterozygote is indistinguishable from one of the homozygotes, the allele expressed is the one that leads to the "dominant" phenotype, and the other allele is said to be "recessive". The degree and pattern of dominance varies among loci. This type of interaction was first formally-described by Gregor Mendel. However, many traits defy this simple categorization and the phenotypes are modelled by co-dominance and polygenic inheritance.
The term "wild type" allele is sometimes used to describe an allele that is thought to contribute to the typical phenotypic character as seen in "wild" populations of organisms, such as fruit flies (Drosophila melanogaster). Such a "wild type" allele was historically regarded as leading to a dominant (overpowering – always expressed), common, and normal phenotype, in contrast to "mutant" alleles that lead to recessive, rare, and frequently deleterious phenotypes. It was formerly thought that most individuals were homozygous for the "wild type" allele at most gene loci, and that any alternative "mutant" allele was found in homozygous form in a small minority of "affected" individuals, often as genetic diseases, and more frequently in heterozygous form in "carriers" for the mutant allele. It is now appreciated that most or all gene loci are highly polymorphic, with multiple alleles, whose frequencies vary from population to population, and that a great deal of genetic variation is hidden in the form of alleles that do not produce obvious phenotypic differences. Wild type alleles are often denoted by a superscript plus sign (i.e., p for an allele p).
Multiple alleles | Allele | Wikipedia | 430 | 1911 | https://en.wikipedia.org/wiki/Allele | Biology and health sciences | Genetics | Biology |
A population or species of organisms typically includes multiple alleles at each locus among various individuals. Allelic variation at a locus is measurable as the number of alleles (polymorphism) present, or the proportion of heterozygotes in the population. A null allele is a gene variant that lacks the gene's normal function because it either is not expressed, or the expressed protein is inactive.
For example, at the gene locus for the ABO blood type carbohydrate antigens in humans, classical genetics recognizes three alleles, IA, IB, and i, which determine compatibility of blood transfusions. Any individual has one of six possible genotypes (IAIA, IAi, IBIB, IBi, IAIB, and ii) which produce one of four possible phenotypes: "Type A" (produced by IAIA homozygous and IAi heterozygous genotypes), "Type B" (produced by IBIB homozygous and IBi heterozygous genotypes), "Type AB" produced by IAIB heterozygous genotype, and "Type O" produced by ii homozygous genotype. (It is now known that each of the A, B, and O alleles is actually a class of multiple alleles with different DNA sequences that produce proteins with identical properties: more than 70 alleles are known at the ABO locus. Hence an individual with "Type A" blood may be an AO heterozygote, an AA homozygote, or an AA heterozygote with two different "A" alleles.)
Genotype frequencies
The frequency of alleles in a diploid population can be used to predict the frequencies of the corresponding genotypes (see Hardy–Weinberg principle). For a simple model, with two alleles;
where p is the frequency of one allele and q is the frequency of the alternative allele, which necessarily sum to unity. Then, p2 is the fraction of the population homozygous for the first allele, 2pq is the fraction of heterozygotes, and q2 is the fraction homozygous for the alternative allele. If the first allele is dominant to the second then the fraction of the population that will show the dominant phenotype is p2 + 2pq, and the fraction with the recessive phenotype is q2. | Allele | Wikipedia | 511 | 1911 | https://en.wikipedia.org/wiki/Allele | Biology and health sciences | Genetics | Biology |
With three alleles:
and
In the case of multiple alleles at a diploid locus, the number of possible genotypes (G) with a number of alleles (a) is given by the expression:
Allelic dominance in genetic disorders
A number of genetic disorders are caused when an individual inherits two recessive alleles for a single-gene trait. Recessive genetic disorders include albinism, cystic fibrosis, galactosemia, phenylketonuria (PKU), and Tay–Sachs disease. Other disorders are also due to recessive alleles, but because the gene locus is located on the X chromosome, so that males have only one copy (that is, they are hemizygous), they are more frequent in males than in females. Examples include red–green color blindness and fragile X syndrome.
Other disorders, such as Huntington's disease, occur when an individual inherits only one dominant allele.
Epialleles
While heritable traits are typically studied in terms of genetic alleles, epigenetic marks such as DNA methylation can be inherited at specific genomic regions in certain species, a process termed transgenerational epigenetic inheritance. The term epiallele is used to distinguish these heritable marks from traditional alleles, which are defined by nucleotide sequence. A specific class of epiallele, the metastable epialleles, has been discovered in mice and in humans which is characterized by stochastic (probabilistic) establishment of epigenetic state that can be mitotically inherited.
Idiomorph
The term "idiomorph", from Greek 'morphos' (form) and 'idio' (singular, unique), was introduced in 1990 in place of "allele" to denote sequences at the same locus in different strains that have no sequence similarity and probably do not share a common phylogenetic relationship. It is used mainly in the genetic research of mycology. | Allele | Wikipedia | 415 | 1911 | https://en.wikipedia.org/wiki/Allele | Biology and health sciences | Genetics | Biology |
Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.
Common side effects include rash, nausea, and diarrhea. It should not be used in people who are allergic to penicillin. Serious side effects may include Clostridioides difficile colitis or anaphylaxis. While usable in those with kidney problems, the dose may need to be decreased. Its use during pregnancy and breastfeeding appears to be generally safe.
Ampicillin was discovered in 1958 and came into commercial use in 1961. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies ampicillin as critically important for human medicine. It is available as a generic medication.
Medical uses
Diseases
Bacterial meningitis; an aminoglycoside can be added to increase efficacy against gram-negative meningitis bacteria
Endocarditis by enterococcal strains (off-label use); often given with an aminoglycoside
Gastrointestinal infections caused by contaminated water or food (for example, by Salmonella)
Genito-urinary tract infections
Healthcare-associated infections that are related to infections from using urinary catheters and that are unresponsive to other medications
Otitis media (middle ear infection)
Prophylaxis (i.e. to prevent infection) in those who previously had rheumatic heart disease or are undergoing dental procedures, vaginal hysterectomies, or C-sections. It is also used in pregnant woman who are carriers of group B streptococci to prevent early-onset neonatal infections.
Respiratory infections, including bronchitis, pharyngitis
Sinusitis
Sepsis
Whooping cough, to prevent and treat secondary infections
Ampicillin used to also be used to treat gonorrhea, but there are now too many strains resistant to penicillins. | Ampicillin | Wikipedia | 470 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Bacteria
Ampicillin is used to treat infections by many gram-positive and gram-negative bacteria. It was the first "broad spectrum" penicillin with activity against gram-positive bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, some isolates of Staphylococcus aureus (but not penicillin-resistant or methicillin-resistant strains), Trueperella, and some Enterococcus. It is one of the few antibiotics that works against multidrug resistant Enterococcus faecalis and E. faecium. Activity against gram-negative bacteria includes Neisseria meningitidis, some Haemophilus influenzae, and some of the Enterobacteriaceae (though most Enterobacteriaceae and Pseudomonas are resistant). Its spectrum of activity is enhanced by co-administration of sulbactam, a drug that inhibits beta lactamase, an enzyme produced by bacteria to inactivate ampicillin and related antibiotics. It is sometimes used in combination with other antibiotics that have different mechanisms of action, like vancomycin, linezolid, daptomycin, and tigecycline.
Available forms
Ampicillin can be administered by mouth, an intramuscular injection (shot) or by intravenous infusion. The oral form, available as capsules or oral suspensions, is not given as an initial treatment for severe infections, but rather as a follow-up to an IM or IV injection. For IV and IM injections, ampicillin is kept as a powder that must be reconstituted.
IV injections must be given slowly, as rapid IV injections can lead to convulsive seizures.
Specific populations
Ampicillin is one of the most used drugs in pregnancy, and has been found to be generally harmless both by the Food and Drug Administration in the U.S. (which classified it as category B) and the Therapeutic Goods Administration in Australia (which classified it as category A). It is the drug of choice for treating Listeria monocytogenes in pregnant women, either alone or combined with an aminoglycoside. Pregnancy increases the clearance of ampicillin by up to 50%, and a higher dose is thus needed to reach therapeutic levels. | Ampicillin | Wikipedia | 478 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Ampicillin crosses the placenta and remains in the amniotic fluid at 50–100% of the concentration in maternal plasma; this can lead to high concentrations of ampicillin in the newborn.
While lactating mothers secrete some ampicillin into their breast milk, the amount is minimal.
In newborns, ampicillin has a longer half-life and lower plasma protein binding. The clearance by the kidneys is lower, as kidney function has not fully developed.
Contraindications
Ampicillin is contraindicated in those with a hypersensitivity to penicillins, as they can cause fatal anaphylactic reactions. Hypersensitivity reactions can include frequent skin rashes and hives, exfoliative dermatitis, erythema multiforme, and a temporary decrease in both red and white blood cells.
Ampicillin is not recommended in people with concurrent mononucleosis, as over 40% of patients develop a skin rash.
Side effects
Ampicillin is comparatively less toxic than other antibiotics, and side effects are more likely in those who are sensitive to penicillins and those with a history of asthma or allergies. In very rare cases, it causes severe side effects such as angioedema, anaphylaxis, and C. difficile infection (that can range from mild diarrhea to serious pseudomembranous colitis). Some develop black "furry" tongue. Serious adverse effects also include seizures and serum sickness. The most common side effects, experienced by about 10% of users are diarrhea and rash. Less common side effects can be nausea, vomiting, itching, and blood dyscrasias. The gastrointestinal effects, such as hairy tongue, nausea, vomiting, diarrhea, and colitis, are more common with the oral form of penicillin. Other conditions may develop up several weeks after treatment.
Overdose
Ampicillin overdose can cause behavioral changes, confusion, blackouts, and convulsions, as well as neuromuscular hypersensitivity, electrolyte imbalance, and kidney failure.
Interactions | Ampicillin | Wikipedia | 440 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Ampicillin reacts with probenecid and methotrexate to decrease renal excretion. Large doses of ampicillin can increase the risk of bleeding with concurrent use of warfarin and other oral anticoagulants, possibly by inhibiting platelet aggregation. Ampicillin has been said to make oral contraceptives less effective, but this has been disputed. It can be made less effective by other antibiotic, such as chloramphenicol, erythromycin, cephalosporins, and tetracyclines. For example, tetracyclines inhibit protein synthesis in bacteria, reducing the target against which ampicillin acts. If given at the same time as aminoglycosides, it can bind to it and inactivate it. When administered separately, aminoglycosides and ampicillin can potentiate each other instead.
Ampicillin causes skin rashes more often when given with allopurinol.
Both the live cholera vaccine and live typhoid vaccine can be made ineffective if given with ampicillin. Ampicillin is normally used to treat cholera and typhoid fever, lowering the immunological response that the body has to mount.
Pharmacology
Mechanism of action
Ampicillin is in the penicillin group of beta-lactam antibiotics and is part of the aminopenicillin family. It is roughly equivalent to amoxicillin in terms of activity. Ampicillin is able to penetrate gram-positive and some gram-negative bacteria. It differs from penicillin G, or benzylpenicillin, only by the presence of an amino group. This amino group, present on both ampicillin and amoxicillin, helps these antibiotics pass through the pores of the outer membrane of gram-negative bacteria, such as Escherichia coli, Proteus mirabilis, Salmonella enterica, and Shigella.
Ampicillin acts as an irreversible inhibitor of the enzyme transpeptidase, which is needed by bacteria to make the cell wall. It inhibits the third and final stage of bacterial cell wall synthesis in binary fission, which ultimately leads to cell lysis; therefore, ampicillin is usually bacteriolytic. | Ampicillin | Wikipedia | 467 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Pharmacokinetics
Ampicillin is well-absorbed from the GI tract (though food reduces its absorption), and reaches peak concentrations in one to two hours. The bioavailability is around 62% for parenteral routes. Unlike other penicillins, which usually bind 60–90% to plasma proteins, ampicillin binds to only 15–20%.
Ampicillin is distributed through most tissues, though it is concentrated in the liver and kidneys. It can also be found in the cerebrospinal fluid when the meninges become inflamed (such as, for example, meningitis). Some ampicillin is metabolized by hydrolyzing the beta-lactam ring to penicilloic acid, though most of it is excreted unchanged. In the kidneys, it is filtered out mostly by tubular secretion; some also undergoes glomerular filtration, and the rest is excreted in the feces and bile.
Hetacillin and pivampicillin are ampicillin esters that have been developed to increase bioavailability.
History
Ampicillin has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against gram-positive organisms such as staphylococci and streptococci. Ampicillin (originally branded as "Penbritin") also demonstrated activity against gram-negative organisms such as H. influenzae, coliforms, and Proteus spp.
Society and culture
Economics
Ampicillin is relatively inexpensive. In the United States, it is available as a generic medication. | Ampicillin | Wikipedia | 353 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Veterinary use
In veterinary medicine, ampicillin is used in cats, dogs, and farm animals to treat:
Anal gland infections
Cutaneous infections, such as abscesses, cellulitis, and pustular dermatitis
E. coli and Salmonella infections in cattle, sheep, and goats (oral form). Ampicillin use for this purpose had declined as bacterial resistance has increased.
Mastitis in sows
Mixed aerobic–anaerobic infections, such as from cat bites
Multidrug-resistant Enterococcus faecalis and E. faecium
Prophylactic use in poultry against Salmonella and sepsis from E. coli or Staphylococcus aureus
Respiratory tract infections, including tonsilitis, bovine respiratory disease, shipping fever, bronchopneumonia, and calf and bovine pneumonia
Urinary tract infections in dogs
Horses are generally not treated with oral ampicillin, as they have low bioavailability of beta-lactams.
The half-life in animals is around that same of that in humans (just over an hour). Oral absorption is less than 50% in cats and dogs, and less than 4% in horses. | Ampicillin | Wikipedia | 244 | 1912 | https://en.wikipedia.org/wiki/Ampicillin | Biology and health sciences | Antibiotics | Health |
Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resistance), viruses (antiviral resistance), protozoa (antiprotozoal resistance), and fungi (antifungal resistance). Together, these adaptations fall under the AMR umbrella, posing significant challenges to healthcare worldwide. Misuse and improper management of antimicrobials are primary drivers of this resistance, though it can also occur naturally through genetic mutations and the spread of resistant genes.
Microbes resistant to multiple drugs are termed multidrug-resistant (MDR) and are sometimes called superbugs. Antibiotic resistance, a significant AMR subset, enables bacteria to survive antibiotic treatment, complicating infection management and treatment options. Resistance arises through spontaneous mutation, horizontal gene transfer, and increased selective pressure from antibiotic overuse, both in medicine and agriculture, which accelerates resistance development.
The burden of AMR is immense, with nearly 5 million annual deaths associated with resistant infections. Infections from AMR microbes are more challenging to treat and often require costly alternative therapies that may have more severe side effects. Preventive measures, such as using narrow-spectrum antibiotics and improving hygiene practices, aim to reduce the spread of resistance.
The WHO claims that AMR is one of the top global public health and development threats, estimating that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. Moreover, the WHO and other international bodies warn that AMR could lead to up to 10 million deaths annually by 2050 unless actions are taken. Global initiatives, such as calls for international AMR treaties, emphasize coordinated efforts to limit misuse, fund research, and provide access to necessary antimicrobials in developing nations. However, the COVID-19 pandemic redirected resources and scientific attention away from AMR, intensifying the challenge.
Definition | Antimicrobial resistance | Wikipedia | 429 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
The WHO defines antimicrobial resistance as a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism. A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe. All types of microbes can develop drug resistance. Thus, there are antibiotic, antifungal, antiviral and antiparasitic resistance.
Antibiotic resistance is a subset of antimicrobial resistance. This more specific resistance is linked to bacteria and thus broken down into two further subsets, microbiological and clinical. Microbiological resistance is the most common and occurs from genes, mutated or inherited, that allow the bacteria to resist the mechanism to kill the microbe associated with certain antibiotics. Clinical resistance is shown through the failure of many therapeutic techniques where the bacteria that are normally susceptible to a treatment become resistant after surviving the outcome of the treatment. In both cases of acquired resistance, the bacteria can pass the genetic catalyst for resistance through horizontal gene transfer: conjugation, transduction, or transformation. This allows the resistance to spread across the same species of pathogen or even similar bacterial pathogens.
Overview
WHO report released April 2014 stated, "this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health."
Each year, nearly 5 million deaths are associated with AMR globally. In 2019, global deaths attributable to AMR numbered 1.27 million in 2019. That same year, AMR may have contributed to 5 million deaths and one in five people who died due to AMR were children under five years old.
In 2018, WHO considered antibiotic resistance to be one of the biggest threats to global health, food security and development. Deaths attributable to AMR vary by area:
The European Centre for Disease Prevention and Control calculated that in 2015 there were 671,689 infections in the EU and European Economic Area caused by antibiotic-resistant bacteria, resulting in 33,110 deaths. Most were acquired in healthcare settings. In 2019 there were 133,000 deaths caused by AMR. | Antimicrobial resistance | Wikipedia | 496 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Causes
AMR is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. This leads to microbes either evolving a defense against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication. While antimicrobial resistance does occur naturally over time, the use of antimicrobial agents in a variety of settings both within the healthcare industry and outside of has led to antimicrobial resistance becoming increasingly more prevalent.
Although many microbes develop resistance to antibiotics over time though natural mutation, overprescribing and inappropriate prescription of antibiotics have accelerated the problem. It is possible that as many as 1 in 3 prescriptions written for antibiotics are unnecessary. Every year, approximately 154 million prescriptions for antibiotics are written. Of these, up to 46 million are unnecessary or inappropriate for the condition that the patient has. Microbes may naturally develop resistance through genetic mutations that occur during cell division, and although random mutations are rare, many microbes reproduce frequently and rapidly, increasing the chances of members of the population acquiring a mutation that increases resistance. Many individuals stop taking antibiotics when they begin to feel better. When this occurs, it is possible that the microbes that are less susceptible to treatment still remain in the body. If these microbes are able to continue to reproduce, this can lead to an infection by bacteria that are less susceptible or even resistant to an antibiotic.
Natural occurrence
AMR is a naturally occurring process. Antimicrobial resistance can evolve naturally due to continued exposure to antimicrobials. Natural selection means that organisms that are able to adapt to their environment, survive, and continue to produce offspring. As a result, the types of microorganisms that are able to survive over time with continued attack by certain antimicrobial agents will naturally become more prevalent in the environment, and those without this resistance will become obsolete. | Antimicrobial resistance | Wikipedia | 424 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Some contemporary antimicrobial resistances have also evolved naturally before the use of antimicrobials of human clinical uses. For instance, methicillin-resistance evolved as a pathogen of hedgehogs, possibly as a co-evolutionary adaptation of the pathogen to hedgehogs that are infected by a dermatophyte that naturally produces antibiotics. Also, many soil fungi and bacteria are natural competitors and the original antibiotic penicillin discovered by Alexander Fleming rapidly lost clinical effectiveness in treating humans and, furthermore, none of the other natural penicillins (F, K, N, X, O, U1 or U6) are currently in clinical use.
Antimicrobial resistance can be acquired from other microbes through swapping genes in a process termed horizontal gene transfer. This means that once a gene for resistance to an antibiotic appears in a microbial community, it can then spread to other microbes in the community, potentially moving from a non-disease causing microbe to a disease-causing microbe. This process is heavily driven by the natural selection processes that happen during antibiotic use or misuse.
Over time, most of the strains of bacteria and infections present will be the type resistant to the antimicrobial agent being used to treat them, making this agent now ineffective to defeat most microbes. With the increased use of antimicrobial agents, there is a speeding up of this natural process.
Self-medication
In the vast majority of countries, antibiotics can only be prescribed by a doctor and supplied by a pharmacy. Self-medication by consumers is defined as "the taking of medicines on one's own initiative or on another person's suggestion, who is not a certified medical professional", and it has been identified as one of the primary reasons for the evolution of antimicrobial resistance. Self-medication with antibiotics is an unsuitable way of using them but a common practice in resource-constrained countries. The practice exposes individuals to the risk of bacteria that have developed antimicrobial resistance. Many people resort to this out of necessity, when access to a physician is unavailable, or when patients have a limited amount of time or money to see a doctor. This increased access makes it extremely easy to obtain antimicrobials. An example is India, where in the state of Punjab 73% of the population resorted to treating their minor health issues and chronic illnesses through self-medication. | Antimicrobial resistance | Wikipedia | 494 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Self-medication is higher outside the hospital environment, and this is linked to higher use of antibiotics, with the majority of antibiotics being used in the community rather than hospitals. The prevalence of self-medication in low- and middle-income countries (LMICs) ranges from 8.1% to 93%. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence self-medication in low- and middle-income countries. Two significant issues with self-medication are the lack of knowledge of the public on, firstly, the dangerous effects of certain antimicrobials (for example ciprofloxacin which can cause tendonitis, tendon rupture and aortic dissection) and, secondly, broad microbial resistance and when to seek medical care if the infection is not clearing. In order to determine the public's knowledge and preconceived notions on antibiotic resistance, a screening of 3,537 articles published in Europe, Asia, and North America was done. Of the 55,225 total people surveyed in the articles, 70% had heard of antibiotic resistance previously, but 88% of those people thought it referred to some type of physical change in the human body.
Clinical misuse
Clinical misuse by healthcare professionals is another contributor to increased antimicrobial resistance. Studies done in the US show that the indication for treatment of antibiotics, choice of the agent used, and the duration of therapy was incorrect in up to 50% of the cases studied. In 2010 and 2011 about a third of antibiotic prescriptions in outpatient settings in the United States were not necessary. Another study in an intensive care unit in a major hospital in France has shown that 30% to 60% of prescribed antibiotics were unnecessary. These inappropriate uses of antimicrobial agents promote the evolution of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance. | Antimicrobial resistance | Wikipedia | 399 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
According to research conducted in the US that aimed to evaluate physicians' attitudes and knowledge on antimicrobial resistance in ambulatory settings, only 63% of those surveyed reported antibiotic resistance as a problem in their local practices, while 23% reported the aggressive prescription of antibiotics as necessary to avoid failing to provide adequate care. This demonstrates how a majority of doctors underestimate the impact that their own prescribing habits have on antimicrobial resistance as a whole. It also confirms that some physicians may be overly cautious and prescribe antibiotics for both medical or legal reasons, even when clinical indications for use of these medications are not always confirmed. This can lead to unnecessary antimicrobial use, a pattern which may have worsened during the COVID-19 pandemic.
Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.
Important to the conversation of antibiotic use is the veterinary medical system. Veterinary oversight is required by law for all medically important antibiotics. Veterinarians use the Pharmacokinetic/pharmacodynamic model (PK/PD) approach to ensuring that the correct dose of the drug is delivered to the correct place at the correct timing.
Pandemics, disinfectants and healthcare systems
Increased antibiotic use during the early waves of the COVID-19 pandemic may exacerbate this global health challenge. Moreover, pandemic burdens on some healthcare systems may contribute to antibiotic-resistant infections. On the other hand, "increased hand hygiene, decreased international travel, and decreased elective hospital procedures may have reduced AMR pathogen selection and spread in the short term" during the COVID-19 pandemic. The use of disinfectants such as alcohol-based hand sanitizers, and antiseptic hand wash may also have the potential to increase antimicrobial resistance. Extensive use of disinfectants can lead to mutations that induce antimicrobial resistance. | Antimicrobial resistance | Wikipedia | 414 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
A 2024 United Nations High-Level Meeting on AMR has pledged to reduce deaths associated with bacterial AMR by 10% over the next six years. In their first major declaration on the issue since 2016, global leaders also committed to raising $100 million to update and implement AMR action plans. However, the final draft of the declaration omitted an earlier target to reduce antibiotic use in animals by 30% by 2030, due to opposition from meat-producing countries and the farming industry. Critics argue this omission is a major weakness, as livestock accounts for around 73% of global sales of antimicrobial agents, including antibiotics, antivirals, and antiparasitics.
Environmental pollution
Considering the complex interactions between humans, animals and the environment, it is also important to consider the environmental aspects and contributors to antimicrobial resistance. Although there are still some knowledge gaps in understanding the mechanisms and transmission pathways, environmental pollution is considered a significant contributor to antimicrobial resistance. Important contributing factors are through "antibiotic residues", "industrial effluents", " agricultural runoffs", "heavy metals", "biocides and pesticides" and "sewage and wastewater" that create reservoirs for resistant genes and bacteria that facilitates the transfer of human pathogens. Unused or expired antibiotics, if not disposed of properly, can enter water systems and soil. Discharge from pharmaceutical manufacturing and other industrial companies can also introduce antibiotics and other chemicals into the environment. These factors allow for creating selective pressure for resistant bacteria. Antibiotics used in livestock and aquaculture can contaminate soil and water, which promotes resistance in environmental microbes. Heavy metals such as zinc, copper and mercury, and also biocides and pesticides, can co- select for antibiotic resistance, enhancing their speed. Inadequate treatment of sewage and wastewater allows resistant bacteria and genes to spread through water systems.
Food production
Livestock
The antimicrobial resistance crisis also extends to the food industry, specifically with food producing animals. With an ever-increasing human population, there is constant pressure to intensify productivity in many agricultural sectors, including the production of meat as a source of protein. Antibiotics are fed to livestock to act as growth supplements, and a preventive measure to decrease the likelihood of infections. | Antimicrobial resistance | Wikipedia | 461 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Farmers typically use antibiotics in animal feed to improve growth rates and prevent infections. However, this is illogical as antibiotics are used to treat infections and not prevent infections. 80% of antibiotic use in the U.S. is for agricultural purposes and about 70% of these are medically important. Overusing antibiotics gives the bacteria time to adapt leaving higher doses or even stronger antibiotics needed to combat the infection. Though antibiotics for growth promotion were banned throughout the EU in 2006, 40 countries worldwide still use antibiotics to promote growth.
This can result in the transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease. While the practice of using antibiotics as growth promoters does result in better yields and meat products, it is a major issue and needs to be decreased in order to prevent antimicrobial resistance. Though the evidence linking antimicrobial usage in livestock to antimicrobial resistance is limited, the World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance strongly recommended the reduction of use of medically important antimicrobials in livestock. Additionally, the Advisory Group stated that such antimicrobials should be expressly prohibited for both growth promotion and disease prevention in food producing animals.
By mapping antimicrobial consumption in livestock globally, it was predicted that in 228 countries there would be a total 67% increase in consumption of antibiotics by livestock by 2030. In some countries such as Brazil, Russia, India, China, and South Africa it is predicted that a 99% increase will occur. Several countries have restricted the use of antibiotics in livestock, including Canada, China, Japan, and the US. These restrictions are sometimes associated with a reduction of the prevalence of antimicrobial resistance in humans.
In the United States the Veterinary Feed Directive went into practice in 2017 dictating that All medically important antibiotics to be used in feed or water for food animal species require a veterinary feed directive (VFD) or a prescription.
Pesticides | Antimicrobial resistance | Wikipedia | 404 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Most pesticides protect crops against insects and plants, but in some cases antimicrobial pesticides are used to protect against various microorganisms such as bacteria, viruses, fungi, algae, and protozoa. The overuse of many pesticides in an effort to have a higher yield of crops has resulted in many of these microbes evolving a tolerance against these antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the US Environmental Protection Agency (EPA) and sold to market, showing the widespread use of these agents. It is estimated that for every single meal a person consumes, 0.3 g of pesticides is used, as 90% of all pesticide use is in agriculture. A majority of these products are used to help defend against the spread of infectious diseases, and hopefully protect public health. But out of the large amount of pesticides used, it is also estimated that less than 0.1% of those antimicrobial agents, actually reach their targets. That leaves over 99% of all pesticides used available to contaminate other resources. In soil, air, and water these antimicrobial agents are able to spread, coming in contact with more microorganisms and leading to these microbes evolving mechanisms to tolerate and further resist pesticides. The use of antifungal azole pesticides that drive environmental azole resistance have been linked to azole resistance cases in the clinical setting. The same issues confront the novel antifungal classes (e.g. orotomides) which are again being used in both the clinic and agriculture.
Wild birds
Wildlife, including wild and migratory birds, serve as a reservoir for zoonotic disease and antimicrobial-resistant organisms. Birds are a key link between the transmission of zoonotic diseases to human populations. By the same token, increased contact between wild birds and human populations (including domesticated animals), has increased the amount of anti-microbial resistance (AMR) to the bird population. The introduction of AMR to wild birds positively correlates with human pollution and increased human contact. Additionally, wild birds can participate in horizontal gene transfer with bacteria, leading to the transmission of antibiotic-resistant genes (ARG). | Antimicrobial resistance | Wikipedia | 463 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
For simplicity, wild bird populations can be divided into two major categories, wild sedentary birds and wild migrating birds. Wild sedentary bird exposure to AMR is through increased contact with densely populated areas, human waste, domestic animals, and domestic animal/livestock waste. Wild migrating birds interact with sedentary birds in different environments along their migration route. This increases the rate and diversity of AMR across varying ecosystems.
Neglect of wildlife in the global discussions surrounding health security and AMR, creates large barriers to true AMR surveillance. The surveillance of anti-microbial resistant organisms in wild birds is a potential metric for the rate of AMR in the environment. This surveillance also allows for further investigation into the transmission routs between different ecosystems and human populations (including domesticated animals and livestock). Such information gathered from wild bird biomes, can help identify patterns of diseased transmission and better target interventions. These targeted interventions can inform the use of antimicrobial agents and reduce the persistence of multi-drug resistant organisms.
Gene transfer from ancient microorganisms
Permafrost is a term used to refer to any ground that remained frozen for two years or more, with the oldest known examples continuously frozen for around 700,000 years. In the recent decades, permafrost has been rapidly thawing due to climate change. The cold preserves any organic matter inside the permafrost, and it is possible for microorganisms to resume their life functions once it thaws. While some common pathogens such as influenza, smallpox or the bacteria associated with pneumonia have failed to survive intentional attempts to revive them, more cold-adapted microorganisms such as anthrax, or several ancient plant and amoeba viruses, have successfully survived prolonged thaw. | Antimicrobial resistance | Wikipedia | 359 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Some scientists have argued that the inability of known causative agents of contagious diseases to survive being frozen and thawed makes this threat unlikely. Instead, there have been suggestions that when modern pathogenic bacteria interact with the ancient ones, they may, through horizontal gene transfer, pick up genetic sequences which are associated with antimicrobial resistance, exacerbating an already difficult issue. Antibiotics to which permafrost bacteria have displayed at least some resistance include chloramphenicol, streptomycin, kanamycin, gentamicin, tetracycline, spectinomycin and neomycin. However, other studies show that resistance levels in ancient bacteria to modern antibiotics remain lower than in the contemporary bacteria from the active layer of thawed ground above them, which may mean that this risk is "no greater" than from any other soil.
Prevention
There have been increasing public calls for global collective action to address the threat, including a proposal for an international treaty on antimicrobial resistance. Further detail and attention is still needed in order to recognize and measure trends in resistance on the international level; the idea of a global tracking system has been suggested but implementation has yet to occur. A system of this nature would provide insight to areas of high resistance as well as information necessary for evaluating programs, introducing interventions and other changes made to fight or reverse antibiotic resistance.
Duration of antimicrobials
Delaying or minimizing the use of antibiotics for certain conditions may help safely reduce their use. Antimicrobial treatment duration should be based on the infection and other health problems a person may have. For many infections once a person has improved there is little evidence that stopping treatment causes more resistance. Some, therefore, feel that stopping early may be reasonable in some cases. Other infections, however, do require long courses regardless of whether a person feels better.
Delaying antibiotics for ailments such as a sore throat and otitis media may have no difference in the rate of complications compared with immediate antibiotics, for example. When treating respiratory tract infections, clinical judgement is required as to the appropriate treatment (delayed or immediate antibiotic use). | Antimicrobial resistance | Wikipedia | 438 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
The study, "Shorter and Longer Antibiotic Durations for Respiratory Infections: To Fight Antimicrobial Resistance—A Retrospective Cross-Sectional Study in a Secondary Care Setting in the UK," highlights the urgency of reevaluating antibiotic treatment durations amidst the global challenge of antimicrobial resistance (AMR). It investigates the effectiveness of shorter versus longer antibiotic regimens for respiratory tract infections (RTIs) in a UK secondary care setting, emphasizing the need for evidence-based prescribing practices to optimize patient outcomes and combat AMR.
Monitoring and mapping
There are multiple national and international monitoring programs for drug-resistant threats, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), extended spectrum beta-lactamase (ESBL) producing Enterobacterales, vancomycin-resistant Enterococcus (VRE), and multidrug-resistant Acinetobacter baumannii (MRAB).
ResistanceOpen is an online global map of antimicrobial resistance developed by HealthMap which displays aggregated data on antimicrobial resistance from publicly available and user submitted data. The website can display data for a radius from a location. Users may submit data from antibiograms for individual hospitals or laboratories. European data is from the EARS-Net (European Antimicrobial Resistance Surveillance Network), part of the ECDC. ResistanceMap is a website by the Center for Disease Dynamics, Economics & Policy and provides data on antimicrobial resistance on a global level.
The WHO's AMR global action plan also recommends antimicrobial resistance surveillance in animals. Initial steps in the EU for establishing the veterinary counterpart EARS-Vet (EARS-Net for veterinary medicine) have been made. AMR data from pets in particular is scarce, but needed to support antibiotic stewardship in veterinary medicine.
By comparison there is a lack of national and international monitoring programs for antifungal resistance.
Limiting antimicrobial use in humans
Antimicrobial stewardship programmes appear useful in reducing rates of antimicrobial resistance. The antimicrobial stewardship program will also provide pharmacists with the knowledge to educate patients that antibiotics will not work for a virus for example. | Antimicrobial resistance | Wikipedia | 484 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Excessive antimicrobial use has become one of the top contributors to the evolution of antimicrobial resistance. Since the beginning of the antimicrobial era, antimicrobials have been used to treat a wide range of infectious diseases. Overuse of antimicrobials has become the primary cause of rising levels of antimicrobial resistance. The main problem is that doctors are willing to prescribe antimicrobials to ill-informed individuals who believe that antimicrobials can cure nearly all illnesses, including viral infections like the common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both usually viral in origin) were given prescriptions for antibiotics. These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria. Using antimicrobials without prescription is another driving force leading to the overuse of antibiotics to self-treat diseases like the common cold, cough, fever, and dysentery resulting in an epidemic of antibiotic resistance in countries like Bangladesh, risking its spread around the globe. Introducing strict antibiotic stewardship in the outpatient setting to reduce inappropriate prescribing of antibiotics may reduce the emerging bacterial resistance.
The WHO AWaRe (Access, Watch, Reserve) guidance and antibiotic book has been introduced to guide antibiotic choice for the 30 most common infections in adults and children to reduce inappropriate prescribing in primary care and hospitals. Narrow-spectrum antibiotics are preferred due to their lower resistance potential, and broad-spectrum antibiotics are only recommended for people with more severe symptoms. Some antibiotics are more likely to confer resistance, so are kept as reserve antibiotics in the AWaRe book.
Various diagnostic strategies have been employed to prevent the overuse of antifungal therapy in the clinic, proving a safe alternative to empirical antifungal therapy, and thus underpinning antifungal stewardship schemes. | Antimicrobial resistance | Wikipedia | 396 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
At the hospital level
Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials. The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing the development of resistance. Stewardship interventions may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death. Dispensing, to discharged in-house patients, the exact number of antibiotic pharmaceutical units necessary to complete an ongoing treatment can reduce antibiotic leftovers within the community as community pharmacies can have antibiotic package inefficiencies.
At the primary care level
Given the volume of care provided in primary care (general practice), recent strategies have focused on reducing unnecessary antimicrobial prescribing in this setting. Simple interventions, such as written information explaining when taking antibiotics is not necessary, for example in common infections of the upper respiratory tract, have been shown to reduce antibiotic prescribing. Various tools are also available to help professionals decide if prescribing antimicrobials is necessary.
Parental expectations, driven by the worry for their children's health, can influence how often children are prescribed antibiotics. Parents often rely on their clinician for advice and reassurance. However a lack of plain language information and not having adequate time for consultation negatively impacts this relationship. In effect parents often rely on past experiences in their expectations rather than reassurance from the clinician. Adequate time for consultation and plain language information can help parents make informed decisions and avoid unnecessary antibiotic use. | Antimicrobial resistance | Wikipedia | 334 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Parents play a critical role in reducing unnecessary antibiotic use, particularly during cold and flu season when children frequently experience respiratory illnesses. Many of these illnesses are caused by viruses, such as colds or the flu, which antibiotics cannot treat. Misusing antibiotics in these situations not only fails to benefit the child but also contributes to the emergence of antibiotic-resistant bacteria, posing a broader public health threat. To address parental concerns and reduce inappropriate prescribing, healthcare providers can offer plain-language explanations about the difference between bacterial and viral infections, alongside clear guidance on managing viral illnesses without antibiotics. Vaccinations also play a vital role in reducing the incidence of serious bacterial infections that may require antibiotic treatment, thereby helping to preserve the effectiveness of existing antibiotics. Schools further amplify the spread of infections due to close contact and shared surfaces, underscoring the importance of hygiene practices like regular handwashing, covering coughs, and staying home when unwell. These preventive measures not only reduce the need for antibiotics but also lower the overall risk of resistant bacteria spreading within communities.
The prescriber should closely adhere to the five rights of drug administration: the right patient, the right drug, the right dose, the right route, and the right time. Microbiological samples should be taken for culture and sensitivity testing before treatment when indicated and treatment potentially changed based on the susceptibility report.
Health workers and pharmacists can help tackle antibiotic resistance by: enhancing infection prevention and control; only prescribing and dispensing antibiotics when they are truly needed; prescribing and dispensing the right antibiotic(s) to treat the illness. A unit dose system implemented in community pharmacies can also reduce antibiotic leftovers at households.
At the individual level
People can help tackle resistance by using antibiotics only when infected with a bacterial infection and prescribed by a doctor; completing the full prescription even if the user is feeling better, never sharing antibiotics with others, or using leftover prescriptions. Taking antibiotics when not needed won't help the user, but instead give bacteria the option to adapt and leave the user with the side effects that come with the certain type of antibiotic. The CDC recommends that you follow these behaviors so that you avoid these negative side effects and keep the community safe from spreading drug-resistant bacteria. Practicing basic bacterial infection prevention courses, such as hygiene, also helps to prevent the spread of antibiotic-resistant bacteria. | Antimicrobial resistance | Wikipedia | 503 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Country examples
The Netherlands has the lowest rate of antibiotic prescribing in the OECD, at a rate of 11.4 defined daily doses (DDD) per 1,000 people per day in 2011. The defined daily dose (DDD) is a statistical measure of drug consumption, defined by the World Health Organization (WHO).
Germany and Sweden also have lower prescribing rates, with Sweden's rate having been declining since 2007.
Greece, France and Belgium have high prescribing rates for antibiotics of more than 28 DDD.
Water, sanitation, hygiene
Infectious disease control through improved water, sanitation and hygiene (WASH) infrastructure needs to be included in the antimicrobial resistance (AMR) agenda. The "Interagency Coordination Group on Antimicrobial Resistance" stated in 2018 that "the spread of pathogens through unsafe water results in a high burden of gastrointestinal disease, increasing even further the need for antibiotic treatment." This is particularly a problem in developing countries where the spread of infectious diseases caused by inadequate WASH standards is a major driver of antibiotic demand. Growing usage of antibiotics together with persistent infectious disease levels have led to a dangerous cycle in which reliance on antimicrobials increases while the efficacy of drugs diminishes. The proper use of infrastructure for water, sanitation and hygiene (WASH) can result in a 47–72 percent decrease of diarrhea cases treated with antibiotics depending on the type of intervention and its effectiveness. A reduction of the diarrhea disease burden through improved infrastructure would result in large decreases in the number of diarrhea cases treated with antibiotics. This was estimated as ranging from 5 million in Brazil to up to 590 million in India by the year 2030. The strong link between increased consumption and resistance indicates that this will directly mitigate the accelerating spread of AMR. Sanitation and water for all by 2030 is Goal Number 6 of the Sustainable Development Goals.
An increase in hand washing compliance by hospital staff results in decreased rates of resistant organisms.
Water supply and sanitation infrastructure in health facilities offer significant co-benefits for combatting AMR, and investment should be increased. There is much room for improvement: WHO and UNICEF estimated in 2015 that globally 38% of health facilities did not have a source of water, nearly 19% had no toilets and 35% had no water and soap or alcohol-based hand rub for handwashing. | Antimicrobial resistance | Wikipedia | 493 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Industrial wastewater treatment
Manufacturers of antimicrobials need to improve the treatment of their wastewater (by using industrial wastewater treatment processes) to reduce the release of residues into the environment.
Limiting antimicrobial use in animals and farming
It is established that the use of antibiotics in animal husbandry can give rise to AMR resistances in bacteria found in food animals to the antibiotics being administered (through injections or medicated feeds). For this reason only antimicrobials that are deemed "not-clinically relevant" are used in these practices.
Unlike resistance to antibacterials, antifungal resistance can be driven by arable farming, currently there is no regulation on the use of similar antifungal classes in agriculture and the clinic.
Recent studies have shown that the prophylactic use of "non-priority" or "non-clinically relevant" antimicrobials in feeds can potentially, under certain conditions, lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics. The possibility for co-selection of AMR resistances in the food chain pipeline may have far-reaching implications for human health.
Country examples
Europe
In 1997, European Union health ministers voted to ban avoparcin and four additional antibiotics used to promote animal growth in 1999. In 2006 a ban on the use of antibiotics in European feed, with the exception of two antibiotics in poultry feeds, became effective. In Scandinavia, there is evidence that the ban has led to a lower prevalence of antibiotic resistance in (nonhazardous) animal bacterial populations. As of 2004, several European countries established a decline of antimicrobial resistance in humans through limiting the use of antimicrobials in agriculture and food industries without jeopardizing animal health or economic cost.
United States | Antimicrobial resistance | Wikipedia | 367 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
The United States Department of Agriculture (USDA) and the Food and Drug Administration (FDA) collect data on antibiotic use in humans and in a more limited fashion in animals. About 80% of antibiotic use in the U.S. is for agriculture purposes, and about 70% of these are medically important. This gives reason for concern about the antibiotic resistance crisis in the U.S. and more reason to monitor it. The FDA first determined in 1977 that there is evidence of emergence of antibiotic-resistant bacterial strains in livestock. The long-established practice of permitting OTC sales of antibiotics (including penicillin and other drugs) to lay animal owners for administration to their own animals nonetheless continued in all states.
In 2000, the FDA announced their intention to revoke approval of fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone-resistant Campylobacter infections in humans. Legal challenges from the food animal and pharmaceutical industries delayed the final decision to do so until 2006. Fluroquinolones have been banned from extra-label use in food animals in the USA since 2007. However, they remain widely used in companion and exotic animals.
Global action plans and awareness | Antimicrobial resistance | Wikipedia | 254 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
At the 79th United Nations General Assembly High-Level Meeting on AMR on 26 September 2024, world leaders approved a political declaration committing to a clear set of targets and actions, including reducing the estimated 4.95 million human deaths associated with bacterial AMR annually by 10% by 2030.
The increasing interconnectedness of the world and the fact that new classes of antibiotics have not been developed and approved for more than 25 years highlight the extent to which antimicrobial resistance is a global health challenge. A global action plan to tackle the growing problem of resistance to antibiotics and other antimicrobial medicines was endorsed at the Sixty-eighth World Health Assembly in May 2015. One of the key objectives of the plan is to improve awareness and understanding of antimicrobial resistance through effective communication, education and training. This global action plan developed by the World Health Organization was created to combat the issue of antimicrobial resistance and was guided by the advice of countries and key stakeholders. The WHO's global action plan is composed of five key objectives that can be targeted through different means, and represents countries coming together to solve a major problem that can have future health consequences. These objectives are as follows:
improve awareness and understanding of antimicrobial resistance through effective communication, education and training.
strengthen the knowledge and evidence base through surveillance and research.
reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures.
optimize the use of antimicrobial medicines in human and animal health.
develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines and other interventions. | Antimicrobial resistance | Wikipedia | 336 | 1914 | https://en.wikipedia.org/wiki/Antimicrobial%20resistance | Biology and health sciences | Anti-infectives | Health |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.