In common usage, an antibiotic (from the Ancient Greek Ancient Greek is the historical stage in the development of the Greek language spanning the Archaic , Classical (c. 5th–4th centuries BC), and Hellenistic (c. 3rd century BC – 6th century AD) periods of ancient Greece and the ancient world. It is predated in the 2nd millennium BC by Mycenaean Greek. Its Hellenistic phase is known as Koine (&: ἀντί – anti, "against", and βίος – bios, "life") is a substance In chemistry, a chemical substance is a material with a specific chemical composition or compound A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together in a defined spatial arrangement by chemical bonds that kills bacteria The bacteria ( [bækˈtɪəriə] ; singular: bacterium)[α] are a large group of single-celled, prokaryote microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals. Bacteria are ubiquitous in every habitat on Earth, growing in soil, acidic hot springs, radioactive waste, or inhibits their growth.^[1] Antibiotics belong to the broader group of antimicrobial An antimicrobial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes (microbistatic). Disinfectants are antimicrobial substances used on non-living objects compounds, used to treat infections caused by microorganisms A microorganism or microbe is an organism that is microscopic (too small to be seen by the naked human eye). The study of microorganisms is called microbiology, a subject that began with Anton van Leeuwenhoek's discovery of microorganisms in 1675, using a microscope of his own design, including fungi A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. The Fungi (pronounced /ˈfʌndʒaɪ/ or /ˈfʌŋɡaɪ/) are classified as a kingdom that is separate from plants, animals and bacteria. One major difference is that fungal cells have cell and protozoa Protozoa is a subkingdom of microorganisms that are classified generally as unicellular non-fungal eukaryotes. Protozoans are a major component of the ecosystem.

The term "antibiotic" was coined by Selman Waksman Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics. A professor of biochemistry and microbiology at Rutgers University for four decades, his work led to in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.^[2] This original definition excluded naturally occurring substances that kill bacteria but are not produced by microorganisms (such as gastric juice Gastric juice is a strong acidic liquid, pH 1 to 3 in humans, which is close to being colourless. The hormone gastrin is released into the bloodstream when peptides are detected in the stomach. This causes gastric glands in the lining of the stomach to secrete gastric juice. Its main components are digestive enzymes pepsin and rennin , and hydrogen peroxide Hydrogen peroxide is naturally produced in organisms as a by-product of oxidative metabolism. Nearly all living things possess enzymes known as peroxidases, which harmlessly and catalytically decompose low concentrations of hydrogen peroxide to water and oxygen) and also excluded synthetic In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions. In modern laboratory usage, this tends to imply that the process is reproducible, reliable, and established to work in multiple antibacterial compounds such as the sulfonamides Sulfonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based on the antibacterial. Many antibiotics are relatively small molecules In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer. The term small molecule, especially within the field of pharmacology, is usually restricted to a molecule that also binds with high affinity to a biopolymer such as protein, nucleic acid, or with a molecular weight The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit(s) u (equal to 1/12 the mass of one atom of the isotope carbon-12). This is numerically equivalent to the relative molecular mass of a molecule, frequently referred to by the term molecular weight, which is the ratio of the mass of that less than 2000 Da The unified atomic mass unit or atomic mass unit , or dalton (Da) or, sometimes, universal mass unit (u), is a unit of mass used to express atomic and molecular masses. It is the approximate mass of a hydrogen atom, a proton, or a neutron.^{[citation needed]}

With advances in medicinal chemistry Medicinal or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology involved with designing, synthesizing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing, most antibiotics are now semisynthetic "Semisynthesis" or partial chemical synthesis is a type of chemical synthesis that uses compounds isolated from natural sources as starting materials. These natural biomolecules are usually large and complex molecules. This is opposed to a total synthesis where large molecules are synthesized from a stepwise combination of small and—modified chemically from original compounds found in nature,^[3] as is the case with beta-lactams β-lactam antibiotics are a broad class of antibiotics that include penicillin derivatives , cephalosporins (cephems), monobactams, and carbapenems, that is, any antibiotic agent that contains a β-lactam nucleus in its molecular structure. They are the most widely-used group of antibiotics (which include the penicillins Penicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections. Penicillins are still widely used today, though many types of bacteria are now, produced by fungi in the genus Penicillium Penicillium is a genus of ascomycetous fungi of major importance in the natural environment as well as food and drug production. It produces penicillin, a molecule that is used as an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the body, the cephalosporins The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium", and the carbapenems Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases. Carbapenem antibiotics were originally developed from thienamycin, a naturally-derived product of Streptomyces cattleya). Some antibiotics are still produced and isolated from living organisms, such as the aminoglycosides Several aminoglycosides function as antibiotics that are effective against certain types of bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin, streptomycin, tobramycin, and apramycin, and others have been created through purely synthetic means: the sulfonamides Sulfonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based on the antibacterial, the quinolones The quinolones, also referred to as fluoroquinolones, are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials, the first generation of which was derived from an attempt to create a synthetic form of chloroquine, which was used to treat malaria during World War II. Hans, and the oxazolidinones 2-Oxazolidone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring. In addition to this origin-based classification into natural, semisynthetic, and synthetic, antibiotics may be divided into two broad groups according to their effect on microorganisms: Those that kill bacteria are bactericidal A bactericide or bacteriocide is a substance that kills bacteria and, ideally, nothing else. Bactericides are either disinfectants, antiseptics or antibiotics agents, whereas those that only impair bacterial growth are known as bacteriostatic agents Bacteriostatic antibiotics limit the growth of bacteria by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism.

Contents 1 History of antibiotics 2 Antimicrobial pharmacodynamics 3 Antibiotic classes 3.1 Production 3.2 Administration 3.3 Side effects 4 Drug-drug interactions 4.1 Contraceptive pills 4.2 Alcohol 4.2.1 Specific effects 5 Antibiotic resistance 5.1 Antibiotic misuse 6 Beyond antibiotics: Treating multi-drug-resistant bacteria 6.1 Resistance-modifying agents 6.2 Phage Therapy 6.3 Bacteriocins 6.4 Nutrient withdrawal 6.5 Vaccines 6.6 Probiotics 7 Beyond antibiotics: treating non-bacterial infections 8 References 9 External links

History of antibiotics

This article may be confusing or unclear to readers. Please help clarify the article; suggestions may be found on the talk page. (January 2010)

See also: Timeline of antibiotics Categories: Technology timelines | Medicine timelines | History of medicine | Pharmacology Penicillin Penicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections. Penicillins are still widely used today, though many types of bacteria are now, the first natural antibiotic discovered by Alexander Fleming Sir Alexander Fleming was a Scottish biologist and pharmacologist. Fleming published many articles on bacteriology, immunology and chemotherapy. His best-known achievements are the discovery of the enzyme lysozyme in 1923 and the antibiotic substance penicillin from the fungus Penicillium notatum in 1928, for which he shared the Nobel Prize in in 1928.

Many treatments for infections prior to the beginning of the twentieth century were based on medicinal folklore Folk medicine refers to healing practices and ideas of body physiology and health preservation known to a limited segment of the population in a culture, transmitted informally as general knowledge, and practiced or applied by anyone in the culture having prior experience. Treatments for infection in ancient Chinese medicine Traditional Chinese Medicine, also known as TCM, includes a range of traditional medicine practices originating in China. Although well accepted in the mainstream of medical care throughout East Asia, it is considered an alternative medical system in much of the Western world using plants with antimicrobial properties were described over 2,500 years ago.^[4][5] Many other ancient cultures, including the ancient Egyptians Ancient Egyptian Medicine refers to the practices of healing common in Ancient Egypt from c. 33rd century BC until the Persian invasion of 525 BC. This medicine was highly advanced for the time, and included simple, non-invasive surgery, setting of bones and an extensive set of pharmacopoeia. While ancient Egyptian remedies are often and ancient Greeks The first known Greek medical school opened in Cnidus in 700 BC. Alcmaeon, author of the first anatomical work, worked at this school, and it was here that the practice of observing patients was established. Ancient Greek medicine centered around the theory of humours. The most important figure in ancient Greek medicine is the physician used molds Molds are fungi that grow in the form of multicellular filaments, called hyphae. In contrast, microscopic fungi that grow as single cells are called yeasts. A connected network of these tubular branching hyphae has multiple, genetically identical nuclei and is considered a single organism, referred to as a colony or in more technical terms a and plants to treat infections An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the host and can lead to chronic wounds, gangrene, loss.^[6][7] The discovery of the natural antibiotics produced by microorganisms stemmed from earlier work on the observation of antibiosis between micro-organisms. Louis Pasteur Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of disease. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies. His experiments supported the germ theory of disease. He was best known to the general observed that, "if we could intervene in the antagonism observed between some bacteria, it would offer ‘perhaps the greatest hopes for therapeutics’".^[8] Synthetic antibiotic chemotherapy as a science and the story of antibiotic development began in Germany with Paul Ehrlich Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus". He coined the term chemotherapy and popularized the concept of a magic bullet, a German medical scientist in the late 1880s.^[9] Scientific endeavours to understand the science behind what caused these diseases, the development of synthetic antibiotic chemotherapy, the isolation of the natural antibiotics marked milestones in antibiotic development.^[10]

Originally known as antibiosis, antibiotics were drugs that had actions against bacteria. The term antibiosis, which means "against life," was introduced by the French bacteriologist Vuillemin He studied medicine at the University of Nancy in 1884, and from 1895 to 1932 he was Professor of Natural History at the medical faculty there. He described the genera Spinalia and Zygorhynchus as a descriptive name of the phenomenon exhibited by these drugs.^[9] (Antibiosis was first described in 1877 in bacteria when Louis Pasteur Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of disease. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies. His experiments supported the germ theory of disease. He was best known to the general and Robert Koch Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis (1877), the Tuberculosis bacillus (1882) and the Vibrio cholerae (1883) and for his development of Koch's postulates. He was awarded the Nobel Prize in Physiology or Medicine for his tuberculosis findings in 1905. He is considered one of the observed that an airborne bacillus could inhibit the growth of Bacillus anthracis Bacillus anthracis is a Gram-positive spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions[citation needed]. It is the only bacterium with a protein capsule , and the only pathogenic bacteria to carry its own adenylyl cyclase.^[11]). These drugs were later renamed antibiotics by Selman Waksman Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics. A professor of biochemistry and microbiology at Rutgers University for four decades, his work led to, an American microbiologist in 1942.^[2][9]

Bacterial antagonism of Penicillium spp. were first described in England by John Tyndall John Tyndall FRS was a prominent 19th century physicist. His initial scientific fame arose in the 1850s from his study of diamagnetism. Later he studied thermal radiation, and produced a number of discoveries about processes in the atmosphere. Tyndall published seventeen books, which brought state-of-the-art 19th century experimental physics to a in 1875.^[8] The significance to antibiotic discovery was not realized until the work of Ehrlich Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus". He coined the term chemotherapy and popularized the concept of a magic bullet on synthetic antibiotic chemotherapy, which marked the birth of the antibiotic revolution. Ehrlich noted that certain dyes would bind to and color human, animal, or bacterial cells, while others did not. He then extended the idea that it might be possible to make certain dyes or chemicals that would act as a magic bullet or selective drug that would bind to and kill bacteria while not harming the human host. After much experimentation, screening hundreds of dyes against various organisms, he discovered a medicinally useful drug, the man-made antibiotic, Salvarsan Arsphenamine, also known as Salvarsan and 606, is a drug that was used beginning in the 1910s to treat syphilis and trypanosomiasis. It is an organoarsenic compound and was the first modern chemotherapeutic agent.^[9][12][13] In 1928 Fleming made an important observation concerning the antibiosis by penicillin. Fleming postulated that the effect was mediated by a yet-unidentified antibiotic-like compound that could be exploited. Although he initially characterized some of its antibiotic properties, he did not pursue its development.^[14][15] In the meantime, another synthetic antibacterial antibiotic Prontosil was developed and manufactured for commercial use by Domagk in 1932.^[13] Prontosil Prontosil, the first commercially available antibacterial antibiotic , was developed by a research team at the Bayer Laboratories of the IG Farben conglomerate in Germany. The discovery and development of this first sulfonamide drug opened a new era in medicine, the first commercially available antibacterial antibiotic, was developed by a research team led by Gerhard Domagk Gerhard Johannes Paul Domagk was a German pathologist and bacteriologist credited with the discovery of Sulfonamidochrysoidine (KI-730) – the first commercially available antibiotic (marketed under the brand name Prontosil) – for which he received the 1939 Nobel Prize in Physiology or Medicine (who received the 1939 Nobel Prize for Medicine for his efforts) at the Bayer Laboratories of the IG Farben conglomerate in Germany. Prontosil had a relatively broad effect against Gram-positive cocci but not against enterobacteria. The discovery and development of this first sulfonamide drug opened the era of antibiotics. In 1939, discovery by Rene Dubos of the first naturally derived antibiotic-like substance named gramicidin from B. brevis. It was one of the first commercially manufactured antibiotics in use during World War II to prove highly effective in treating wounds and ulcers.^[16] Florey and Chain succeeded in purifying penicillin. The purified antibiotic displayed antibacterial activity against a wide range of bacteria. It also had low toxicity and could be taken without causing adverse effects. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic antibiotic class available at the time, the sulfonamides. The discovery of such a powerful antibiotic was unprecedented. The development of penicillin led to renewed interest in the search for antibiotic compounds with similar capabilities.^[17] Because of their discovery of penicillin Ernst Chain, Howard Florey and Alexander Fleming shared the 1945 Nobel Prize in Medicine. Florey credited Dubos with pioneering the approach of deliberately, systematically searching for antibacterial compounds. Such a methodology had led to the discovery of gramicidin, which revived Florey's research in penicillin.^[16]

Antimicrobial pharmacodynamics

Main article: Antimicrobial pharmacodynamics Testing the susceptibility of Staphylococcus aureus to antibiotics by the Kirby-Bauer disk diffusion method. Antibiotics diffuse out from antibiotic-containing disks and inhibit growth of S. aureus, resulting in a zone of inhibition

The assessment of the activity of an antibiotic is crucial to the successful outcome of antimicrobial therapy. Non-microbiological factors such as host defense mechanisms, the location of an infection, the underlying disease as well as the intrinsic pharmacokinetic and pharmacodynamic properties of the antibiotic.^[18] Fundamentally, antibiotics are classified as either having lethal (bactericidal) action against bacteria or are bacteriostatic, preventing bacterial growth. The bactericidal activity of antibiotics may be growth phase-dependent, and, in most but not all cases, the action of many bactericidal antibiotics requires ongoing cell activity and cell division for the drugs' killing activity.^[19] These classifications are based on laboratory behavior; in practice, both of these are capable of ending a bacterial infection.^[18][20]'In vitro' characterisation of the action of antibiotics to evaluate activity measure the minimum inhibitory concentration and minimum bactericidal concentration of an antimicrobial and are excellent indicators of antimicrobial potency.^[21] However, in clinical practice, these measurements alone are insufficient to predict clinical outcome. By combining the pharmacokinetic profile of an antibiotic with the antimicrobial activity, several pharmacological parameters appear to be significant markers of drug efficacy.^[22][23] The activity of antibiotics may be concentration-dependent and their characteristic antimicrobial activity increases with progressively higher antibiotic concentrations.^[24] They may also be time-dependent, where their antimicrobial activity does not increase with increasing antibiotic concentrations; however, it is critical that a minimum inhibitory serum concentration is maintained for a certain length of time.^[24] A laboratory evaluation of the killing kinetics of the antibiotic using kill curves is useful to determine the time- or concentration-dependence of .^[18]

Antibiotic classes

Main article: List of antibiotics Molecular targets of antibiotics on the bacteria cell

Antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most antibiotics target bacterial functions or growth processes.^[9] Antibiotics that target the bacterial cell wall (penicillins, cephalosporins), or cell membrane (polymixins), or interfere with essential bacterial enzymes (quinolones, sulfonamides) are usually bactericidal in nature. Those that target protein synthesis, such as the aminoglycosides, macrolides, and tetracyclines, are usually bacteriostatic.^[25] Further categorization is based on their target specificity: "Narrow-spectrum" antibiotics target particular types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. In the last few years, three new classes of antibiotics have been brought into clinical use. This follows a 40-year hiatus in discovering new classes of antibiotic compounds. These new antibiotics are of the following three classes: cyclic lipopeptides (daptomycin), glycylcyclines (tigecycline), and oxazolidinones (linezolid). Tigecycline is a broad-spectrum antibiotic, whereas the two others are used for Gram-positive infections. These developments show promise as a means to counteract the bacterial resistance to existing antibiotics.

Production

Main article: Production of antibiotics

Since the first pioneering efforts of Florey and Chain in 1939, the importance of antibiotics to medicine has led to much research into discovering and producing them. The process of production usually involves the screening of wide ranges of microorganisms, and their testing and modification. Production is carried out using fermentation, usually in strongly aerobic form.

Administration

Oral antibiotics are simply ingested, while intravenous antibiotics are used in more serious cases, such as deep-seated systemic infections. Antibiotics may also sometimes be administered topically, as with eye drops or ointments.

Side effects

Although antibiotics are, in general, considered safe and well-tolerated, they have been associated with a wide range of adverse effects.^[26] Side-effects are many and varied, and can be very serious depending on the antibiotics used and the microbial organisms targeted. The safety profiles of newer medications may not be as well established as those that have been in use for many years.^[26] Adverse effects can range from fever and nausea to major allergic reactions including photodermatitis and anaphylaxis.^{[citation needed]} One of the more common side-effects is diarrhea, sometimes caused by the anaerobic bacterium Clostridium difficile, which results from the antibiotic's disrupting the normal balance of the intestinal flora,^[27] Such overgrowth of pathogenic bacteria may be alleviated by ingesting probiotics during a course of antibiotics.^{[citation needed]} An antibiotic-induced disruption of the population of the bacteria normally present as constituents of the normal vaginal flora may also occur, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area.^[28] Other side-effects can result from interaction with other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid. Certain antibiotics administered by IV (e.g.aminoglycosides, vacomycin) can cause significant permanent hearing loss. ^[29]

Drug-drug interactions

Contraceptive pills

It has been hypothesized that interference of some antibiotics with the efficiency of birth control pills is thought to occur in two ways. Modification of the intestinal flora may result in reduced absorption of estrogens. Second, induction of hepatic liver enzymes causing them to metabolize the pill's active ingredients faster may affect the pill's usefulness.^[30] However, the majority of studies indicate that antibiotics do not interfere with contraception.^[30] Even though a small percentage of women may experience decreased effectiveness of birth control pills while taking an antibiotic, the failure rate is comparable to the failure rate of those taking the pill.^[31] Moreover, there have been no studies that have conclusively demonstrated that disruption of the gut flora affects contraception.^[32][33] Interaction with the combined oral contraceptive pill through induction of hepatic enzymes by the broad-spectrum antibiotic rifampicin has been shown to occur. It is recommended that extra contraceptive measures are applied during antimicrobial therapy using these antimicrobials.^[30]

Alcohol

Interactions between alcohol and antibiotics vary depending on the specific antibiotic, and, in some cases, can cause severe side-effects and decrease effectiveness.

"It is sensible to avoid drinking alcohol when taking medication. However, it is unlikely that drinking alcohol in moderation will cause problems if you are taking most "common" antibiotics." However, there are specific types of antibiotics with which alcohol should be avoided completely, because of a serious side-effects.^[34]

Because of the risks of side-effects and effectiveness, one should check the specific indications on the specific antibiotic, but there is no categorical danger in mixing alcohol and [some] antibiotics. Despite the lack of a categorical counterindication, the belief that alcohol and antibiotics should never be mixed is widespread, as indicated in a survey in one British clinic.

"[P]atients often assume that they should avoid alcohol when taking any antibiotics. ...this belief has no foundation."^[35]

One potential source of the myth is from STD clinics in the 1950s and 1960s.^[36] Doctors gave the advice for moral reasons as they were worried that alcohol would reduce the inhibitions of sufferers and lead to further spread of diseases such as gonorrhoea.^[37] It has been suggested, but not corroborated, that the origin of this myth centers on the fact that, during World War II, penicillin was in short supply and was recycled from urine; convalescing soldiers that drank beer produced a greater volume of urine, and, thus, were banned from drinking beer, leading to the belief that alcohol interacted poorly with antibiotics.^[35]

Specific effects

By way of side-effects, certain antibiotics, including metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting metabolism by acetaldehyde dehydrogenase, leading to serious side-effects, which include severe vomiting, nausea, and shortness of breath. Alcohol consumption while taking such antibiotics is, therefore, prohibited.^[34]

Other effects of alcohol involve the activity of liver enzymes, which break down the antibiotics.^[38] In addition, serum levels of doxycycline and erythromycin succinate^{[clarification needed]} may, in certain circumstances, be significantly reduced by alcohol consumption.^[39] This is particularly important, since these drugs are bacteriostatic and require a sustained level of the drug in the body to be effective: Increased metabolism and clearance would result in diminished pharmacotherapeutic effect.

Alcohol can interfere with the activity or metabolization of antibiotics ^[40]

Antibiotic resistance

Main article: Antibiotic resistance SEM depicting methicillin-resistant Staphylococcus aureus bacteria.

The emergence of antibiotic resistance is an evolutionary process that is based on selection for organisms that have enhanced ability to survive doses of antibiotics that would have previously been lethal.^[41] Antibiotics like Penicillin and Erythromycin, which used to be one-time miracle cures are now less effective because bacteria have become more resistant.^[42] Antibiotics themselves act as a selective pressure that allows the growth of resistant bacteria within a population and inhibits susceptible bacteria.^[43] Antibiotic selection of pre-existing antibiotic resistant mutants within bacterial populations was demonstrated in 1943 by the Luria–Delbrück experiment.^[44] Survival of bacteria often results from an inheritable resistance.^[45] Any antibiotic resistance may impose a biological cost. Spread of antibiotic-resistant bacteria may be hampered by reduced fitness associated with the resistance, which is disadvantageous for survival of the bacteria when antibiotic is not present. Additional mutations, however, may compensate for this fitness cost and aids the survival of these bacteria.^[46]

The underlying molecular mechanisms leading to antibiotic resistance can vary. Intrinsic resistance may naturally occur as a result of the bacteria's genetic makeup.^[47] The bacterial chromosome may fail to encode a protein that the antibiotic targets. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA.^[47] Antibiotic-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibiotic-resistant strains.^[48][49] The spread of antibiotic resistance mechanisms occurs through vertical transmission of inherited mutations from previous generations and genetic recombination of DNA by horizontal genetic exchange.^[45] Antibiotic resistance is exchanged between different bacteria by plasmids that carry genes that encode antibiotic resistance that may result in co-resistance to multiple antibiotics.^[45][50] These plasmids can carry different genes with diverse resistance mechanisms to unrelated antibiotics but because they are located on the same plasmid multiple antibiotic resistance to more than one antibiotic is transferred.^[50] On the other hand, cross-resistance to other antibiotics within the bacteria results when the same resistance mechanism is responsible for resistance to more than one antibiotic is selected for.^[50]

Antibiotic misuse

This poster from the U.S. Centers for Disease Control and Prevention "Get Smart" campaign, intended for use in doctor's offices and other healthcare facilities, warns that antibiotics do not work for viral illnesses such as the common cold.

The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them.^[51] —Paul L. Marino, The ICU Book

Inappropriate antibiotic treatment and overuse of antibiotics have been a contributing factor to the emergence of resistant bacteria. The problem is further exacerbated by self-prescribing of antibiotics by individuals without the guidelines of a qualified clinician and the non-therapeutic use of antibiotics as growth promoters in agriculture.^[52] Antibiotics are frequently prescribed for indications in which their use is not warranted, an incorrect or sub-optimal antibiotic is prescribed or in some cases for infections likely to resolve without treatment.^[26][52] The overuse of antibiotics like penicillin and erythromycin, which used to be one-time miracle cures, were associated with emerging resistance since the 1950s.^[42][53] Therapeutic usage of antibiotics in hospitals has been seen to be associated with increases in multi-antibiotic-resistant bacteria.^[53]

Common forms of antibiotic misuse include excessive use of prophylactic antibiotics in travelers, failure to take into account the patient's weight and history of prior antibiotic use when prescribing, since both can strongly affect the efficacy of an antibiotic prescription, failure to take the entire prescribed course of the antibiotic, failure to prescribe or take the course of treatment at fairly precise correct daily intervals (e.g., "every 8 hours" rather than merely "3x per day"), or failure to rest for sufficient recovery to allow clearance of the infecting organism. These practices may facilitate the development of bacterial populations with antibiotic resistance. Inappropriate antibiotic treatment is another common form of antibiotic misuse. A common example is the prescription and use of antibiotics to treat viral infections such as the common cold that have no effect. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who they believed expected them, although they correctly identified only about 1 in 4 of those patients".^[54] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescribing of antibiotics.^[55] Delaying antibiotics for 48 hours while observing for spontaneous resolution of respiratory tract infections may reduce antibiotic usage; however, this strategy may reduce patient satisfaction.^[56]

Several organizations concerned with antimicrobial resistance are lobbying to improve the regulatory climate.^[52] Approaches to tackling the issues of misuse and overuse of antibiotics by the establishment of the U.S. Interagency Task Force on Antimicrobial Resistance, which aims to actively address the problem antimicrobial resistance, are being organised and coordinated by the US Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and the National Institutes of Health (NIH), as well as other federal agencies.^[57] An NGO campaign group is Keep Antibiotics Working.^[58] In France, an "Antibiotics are not automatic" government campaign starting in 2002 led to a marked reduction of unnecessary antibiotic prescriptions, especially in children.^[59] In the United Kingdom, there are NHS posters in many doctors' surgeries indicating that 'no amount of antibiotics will get rid of your cold', with many patients specifically requesting antibiotics from their doctor inappropriately, believing they treat viral infections.

In agriculture, associated antibiotic resistance with the non-therapeutic use of antibiotics as growth promoters in animals resulted in their restricted use in the UK in the 1970 (Swann report 1969). At the current time, there is a EU-wide ban on the non-therapeutic use of antibiotics as growth promoters. It is estimated that greater than 70% of the antibiotics used in U.S. are given to feed animals (e.g., chickens, pigs, and cattle) in the absence of disease.^[60] Antibiotic use in food animal production has been associated with the emergence of antibiotic-resistant strains of bacteria including Salmonella spp., Campylobacter spp., Escherichia coli, and Enterococcus spp.^[61][62] Evidence from some US and European studies suggest that these resistant bacteria cause infections in humans that do not respond to commonly prescribed antibiotics. In response to these practices and attendant problems, several organizations (e.g., The American Society for Microbiology (ASM), American Public Health Association (APHA) and the American Medical Association (AMA)) have called for restrictions on antibiotic use in food animal production and an end to all non-therapeutic uses.^{[citation needed]} However, delays in regulatory and legislative actions to limit the use of antibiotics are common, and may include resistance to these changes by industries using or selling antibiotics, as well as time spent on research to establish causal links between antibiotic use and emergence of untreatable bacterial diseases. Two federal bills (S.742^[63] and H.R. 2562^[64]) aimed at phasing out non-therapeutic antibiotics in US food animal production were proposed but not passed.^[63][64] 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 (APHA).^[65] The EU has banned the use of antibiotics as growth promotional agents since 2003.^[66]

Beyond antibiotics: Treating multi-drug-resistant bacteria

Multi-drug-resistant organisms (MDRO), in general, refer to bacteria that are not affected by the clinical doses of classical antibiotics, in particular, the antibiotics used to treat them until recently. The rise of these organisms has created a need for alternative antibacterial therapies.

Resistance-modifying agents

One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistance. These so-called resistance-modifying agents may target and inhibit MDR mechanisms, rendering the bacteria susceptible to antibiotics to which they were previously resistant. These compounds targets include among others

• Efflux inhibition(Phe-Arg-β-naphthylamide)^[67]
• Beta-Lactamase inhibitors - Including Clavulanic acid and Sulbactam

Phage Therapy

Phage therapy, the use of a particular group of viruses capable of invading bacteria known as phages to treat bacterial infections.^[68][69] Phage are commonly a part of the ecology surrounding bacteria and provide substantial population control of bacteria in the intestine, the ocean, the soil, and other environments.^[70] The therapy was in use during the 1920s and 1930s on humans in the US, Western Europe, and Eastern Europe. The success of these therapies is largely anecdotal, and rigorous scientific studies in the form of clinical trials commonly used to evaluate the efficacy of new medications on the efficacy of phage therapy are limited^[69] The original publications into phage therapy are also generally inaccessible, even to persons with Russian language fluency. With the discovery of penicillin in the 1940s, Europe and the US abandoned research into phage therapy and began work to develop antibiotics as a therapeutic strategy combate bacterial infections. However, in the former Soviet Union, phage therapies continued to be studied in the Eliava Institute of Bacteriophage, Microbiology & Virology, Republic of Georgia.^[71] With the development of antibiotic-resistant bacteria, there was a renewed interest in development of phage therapy as a viable alternative to antibiotic treatment of bacterial infection in western medicine.^[72] Research is currently ongoing; companies (Intralytix, Novolytics, UK, Gangagen, India), universities, and foundations in North America and Europe are currently researching phage therapies.^{[72][73][74][75]} However, concerns about genetic engineering in freely released viruses currently limit certain aspects of phage therapy. One result is attempts to use phage in ways other than to directly infect the bacteria.^[76][77] While bacteriophage and related therapies provide a possible solution to aspects of antibiotic resistance, much more research is needed to realise their potential^[69]

Bacteriocins

Bacteriocins are also a growing alternative to the classic small-molecule antibiotics.^[78] Different classes of bacteriocins have different potential as therapeutic agents. Small molecule bacteriocins (microcins, for example, and lantibiotics) may be similar to the classic antibiotics; colicin-like bacteriocins are more likely to be narrow-spectrum, demanding new molecular diagnostics prior to therapy but also not raising the spectre of resistance to the same degree. One drawback to the large-molecule antibiotics is that they have relative difficulty crossing membranes and travelling systemically throughout the body. For this reason, they are most often proposed for application topically or gastrointestinally.^[79] Because bacteriocins are peptides, they are more readily engineered than small molecules.^[80] This may permit the generation of cocktails and dynamically improved antibiotics that are modified to overcome resistance.

Nutrient withdrawal

Nutrient withdrawal is a potential strategy for replacing or supplementing antibiotics. The restriction of iron availability is one way the human body limits bacterial proliferation.^[81] Mechanisms for freeing iron from the body (such as toxins and siderophores) are common among pathogens. Building on this dynamic, various research groups are attempting to produce novel chelators that would withdraw iron otherwise available to pathogens (bacterial,^[82] fungal ^[83] and parasitic ^[84]). This is distinct from chelation therapy for conditions other than bacterial infections - including successful treatment for iron overload.

Vaccines

Vaccines are a commonly suggested method for combating MDRO infections. They actually fit within a larger class of therapies that rely on immune modulation or augmentation. These therapies either excite or reinforce the natural immune competency of the infected or susceptible host, leading to the activity of macrophages, the production of antibodies, inflammation, or other classic immune reactions.

Just as the macrophage engulfs and consumes bacteria, various forms of biotherapy have been suggested that employ organisms to consume the pathogens. This includes the employment of protozoa ^[85] and maggot therapy.

Probiotics

Probiotics are another alternative that goes beyond traditional antibiotics by employing a live culture, which may, in theory, establish itself as a symbiont—competing, inhibiting, or simply interfering with colonization by pathogens.^[86]

Beyond antibiotics: treating non-bacterial infections

This section needs attention from an expert on the subject. See the talk page for details. WikiProject Pharmacology or the Pharmacology Portal may be able to help recruit an expert. (July 2009)

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The comparative ease of identifying compounds that safely cured bacterial infections was more difficult to duplicate in treatments of fungal and viral infections. Antibiotic research led to great strides in the knowledge of biochemistry, establishing large differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. This explained the observation that many compounds that are toxic to bacteria are non-toxic to human cells. In contrast, the basic biochemistries of the fungal cell and the mammalian cell are much more similar. Most antifungal drugs have targeted steps in the synthesis of the fungal cell membrane (e.g., imidazole, triazole, and allylamine antifungals) or target components of the formed cell wall (e.g., polyene antifungals). However, toxicity is not fully avoided in the case of polyene antifungals since they can target human membrane cholesterol, mistaking it for fungal ergosterol.

This restricts the development and use of therapeutic compounds that attack a fungal cell, while not harming mammalian cells. Similar problems exist in antibiotic treatments of viral diseases. Human viral metabolic biochemistry is very closely similar to human biochemistry, and the possible targets of antiviral compounds are restricted to very few components unique to a mammalian virus.

For related articles, see fungicide, antifungal drug, and antiviral drug.

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External links

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• Antibiotic at the Open Directory Project

Pharmacology: Major drug groups Gastrointestinal tract/metabolism (A) stomach acid (Antacids, H2 antagonists, Proton pump inhibitors) • Antiemetics • Laxatives • Antidiarrhoeals/Antipropulsives • Anti-obesity drugs • Anti-diabetics • Vitamins • Dietary minerals Blood and blood forming organs (B) Antithrombotics (Antiplatelets, Anticoagulants, Thrombolytics/fibrinolytics) • Antihemorrhagics (Platelets, Coagulants, Antifibrinolytics) Cardiovascular system (C) cardiac therapy/antianginals (Cardiac glycosides, Antiarrhythmics, Cardiac stimulants) Antihypertensives • Diuretics • Vasodilators • Beta blockers • Calcium channel blockers • renin-angiotensin system (ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors) Antihyperlipidemics (Statins, Fibrates, Bile acid sequestrants) Skin (D) Emollients • Cicatrizants • Antipruritics • Antipsoriatics • Medicated dressings Genitourinary system (G) Hormonal contraception • Fertility agents • SERMs • Sex hormones Endocrine system (H) Hypothalamic-pituitary hormones • Corticosteroids (Glucocorticoids, Mineralocorticoids) • Sex hormones • Thyroid hormones/Antithyroid agents Infections and infestations (J, P, QI) Antibiotics (Antimycobacterials) • Antifungals • Antivirals • Antiparasitics (Antiprotozoals, Anthelmintics) • Ectoparasiticides • Intravenous immunoglobulin • Vaccines Malignant disease (L01-L02) Anticancer agents (Antimetabolites, Alkylating, Spindle poisons, Antineoplastic, Topoisomerase inhibitors) Immune disease (L03-L04) Immunomodulators (Immunostimulants, Immunosuppressants) Muscles, bones, and joints (M) Anabolic steroids • Anti-inflammatories (NSAIDs) • Antirheumatics • Corticosteroids • Muscle relaxants • Bisphosphonates Brain and nervous system (N) Analgesics • Anesthetics (General, Local) • Anorectics • Anti-ADHD Agents • Antiaddictives • Anticonvulsants • Antidementia Agents • Antidepressants • Antimigraine Agents • Antiparkinson's Agents • Antipsychotics • Anxiolytics • Depressants • Entactogens • Entheogens • Euphoriants • Hallucinogens (Psychedelics, Dissociatives, Deliriants) • Hypnotics/Sedatives • Mood Stabilizers • Neuroprotectives • Nootropics • Neurotoxins • Orexigenics • Serenics • Stimulants • Wakefulness-Promoting Agents Respiratory system (R) Decongestants • Bronchodilators • Cough medicines • H1 antagonists Sensory organs (S) Ophthalmologicals • Otologicals Other ATC (V) Antidotes • Contrast media • Radiopharmaceuticals • Dressings

Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ) 30S Aminoglycosides (initiation inhibitors) -mycin (Streptomyces) Streptomycin Neomycin (Framycetin, Paromomycin, Ribostamycin) Kanamycin (Amikacin, Arbekacin, Bekanamycin, Dibekacin, Tobramycin) Spectinomycin# · Hygromycin B Paromomycin -micin (Micromonospora) Gentamicin# (Netilmicin, Sisomicin, Isepamicin) Verdamicin Astromicin Tetracycline antibiotics (tRNA binding) Tetracyclines Doxycycline# •Chlortetracycline • Clomocycline • Demeclocycline • Lymecycline • Meclocycline • Metacycline • Minocycline • Oxytetracycline • Penimepicycline • Rolitetracycline • Tetracycline Glycylcyclines Tigecycline 50S Oxazolidinone (initiation inhibitors) Linezolid • Torezolid · Eperezolid · Posizolid · Radezolid · Peptidyl transferase Amphenicols Chloramphenicol# · Azidamfenicol · Thiamphenicol · Florfenicol Pleuromutilins Retapamulin · Tiamulin · Valnemulin MLS (transpeptidation/translocation) Macrolides Erythromycin# · Azithromycin# · Spiramycin · Midecamycin · Oleandomycin · Roxithromycin · Josamycin · Troleandomycin · Clarithromycin · Miocamycin · Rokitamycin · Dirithromycin · Flurithromycin · Ketolide (Telithromycin, Cethromycin) Lincosamides Clindamycin# · Lincomycin Streptogramins Pristinamycin · Quinupristin/dalfopristin · Virginiamycin EF-G Steroid antibacterials Fusidic acid #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III : BAC () /()/()/ drug(, , , , )

Antibacterials: cell envelope antibiotics (J01C-J01D) Internal to membrane/ (inhibit peptidoglycan subunit synthesis and transport) NAM synthesis inhibition (Fosfomycin) · DADAL/AR inhibitors (Cycloserine) · bactoprenol inhibitors (Bacitracin) Glycopeptide/ (inhibit PG chain elongation) Vancomycin# (Oritavancin, Telavancin) · Teicoplanin (Dalbavancin) · Ramoplanin β-lactams/ (inhibit cross-links with PBP) Penicillins/ (penams) Extended sp. aminopenicillins: Amoxicillin# · Ampicillin# (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin) · Epicillin carboxypenicillins: Carbenicillin (Carindacillin) · Ticarcillin · Temocillin ureidopenicillins: Azlocillin · Piperacillin · Mezlocillin other: Mecillinam (Pivmecillinam) · Sulbenicillin Narrow sp. β-lactamase sensitive Benzylpenicillin (G)#: Clometocillin · Benzathine benzylpenicillin# · Procaine benzylpenicillin# · Azidocillin · Penamecillin Phenoxymethylpenicillin (V)#: Propicillin · Benzathine phenoxymethylpenicillin · Pheneticillin β-lactamase resistant Cloxacillin# (Dicloxacillin, Flucloxacillin) · Oxacillin · Meticillin · Nafcillin Penems Faropenem Carbapenems Biapenem · Doripenem · Ertapenem · Imipenem · Meropenem · Panipenem Cephalosporins/ (cephems) 1st (P Ec K) Cefazolin# · Cefacetrile · Cefadroxil · Cefalexin · Cefaloglycin · Cefalonium · Cefaloridine · Cefalotin · Cefapirin · Cefatrizine · Cefazedone · Cefazaflur · Cefradine · Cefroxadine · Ceftezole 2nd (H E N) Cefaclor · Cefamandole · Cefminox · Cefonicid · Ceforanide · Cefotiam · Cefprozil · Cefbuperazone · Cefuroxime · Cefuzonam · cephamycin (Cefoxitin, Cefotetan, Cefmetazole) · carbacephem (Loracarbef) 3rd Cefixime# · Ceftazidime# · Ceftriaxone# · Cefcapene · Cefdaloxime · Cefdinir · Cefditoren · Cefetamet · Cefmenoxime · Cefodizime · Cefoperazone · Cefotaxime · Cefpimizole · Cefpiramide · Cefpodoxime · Cefsulodin · Cefteram · Ceftibuten · Ceftiolene · Ceftizoxime · oxacephem (Flomoxef, Latamoxef ‡) 4th Cefepime · Cefozopran · Cefpirome · Cefquinome 5th Ceftobiprole · Ceftaroline Veterinary Ceftiofur · Cefquinome · Cefovecin Monobactams Aztreonam · Tigemonam · Carumonam β-lactamase inhibitors penam (Sulbactam, Tazobactam) · clavam (Clavulanic acid) Combinations Co-amoxiclav (Amoxicillin/clavulanic acid)# · Imipenem/cilastatin# · Ampicillin/sulbactam (Sultamicillin) · Piperacillin/tazobactam Other polymyxins/detergent (Colistin, Polymyxin B) · depolarizing (Daptomycin) · hydrolyze NAM-NAG (Lysozyme) #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III : BAC () /()/()/ drug(, , , , )

Antibacterials: nucleic acid inhibitors (J01E, J01M) Antifolates (inhibits purine metabolism, thereby inhibiting DNA and RNA synthesis) DR inhibitor 2,4-Diaminopyrimidine (Trimethoprim#, Brodimoprim, Tetroxoprim, Iclaprim†) Sulfonamides (DS inhibitor) Short- acting Sulfaisodimidine · Sulfamethizole · Sulfadimidine · Sulfapyridine · Sulfafurazole · Sulfanilamide (Prontosil) · Sulfathiazole · Sulfathiourea Intermediate- acting Sulfamethoxazole · Sulfadiazine# · Sulfamoxole Long- acting Sulfadimethoxine · Sulfalene · Sulfametomidine · Sulfametoxydiazine · Sulfamethoxypyridazine · Sulfaperin · Sulfamerazine · Sulfaphenazole · Sulfamazone Other/ungrouped sulfanilamide (Sulfacetamide, Sulfametrole) Combinations Sulfamethoxazole and trimethoprim# Topoisomerase inhibitors/ quinolones/ (inhibits DNA replication) 1st generation Cinoxacin‡ · Flumequine · Nalidixic acid · Oxolinic acid · Pipemidic acid · Piromidic acid · Rosoxacin Fluoroquinolones 2nd generation Ciprofloxacin# · Enoxacin‡ · Fleroxacin‡ · Lomefloxacin · Nadifloxacin · Ofloxacin · Norfloxacin · Pefloxacin · Rufloxacin 3rd generation Balofloxacin · Grepafloxacin‡ · Levofloxacin · Pazufloxacin · Sparfloxacin‡ · Temafloxacin‡ · Tosufloxacin 4th generation Besifloxacin · Clinafloxacin† · Garenoxacin · Gemifloxacin · Moxifloxacin · Gatifloxacin‡ · Sitafloxacin · Trovafloxacin‡/Alatrofloxacin‡ · Prulifloxacin Veterinary Danofloxacin · Difloxacin · Enrofloxacin · Ibafloxacin · Marbofloxacin · Orbifloxacin · Pradofloxacin · Sarafloxacin Related agents (DG) Aminocoumarins: Novobiocin Anaerobic DNA inhibitors Nitro- imidazole derivatives Metronidazole# · Tinidazole · Ornidazole Nitrofuran derivatives Furazolidone‡ · Nitrofurantoin# · Nifurtoinol RNA synthesis Rifamycins/ RNA polymerase Rifampicin · Rifabutin · Rifapentine · Rifaximin #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III : BAC () /()/()/ drug(, , , , )

Antibacterials: others (J01X) Other/ungrouped bornane: Xibornol cresol: Clofoctol polyamine: Methenamine alpha hydroxy acid: Mandelic acid nitroquinoline: Nitroxoline pyran/fatty acid: Isoleucine-tRNA ligase inhibitors (Mupirocin)

Infectious disease Pathogens Bacteria · Viruses · Fungi · Protozoan infection · Helminths · Prions Disciplines Microbiology · Bacteriology · Virology · Mycology · Parasitology · Medical entomology People Ignaz Semmelweis · Louis Pasteur · Robert Koch · Alexander Fleming Diseases Malaria · Tuberculosis · AIDS · Influenza Special topics Vaccination · Antibiotics · Pandemic · Eradication · Zoonosis · Transmission (Horizontal, Vertical)

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