antibiotic

抗生物質 　 　 　

WordNet

1. a chemical substance derivable from a mold or bacterium that can kill microorganisms and cure bacterial infections; "when antibiotics were first discovered they were called wonder drugs" (同)antibiotic drug
2. of or relating to antibiotic drugs
3. any drug that destroys bacteria or inhibits their growth (同)antibacterial_drug, bactericide
4. destroying bacteria or inhibiting their growth
5. capable of destroying or inhibiting the growth of disease-causing microorganisms (同)antimicrobic

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1. 抗生物質(ペニシリン,ストレプトマイシンなど) / 抗生[物質]の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/12 06:03:30」(JST)

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This article is about treatment of bacterial infection. For antitumor antibiotics, see Chemotherapy § Cytotoxic antibiotics.

Testing the susceptibility of Staphylococcus aureus to antibiotics by the Kirby-Bauer disk diffusion method – antibiotics diffuse from antibiotic-containing disks and inhibit growth of S. aureus, resulting in a zone of inhibition.

Antibiotics, also called antibacterials, are a type of antimicrobial drug used in the treatment and prevention of bacterial infection. 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 common cold or influenza, and may be harmful when taken inappropriately.

In 1928, Alexander Fleming identified penicillin, the first chemical compound with antibiotic properties. Fleming was working on a culture of disease-causing bacteria when he noticed the spores of little green mold in one of his culture plates. He observed that the presence of the mold killed or prevented the growth of the bacteria.

Antibiotics revolutionized medicine in the 20th century, and have together with vaccination led to the near eradication of diseases such as tuberculosis in the developed world. Their effectiveness and easy access led to overuse, especially in livestock raising, prompting bacteria to develop resistance. This has led to widespread problems with antimicrobial and antibiotic resistance, so much as to prompt the World Health Organization to classify antimicrobial resistance as a "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".

The era of antibacterial chemotherapy began with the discovery of arsphenamine, first synthesized by Alfred Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first systemically active antibacterial drug, prontosil was discovered in 1933 by Gerhard Domagk, for which he was awarded the 1939 Nobel Prize. All classes of antibiotics in use today were first discovered prior to the mid 1980s.

Sometimes the term antibiotic is used to refer to any substance used against microbes, synonymous to antimicrobial, leading to the widespread but incorrect belief that antibiotics can be used against viruses. Some sources distinguish between antibacterial and antibiotic; antibacterials used in soaps and cleaners etc., but not as medicine. This article treats the terms as synonymous and according to the most widespread definition of antibiotics being a substance used against bacteria.

Medical uses

Antibiotics are mainly used for the treatment or prevention of bacterial infections. They are administered for the treatment of infection as part of an empirical therapy or definitive therapy.

In empirical therapy, a patient has proven or suspected infection, but the responsible microorganism is not yet identified. While the microorganism is being identified the doctor will usually administer the best choice of antibiotic that will be most active against the likely cause of infection usually a broad spectrum antibiotic based on clinical presentation. Empirical therapy is usually initiated before the doctor knows the exact identification of microorgansim causing the infection as the identification process may take several days in the laboratory.

Once the microorganism is identified definitive antibiotic therapy can commence. While the microorganism was being identified the most effective antibiotics against that microorganism were also identified. One of these antibiotics are then used for definitive antibiotic therapy usually a narrow spectrum antibiotic. Identification is a critically important, because it can reduce cost and toxicity of antibiotic therapy and also prevent the emergence of antimicrobial resistance in the community.

Antibiotics may be given prophylactically to prevent infection. Use of prophylactic therapy should be limited high risk populations at risk of developing infection due to weakened immune systems. At risk populations may include patients on immuno-suppressive therapy, patients with cancer or who are having surgery.

• Treatment
  • Bacterial infection
  • Protozoan infection, e.g., metronidazole and Bactrim is effective against several parasitics
  • Immunomodulation, e.g., tetracycline, which is effective in periodontal inflammation, and dapsone, which is effective in autoimmune diseases such as oral mucous membrane pemphigoid
  • Nonoperative resource for patients who have non-complicated acute appendicitis. Treatment with antibiotics has been reported to work, with almost no cases of remission.
• Prevention of infection
  • Surgical wound
  • Dental antibiotic prophylaxis
  • Conditions of neutropenia, e.g. cancer-related
  • Persons with reduced immune system function, e.g., those infected with HIV, who often are prescribed Bactrim for prophylaxis to pneumonia

Administration

Oral antibiotics are taken by mouth, whereas parenteral administration of antibiotics (either intravenously or by injection) may be used in more serious cases of infection, such as for deep-seated systemic infections. Oral therapy is recommended for patients with mild to moderate infection with normal gastrointestinal function or upon becoming clinically stable after parenteral therapy. Antibiotics may also sometimes be administered topically, at the site of infection, as with eye drops or ointments. Advantages of local application of antibiotic at the site of infection include achieving high and sustained concentration of antibiotic at the site of infection, reducing the potential for systemic absorption and toxicity, total volumes of antibiotic required to treat the infection are reduced, and, possibly, limiting potential for the development of antibiotic resistance. However, some systemic absorption of antibiotic may occur and quantity of antibiotic applied is difficult to accurately dose, as well as the fact that local hypersensitivity or contact dermatitis reactions may occur.

The topical antibiotics are:

• erythromycin
• clindamycin
• gentamycin
• tetracycline
• meclocycline
• sulfacetamide

Topical medications that act as comedolytics as well as antibiotics are:

• benzoyl peroxide
• azelaic acid

Side-effects

Health advocacy messages such as this one encourage patients to talk with their doctor about safety in using antibiotics.

Antibiotics are screened for any negative effects on humans or other mammals before approval for clinical use, and are usually considered safe and most are well tolerated. However, some antibiotics have been associated with a range of adverse side effects. Side-effects range from mild to very serious depending on the antibiotics used, the microbial organisms targeted, and the individual patient. Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity reactions or anaphylaxis. Safety profiles of newer drugs are often not as well established as for those that have a long history of use. Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis. Common side-effects include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridium difficile. 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 elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.

Occasionally, antibiotics are prescribed for specific side effects, such as the prokinetic effect of erythromycin on the gut.

Possible Health Risks

Obesity

Exposure to antibiotics early in life is associated with increased body mass in humans and mouse models. Early life is a critical period for the establishment of the intestinal microbiota and for metabolic development. Mice exposed to subtherapeutic antibiotic treatment (STAT)– with either penicillin, vancomycin, or chlortetracycline had altered composition of the gut microbiota as well as its metabolic capabilities. One study has reported that mice given low-dose penicillin (1 μg/g body weight) around birth and throughout the weaning process had an increased body mass and fat mass, accelerated growth, and increased hepatic expression of genes involved in adipogenesis, compared to control mice. In addition, penicillin in combination with a high-fat diet increased fasting insulin levels in mice. However, it is unclear whether or not antibiotics cause obesity in humans. Studies have found a correlation between early exposure of antibiotics (<6 months) and increased body mass (at 10 and 20 months). Another study found that the type of antibiotic exposure was also significant with the highest risk of being overweight in those given macrolides compared to penicillin and cephalosporin. Therefore, there is correlation between antibiotic exposure in early life and obesity in humans, but whether or not there is a causal relationship remains unclear. Although there is a correlation between antibiotic use in early life and obesity, the effect of antibiotics on obesity in humans needs to be weighed against the beneficial effects of clinically indicated treatment with antibiotics in infancy.

Drug-drug interactions

Birth control pills

The majority of studies indicate antibiotics do interfere with contraceptive pills, such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). In cases where antibacterials have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibacterial 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 antibacterials that are suspected to interact with oral contraceptives.

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. Despite the lack of a categorical counterindication, the belief that alcohol and antibiotics should never be mixed is widespread.

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

Main article: Antimicrobial 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. A 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.

Antibiotics antagonism

Chloramphenicol and tetracyclines are antagonists to penicillins and aminoglycosides. This means the combined effect of two antibiotics from separate groups can be less than a single antibiotic. However, this can vary depending on the species of bacteria.

Classes

Main article: List of antibiotics

Molecular targets of antibiotics on the bacteria cell

Antibacterial 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. Those that target protein synthesis (macrolides, lincosamides and tetracyclines) are usually bacteriostatic (with the exception of bactericidal aminoglycosides). Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes of antibacterial compounds, four new classes of antibacterial antibiotics have been brought into 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

Main article: Production of antibiotics

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 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

Main article: Antibiotic resistance

Scanning electron micrograph of a human neutrophil ingesting methicillin-resistant Staphylococcus aureus (MRSA)

The emergence of resistance of bacteria to antibiotics is a common phenomenon. 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 biodegredation 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.

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 (TB) 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 May 26, 2016 an E coli bacteria "superbug" was identified in the United States resistant to colistin, "the last line of defence" antibiotic.

Misuse

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

Main article: Antibiotic misuse

Per the The ICU Book "The first rule of antibiotics is 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. Self prescription 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.

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 (NIH), as well as other US agencies. An NGO 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 EU has banned the use of antibiotics as growth-promotional agents since 2003. Moreover, several organizations (including the World Health Organization, the U.S. National Academy of Science, 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 (APHA).

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.

History

See also: Timeline of antibiotics

Penicillin, the first natural antibiotic discovered by Alexander Fleming in 1928

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 2000 years ago. Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections. More recent observations made in the laboratory of antibiosis between microorganisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics". 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 1942. 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 color 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 salvarsan now called arsphenamine.

The effects of some types of mold on infection had been noticed many times over the course of history (see: History of penicillin). In 1928, Alexander Fleming noticed the same effect in a Petri dish, where a number of disease-causing bacteria were killed by a fungus of the genus Penicillium. Fleming postulated that the effect is mediated by an antibacterial compound he named penicillin, and that its antibacterial properties could be exploited for chemotherapy. He initially characterized 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.

Alexander Fleming

The first sulfonamide and first commercially available antibacterial, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 at the Bayer Laboratories of the IG Farben conglomerate in Germany. Domagk received the 1939 Nobel Prize for Medicine for his efforts. 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.

In 1939, coinciding with the start of World War II, Rene Dubos reported the discovery of the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and 80% tyrocidine, from B. brevis. It was one of the first commercially manufactured antibiotics universally 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 the war.

Florey and Chain 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 determined 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. The discovery of such a powerful antibiotic was unprecedented, and 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, Ernst Chain and Howard Florey shared the 1945 Nobel Prize in Medicine with Fleming. Florey credited 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.

Etymology

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 ones to be discovered were rod-shaped.

Research

Alternatives

The increase in bacterial strains that are resistant to conventional antibacterial therapies has prompted the development of bacterial disease treatment strategies that are alternatives to conventional antibacterials, including phage therapy.

Resistance-modifying agents

One strategy to address bacterial drug resistance is the discovery and application of compounds that modify resistance to common antibacterials. For example, some resistance-modifying agents may inhibit multidrug resistance mechanisms, such as drug efflux from the cell, thus increasing the susceptibility of bacteria to an antibacterial. Targets include:

• The efflux inhibitor Phe-Arg-β-naphthylamide.
• Beta-lactamase inhibitors, such as clavulanic acid and sulbactam.

Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic-tolerant bacteria by keeping their metabolism active.

Vaccines

Vaccines rely on immune modulation or augmentation. 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. Vaccines made from attenuated whole cells or lysates have been replaced largely by less reactogenic, cell-free vaccines consisting of purified components, including capsular polysaccharides and their conjugates, to protein carriers, as well as inactivated toxins (toxoids) and proteins.

Phage therapy

Phage therapy is another method for treating antibiotic-resistant strains of bacteria. Phage therapy infects pathogenic bacteria with their own viruses, bacteriophages. Bacteriophages, also known simply as phages, infect and can kill bacteria. 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 able to infect and destroy further bacteria of the same strain. The high specificity of phage protects "good" bacteria from destruction. When applicable, bacteriophage therapy defeats antibiotic resistant bacteria.

Supplements

Some over-the-counter antioxidant supplements containing polyphenols, such as grape seed extract, demonstrate in vitro anti-bacterial properties.

Development of new antibiotics

In April 2013, the Infectious Disease Society of America (IDSA) reported that the weak antibiotic pipeline does not match bacteria's increasing ability to develop resistance. Since 2009, only 2 new antibiotics were approved in the United States. The number of new antibiotics approved for marketing per year declines continuously. The report identified seven antibiotics against the Gram-negative bacilli (GNB) currently in phase 2 or phase 3 clinical trials. However, these drugs do not address the entire spectrum of resistance of GNB. Some of these antibiotics are combination of existent treatments:

• Ceftolozane/tazobactam (CXA-201; CXA-101/tazobactam): Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor). FDA approved on 12/19/2014.
• Ceftazidime/avibactam (ceftazidime/NXL104): Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 3.
• Ceftaroline/avibactam (CPT-avibactam; ceftaroline/NXL104): Anti-MRSA cephalosporin/ β-lactamase inhibitor combination (cell wall synthesis inhibitor)
• Imipenem/MK-7655: Carbapenem/ β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 2.
• Plazomicin (ACHN-490): Aminoglycoside (protein synthesis inhibitor). In phase 2.
• Eravacycline (TP-434): Synthetic tetracycline derivative / protein synthesis inhibitor targeting the ribosome. Development by Tetraphase, Phase 2 trials complete.
• Brilacidin (PMX-30063): Peptide defense protein mimetic (cell membrane disruption). In phase 2.

Streptomyces research is expected to provide new antibiotics, including treatment against MRSA and infections resistant to commonly used medication. Efforts of John Innes Centre and universities in the UK, supported by BBSRC, resulted in the creation of spin-out companies, for example Novacta Biosystems, which has designed the type-b lantibiotic-based compound NVB302 (in phase 1) to treat Clostridium difficile infections.

Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor. Antibiotic Development to Advance Patient Treatment (ADAPT) Act aims to fast track the drug development 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."

See also

• Antiviral
• Antifungal
• Antiprotozoal
• Antimalarial

References

External links

• Antibiotics at DMOZ

UpToDate Contents

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• 1. β-ラクタム系抗生物質：作用機序、耐性および有害作用 beta lactam antibiotics mechanisms of action and resistance and adverse effects
• 2. カテーテル関連血流感染症の治療のための抗菌薬ロック療法 antibiotic lock therapy for treatment of catheter related bloodstream infections
• 3. セフェム系 cephalosporins
• 4. 抗菌薬感受性試験の概要 overview of antibacterial susceptibility testing
• 5. フルオロキノロン系抗菌薬に対する過敏反応 hypersensitivity reactions to fluoroquinolones antimicrobials

English Journal

• Rapid and accurate detection of Escherichia coli growth by fluorescent pH-sensitive organic nanoparticles for high-throughput screening applications.

• Si Y1, Grazon C2, Clavier G2, Rieger J3, Audibert JF2, Sclavi B4, Méallet-Renault R5.
• Biosensors & bioelectronics.Biosens Bioelectron.2016 Jan 15;75:320-7. doi: 10.1016/j.bios.2015.08.028. Epub 2015 Aug 15.
• Rapid detection of bacterial growth is an important issue in the food industry and for medical research. Here we present a novel kind of pH-sensitive fluorescent nanoparticles (FANPs) that can be used for the rapid and accurate real-time detection of Escherichia coli growth. These organic particles
• PMID 26334591

• A novel electrochemical aptasensor based on arch-shape structure of aptamer-complimentary strand conjugate and exonuclease I for sensitive detection of streptomycin.

• Mohammad Danesh N1, Ramezani M2, Sarreshtehdar Emrani A3, Abnous K4, Taghdisi SM5.
• Biosensors & bioelectronics.Biosens Bioelectron.2016 Jan 15;75:123-8. doi: 10.1016/j.bios.2015.08.017. Epub 2015 Aug 11.
• Detection and quantitation of antibiotic residues in blood serum and animal foodstuffs are of great significance. In this study, an electrochemical aptasensor was developed for sensitive and selective detection of streptomycin, based on exonuclease I (Exo I), complimentary strand of aptamer (CS), Ar
• PMID 26302000

• Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells.

• Qiu XH1, Shao JJ, Mei JG, Li HQ, Cao HQ.
• Acta haematologica.Acta Haematol.2016;135(2):103-9. doi: 10.1159/000438855. Epub 2015 Oct 28.
• Clarithromycin (CAM) is a macrolide antibiotic that is widely used in the treatment of respiratory tract infections, sexually transmitted diseases and infections caused by the Helicobacter pylori and Mycobacterium avium complex. Recent studies showed that CAM was highly effective against multiple my
• PMID 26505646

• Rapid Detection of Pseudomonas aeruginosa and Acinetobacter baumannii Harboring bla(VIM-2), bla(IMP-1) and bla(OXA-23) Genes by Using Loop-Mediated Isothermal Amplification Methods.

• Kim HJ1, Kim HS2, Lee JM1,3, Yoon SS3,4, Yong D5.
• Annals of laboratory medicine.Ann Lab Med.2016 Jan;36(1):15-22. doi: 10.3343/alm.2016.36.1.15.
• BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB) are the leading causes of nosocomial infections. A rapid and sensitive test to detect CRPA and CRAB is required for appropriate antibiotic treatment. We optimized a loop-mediated isothermal amplificatio
• PMID 26522754

Japanese Journal

• Yoton Joho rensai 2015 海外豚情報 ア・ラ・カルト 抗菌剤とその重要性

• 岡野 圭介
• 月刊養豚情報 43(2), 52-54, 2015-02
• NAID 40020343467

• 研究・症例 感染性肺囊胞4例の治療経験

• 松毛 真一,川原 洋一郎,田尾 嘉浩 [他]
• 日本胸部臨床 74(1), 73-78, 2015-01
• NAID 40020316902

• Crystal Structure of IMP-2 Metallo-β-lactamase from Acinetobacter spp. : Comparison of Active-Site Loop Structures between IMP-1 and IMP-2

• Yamaguchi Yoshihiro,Matsueda Satoshi,Matsunaga Kazuyo [他]
• Biological & pharmaceutical bulletin 38(1), 96-101, 2015-01
• NAID 40020311908

• カテーテル関連血流感染に対する抗菌薬適正使用がその後の菌血症再発に及ぼす影響

• 西 圭史,中村 貴枝子,高橋 陽子 [他]
• 日本環境感染学会誌 = Japanese journal of environmental infecions 30(1), 7-13, 2015
• NAID 40020336581

Related Links

• 抗菌薬インターネットブック

抗菌薬の検索サイト ANTIBIOTIC-BOOKS 抗菌薬インターネットブック 抗菌薬インターネットブックは、抗細菌剤を中心に、抗結核剤・抗真菌剤・抗ウィルス剤・抗原虫剤まで、約120の薬剤を収載した、抗菌薬の検索サイトです。 検索方法は ...

• Antibiotic | Define Antibiotic at Dictionary.com

Antibiotic definition, any of a large group of chemical substances, as penicillin or streptomycin, produced by various microorganisms and fungi, having the capacity in dilute solutions to inhibit the growth of or to destroy bacteria and ...

• Antibiotics

Antibiotics

Related Pictures

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★リンクテーブル★

リンク元	「antibacterial」「antimicrobial agent」「antimicrobial」「抗菌剤」「anti-bacterial agent」
拡張検索	「beta-lactam antibiotic」「Streptomyces antibioticus」「combination antibiotic therapy」「penicillin antibiotics」

「antibacterial」

　　[★]

• adj.

• 抗菌性の、抗菌的な、抗菌の

• n.

• 抗菌薬

関

anti-bacterial agent、antibacterial agent、antibacterial drug、antibacterially、antibacterials、antibiotic、antibiotics、antimicrobial、antimicrobial agent、antimicrobials

　 　

「antimicrobial agent」

　　[★]

• 抗菌薬、抗菌剤

関

anti-bacterial agent、anti-infective agent、antibacterial、antibacterial agent、antibacterial drug、antibacterials、antibiotic、antibiotics、antiinfective agent、antimicrobial、antimicrobials、microbicide

「antimicrobial」

　　[★]

• adj.

• 抗菌の

• n.

• 抗菌薬、抗菌剤

関

anti-bacterial agent、antibacterial、antibacterial agent、antibacterial drug、antibacterials、antibiotic、antibiotics、antimicrobial agent、antimicrobials

　

「抗菌剤」

　　[★]

英

antimicrobial agent、antibacterial agent、antibacterial drug、antibiotic、antimicrobial

関

抗菌、抗菌性、抗菌薬、抗生剤、抗生物質、殺菌剤、抗感染薬、抗細菌薬

「anti-bacterial agent」

　　[★]

• 抗菌薬、抗細菌薬

関

antibacterial、antibacterial agent、antibacterial drug、antibacterials、antibiotic、antibiotics、antimicrobial、antimicrobial agent、antimicrobials、bacteriocide

「beta-lactam antibiotic」

　　[★]

• βラクタム系抗生物質、βラクタム系抗菌薬、βラクタム抗生物質、βラクタム剤

関

beta-lactam

「Streptomyces antibioticus」

　　[★]

ストレプトマイセス・アンチビオチクス、ストレプトミセス・アンチビオチクス

「combination antibiotic therapy」

　　[★]

• 抗菌薬併用療法、抗生物質併用療法

「penicillin antibiotics」

　　[★] ペニシリン系抗菌薬