n.

抗生物質

WordNet

any drug that destroys bacteria or inhibits their growth (同)antibacterial_drug, bactericide
destroying bacteria or inhibiting their growth
capable of destroying or inhibiting the growth of disease-causing microorganisms (同)antimicrobic
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
of or relating to antibiotic drugs

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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）』「2016/08/31 17:04:58」(JST)

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培地上での実験。抗生物質を含むディスクの周囲では、黄色ブドウ球菌の繁殖が抑制される。菌が繁殖していない円形の部分を阻止円と呼ぶ。

抗生物質（こうせいぶっしつ、英語: antibiotics）とは、微生物が産生し、ほかの微生物など生体細胞の増殖や機能を阻害する物質の総称^[1]。一般に「抗菌薬（英語: antibacterial drugs）」と同義であるが、広義には抗ウイルス剤や抗真菌剤、抗がん剤も含む。

アレクサンダー・フレミングが1928年にアオカビから見付けたペニシリンが世界初の抗生物質である。

1990年頃には、天然由来の抗生物質は5,000～6,000種類があると言われ、約70種類（微量成分を含めると約100種類）が実用に使われている。この他にも半合成抗生物質も80種が利用されている^[1]。

名称と定義

antibioticsの単語は、抗生物質の一種ストレプトマイシンを発見したセルマン・ワクスマンが1942年のアメリカ細菌学会で、二種の細菌が同じ場所に存在する際に生じる拮抗する現象（英語: antibiosis）を元に決められた。そのため、当初の抗生物質の定義は「微生物由来の、他の微生物の発育や代謝を阻害する化学物質」であった^[1]。

1928年のペニシリンの発見以来、感染症に対する多くの「抗生物質」は細菌に対する「抗菌薬 (antibacterial drugs)」がほとんどであり、「抗生物質 (antibiotics)」と言えば「抗菌薬 (antibacterial drugs)」のことを指すことが一般だった。

その後探査と研究が進み、細菌以外の感染症が多く知られるようになり、ウイルスや真菌等の感染症に対する抗生物質が次々と開発され、抗ウイルス薬や抗真菌薬が出現し、また天然物を化学的に修飾して改良したり、天然ではなく人工合成の抗菌薬も開発されていった。やがて抗腫瘍物質を概念に含めるため、冒頭のような定義に拡大された^[1]。

1953年に国立予防衛生研究所（現：国立感染症研究所）の梅澤濱夫博士が発見したザルコマイシンは、細菌・真菌への抗微生物活性のみならず、抗腫瘍性活性を持つ抗生物質であった。北里研究所の秦藤樹博士によるマイトマイシンC、イタリアのFederico Arcamone博士のアドリアマイシン（現：ドキソルビシン）も抗腫瘍性抗生物質として実用化された。

言い換えると、抗生物質とは「微生物の産生物に由来する抗菌薬、抗真菌薬、抗ウイルス薬、そして抗がん剤であり、その大半が抗菌薬」である。現在、感染症を専門とする研究機関・医療機関では「抗生物質」という名称はあまり用いられず、それぞれ「抗菌薬」・「抗ウイルス薬」・「抗真菌薬」・「抗寄生虫薬」と言う名称を用いる。

近年では化学合成で生産されるものや、天然の誘導体から半合成されるものもある^[1]。ピリドンカルボン酸系（キノロン系、ニューキノロン系）やサルファ剤など、完全に人工的に合成された抗菌性物質も、一般的に｢抗生物質｣と呼ばれることが多いが、厳密には｢合成抗菌薬｣と呼ぶのが正しい。抗菌性の抗生物質、合成抗菌薬をあわせて、広義の抗菌薬と呼ぶ。

さらに、生命活動に深く関与する酵素の活動を選択的に阻む物質、高等動物の免疫系で活躍する物質なども含めた再定義が求められている^[1]。

分類

抗生物質の分類は、化学構造からの分類と作用による分類の2つがある^[1]。

化学構造からの分類では、β-ラクタム系、アミノグリコシド系、マクロライド系、テトラサイクリン系、ペプチド系、核酸系、ポリエン系などに大別されるが、さらに細かくペニシリン系、セフェム系、モノバクタム系を加える場合もある^[1]。

作用からの分類では、抗細菌性、抗カビ（真菌）性、抗ウイルス性、抗腫瘍性などに分けられる。用途を重視する場合は、医療用、動物用、農業用などで分類される。作用域から、広範囲・狭域で区分される事もある^[1]。作用機序から、細胞壁作用性などの呼称もある^[1]。

作用機序の分類としては、核酸合成阻害薬、細胞壁合成阻害薬、蛋白合成阻害薬に大きく分けられる。

核酸合成阻害薬: リファンピシン
細胞壁合成阻害薬: βラクタム系、ホスホマイシン、バンコマイシン
蛋白合成阻害薬: テトラサイクリン系、マクロライド系、アミノグリコシド系、クロラムフェニコール

キノロン系やサルファ剤は核酸合成阻害を機序とした合成抗菌薬であり、抗生物質ではない。

薬理

抗生物質を含む抗菌剤は、細菌が増殖するのに必要な代謝経路に作用することで細菌にのみ選択的に毒性を示す化学物質である。例えば、β-ラクタム系抗生物質は細菌特有の細胞壁の合成を阻害するが、人体の細胞に対してはほとんど毒性を示さない。アルコール、ポビドンヨードなどのように、単に化学的な作用で細菌を死滅させる殺菌剤、消毒薬とは区別される。

人類の最大の脅威であった細菌感染を克服し、平均寿命を大幅に伸ばすこととなった^[2]。しかし、感染症との戦いは終わったわけではなく、治療法の開発されていない新興感染症、抗生物質の効力が薄くなるなどした再興感染症などが問題となっている。

また、抗生物質は病原性を示していない細菌にも作用するため、多量に使用すると体内の常在菌のバランスを崩してしまう場合がある。それにより常在菌が極端に減少すると、他の細菌や真菌（カビ）などが爆発的に繁殖し、病原性を示す場合もある。さらに、生き残った菌が耐性化する耐性菌の出現も問題となっている。

臨床応用

細菌に対する薬物療法については「化学療法 (細菌)」を参照

悪性腫瘍に対する薬物療法については「抗がん剤」を参照

自己免疫疾患・移植医療に対する薬物療法については「免疫抑制剤」を参照

抗生物質の大部分は抗菌薬として使用される。抗菌薬の投与方法は臨床薬理学の考え方が適用されている。細菌感染症に対する抗生物質の投与は、抗生物質は化学療法剤とは異なるものの、臨床医学的にはまとめて化学療法と呼ばれている。

その他、ポリエンマクロライド系抗生物質は真菌の治療に使用される。また、癌治療にはマイトマイシンCやブレオマイシン、アドリアマイシン、ドキソルビシンなどの抗生物質が使用される。またシクロスポリン、タクロリムス、エベロリムスも抗生物質であり、免疫抑制剤として膠原病、自己免疫疾患、移植医療の現場で活躍している。

耐性と乱用

米国CDCの"Get Smart"キャンペーンポスター。抗生物質は風邪などの感染症に効かないことを警告している。

詳細は「:en:Antibiotic misuse」を参照

The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them.^[3]
（抗生物質の第一のルールは使わないようにすること、第二のルールは使う種類を多くしすぎないようにすることである）

—Paul L. Marino、The ICU Book

耐性菌問題に関する組織は、不必要な抗生物質の使用を削減するキャンペーンを行っている^[4]。抗生物質の誤用と乱用問題の対応のため、米国では省庁横断の耐性菌タスクフォースが作られた。タスクフォースは耐性菌の問題を主眼としており、アメリカ疾病予防管理センター (CDC)、アメリカ食品医薬品局 (FDA)、アメリカ国立衛生研究所 (NIH)、などの機関が参加している^[5]。また、Keep Antibiotics WorkingといったNGOも存在する^[6]。フランスでは、2002年に政府による “Antibiotics are not automatic” キャンペーンが開始され、不必要な抗生物質の処方を削減をめざしており、とりわけ子供に重点を置いている^[7]。

脚注

[ヘルプ]

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j 生化学辞典第2版、p.471【抗生物質】
^ McKeown. T. (1979). The role of medicine. Oxford, Basil Blackwell.
^ Marino PL (2007). “Antimicrobial therapy”. The ICU book. Hagerstown, MD: Lippincott Williams & Wilkins. p. 817. ISBN 978-0-7817-4802-5.
^ Larson E (2007). “Community factors in the development of antibiotic resistance.”. Annu Rev Public Health 28: 435–447. doi:10.1146/annurev.publhealth.28.021406.144020. PMID 17094768.
^ CDC - Antibiotic / Antimicrobial Resistance (Report). アメリカ疾病予防管理センター. (2009-03-12).
^ “Keep Antibiotics Working”. Keep Antibiotics Working. 2010年11月17日時点のオリジナルよりアーカイブ。2010年5月21日閲覧。
^ Sabuncu E, David J, Bernède-Bauduin C et al. (2009). Klugman, Keith P.. ed. “Significant reduction of antibiotic use in the community after a nationwide campaign in France, 2002–2007”. PLoS Med 6 (6): e1000084. doi:10.1371/journal.pmed.1000084. PMC 2683932. PMID 19492093. オリジナルの2010-11-17時点によるアーカイブ。.

参考文献

抗菌薬の考え方、使い方　中外医学社　ISBN 4498017587
『生化学辞典第2版』東京化学同人、1995年、第2版第6刷。ISBN 4-8079-0340-3。

外部リンク

ウィキメディア・コモンズには、抗生物質に関連するカテゴリがあります。

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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^[1] drug used in the treatment and prevention of bacterial infections.^[2]^[3] They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity.^[4]^[5] Antibiotics are not effective against viruses such as the common cold or influenza, and their inappropriate use allows the emergence of resistant organisms.^[2] 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 a little green mold (Penicillium chrysogenum), in one of his culture plates. He observed that the presence of the mold killed or prevented the growth of the bacteria.^[6]

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,^[7]^[8]^[9] 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".^[10]

The era of antibacterial treatment began with the discovery of arsphenamine, first synthesized by Alfred Bertheim and Paul Ehrlich in 1907, and used to treat syphilis.^[11]^[12] The first systemically active antibacterial drug, prontosil was discovered in 1933 by Gerhard Domagk,^[12]^[13] for which he was awarded the 1939 Nobel Prize.^[14] All classes of antibiotics in use today were first discovered prior to the mid 1980s.^[15]

Sometimes the term antibiotic is used to refer to any substance used against microbes,^[16] synonymous with antimicrobial,^[17] leading to the widespread but incorrect belief that antibiotics can be used against viruses.^[18] Some sources distinguish between antibacterial and antibiotic; antibacterials are used in soaps and cleaners generally and antibiotics are used as medicine.^[19]

1 Medical uses
- 1.1 Administration
2 Side-effects
- 2.1 Obesity
3 Interactions
- 3.1 Birth control pills
- 3.2 Alcohol
4 Pharmacodynamics
- 4.1 Combination therapy
5 Classes
6 Production
7 Resistance
- 7.1 Misuse
8 History
- 8.1 Etymology
9 Research
- 9.1 Alternatives
- 9.2 Resistance-modifying agents
- 9.3 Vaccines
- 9.4 Phage therapy
- 9.5 Supplements
- 9.6 Development of new antibiotics
10 See also
11 References
12 Further reading
13 External links

Medical uses

Antibiotics are used to treat or prevent bacterial infections,^[20] and sometimes protozoan infections. (Metronidazole is effective against a number of parasitic diseases). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an empiric therapy is adopted.^[21] This involves the administration of a broad-spectrum antibiotic based on the signs and symptoms presented and is initiated pending laboratory results that can take several days.^[20]^[21]

When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance.^[21] To avoid surgery antibiotics may be given for non-complicated acute appendicitis. Effective treatment has been evidenced.^[22]

Antibiotics may be given as a preventive measure (prophylactic) and this is usually limited to at-risk populations such as those with a weakened immune system (particularly in HIV cases to prevent pneumonia), those taking immunosuppressive drugs, cancer patients and those having surgery.^[20] Their use in surgical procedures is to help prevent infection of incisions made. They have an important role in dental antibiotic prophylaxis where their use may prevent bacteremia and consequent infective endocarditis. Antibiotics are also used to prevent infection in cases of neutropenia particularly cancer-related.^[23]^[24]

Administration

There are different routes of administration for antibiotic treatment. Antibiotics are usually taken by mouth. In more severe cases, particularly deep-seated systemic infections, antibiotics can be given intravenously or by injection.^[2]^[21] Where the site of infection is easily accessed antibiotics may be given topically in the form of eye drops onto the conjuctiva for conjunctivitis or ear drops for ear infections and acute cases of swimmer's ear. Topical use is also one of the treatment options for some skin conditions including acne and cellulitis.^[25] Advantages of topical application include achieving high and sustained concentration of antibiotic at the site of infection; reducing the potential for systemic absorption and toxicity, and total volumes of antibiotic required are reduced, thereby also reducing the risk of antibiotic misuse.^[26] However, some systemic absorption of the antibiotic may occur; the quantity of antibiotic applied is difficult to accurately dose, and there is also the possibility of local hypersensitivity reactions or contact dermatitis occurring.^[26]

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 before their approval for clinical use, and are usually considered safe and well tolerated. However, some antibiotics have been associated with a wide range of adverse side effects^[27] from mild to very severe depending on the type of antibiotic used, the microbes targeted, and the individual patient.^[28] Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity or allergic reactions.^[5] Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis.^[29] Safety profiles of newer drugs are often not as well established as for those that have a long history of use.^[27]

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.^[30] Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area.^[31] Additional side-effects can result from interaction with other drugs, such as the possibility of tendon damage from the administration of a quinolone antibiotic with a systemic corticosteroid.^[32]

Obesity

Exposure to antibiotics early in life is associated with increased body mass in humans and mouse models.^[33] Early life is a critical period for the establishment of the intestinal microbiota and for metabolic development.^[34] 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.^[35] 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.^[36] In addition, penicillin in combination with a high-fat diet increased fasting insulin levels in mice.^[36] 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).^[37] 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.^[38] 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.^[34]

Interactions

Birth control pills

The majority of studies indicate antibiotics do interfere with birth control pills,^[39] such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%).^[40] In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic rifampicin, these cases may be due to an increase in the activities of hepatic liver enzymes' causing increased breakdown of the pill's active ingredients.^[39] 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.^[41]^[42] Clinicians have recommended that extra contraceptive measures be applied during therapies using antiiotics that are suspected to interact with oral contraceptives.^[39]

Alcohol

Interactions between alcohol and certain antibiotics may occur and may cause side-effects and decreased effectiveness of antibiotic therapy.^[43]^[44] 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.^[45] Therefore, potential risks of side-effects and effectiveness depend on the type of antibiotic administered.^[46]

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.^[45] In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption.^[47] Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.^[48]

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.^[49] A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.^[50] These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection.^[49]^[51] Since the activity of antibacterials depends frequently on its concentration,^[52] in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial.^[49]^[53] 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.^[54]

Combination therapy

In important infectious diseases, including tuberculosis, combination therapy (i.e., the concurrent application of two or more antibiotics) has been used to dely or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their synergistic effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect.^[55]^[56] Methicillin-resistant Staphylococcus aureus infections may be treated with a combination therapy of fusidic acid and rifampin.^[55] Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if the individual antibiotic was given as part of a monotherapy.^[55] For example, Chloramphenicol and tetracyclines are antagonists to penicillins and aminoglycosides. However, this can vary depending on the species of bacteria.^[57] In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic.^[55]^[56]

Classes

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 target bacterial functions or growth processes.^[58] 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).^[59] Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as gram-negative or gram-positive, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year break in discovering new classes of antibacterial compounds, four new classes of 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).^[60]^[61]

Production

With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds.^[62] 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.^[62] Many antibacterial compounds are relatively small molecules with a molecular weight of less than 1000 daltons.^[63]

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.^[64]

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.^[65] For example, antibacterial selection for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment.^[66] 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.^[67]

Resistance may take the form of biodegredation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces.^[68] The survival of bacteria often results from an inheritable resistance,^[69] 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.^[70]

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.^[71]

Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms.^[72] Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability.^[73]

Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains.^[74] 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.^[74] Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains.^[75]^[76] The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange.^[69] For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes.^[69]^[77] Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials.^[77] 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.^[77]

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.^[78] For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials.^[79] 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."^[80] On May 26, 2016 an E coli bacteria "superbug" was identified in the United States resistant to colistin, "the last line of defence" antibiotic.^[81]^[82]

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.

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."^[83] 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.^[84] 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.^[27]^[84] The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s.^[67]^[85] 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.^[85]

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".^[86] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.^[87]^[88]

Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics.^[84] 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.^[89] An NGO campaign group is Keep Antibiotics Working.^[90] 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.^[91]

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.^[92] Moreover, several organizations (including the World Health Organization, the National Academy of Sciences, and the U.S. Food and Drug Administration) have advocated restricting the amount of antibiotic use in food animal production.^[93] 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^[94] and H.R. 2562^[95]) aimed at phasing out nontherapeutic use of antibiotics in US food animals were proposed, but have not passed.^[94]^[95] 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).^[96]

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.^[97]

History

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.^[98] Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections.^[99]^[100] 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".^[101] 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.^[58]^[102]^[103] 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.^[102]^[104] These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942.^[58]^[102]^[105] Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s.^[58] 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^[58]^[106]^[107] 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.^[108]^[109]

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.^[107] 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.^[110]^[111]

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.^[112] Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also proved too toxic for systemic usage. Research results obtained during that period were not shared between the Axis and the Allied powers during world war II and limited access during the cold war.^[113]

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.^[114] 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.^[112]

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.^[102]^[105] 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.^[115]^[116]

The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for life, lively",^[117] which comes from βίωσις (biōsis), "way of life",^[118] and that from βίος (bios), "life".^[48]^[119] The term "antibacterial" derives from Greek ἀντί (anti), "against"^[120] + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane",^[121] because the first ones to be discovered were rod-shaped.^[122]

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.^[123]

Resistance-modifying agents

One strategy to address bacterial drug resistance is the discovery and application of compounds that modify resistance to common antibacterials. Resistance modifying agents are capable of partly or completely suppressing bacterial resistance mechanisms.^[124] 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.^[124]^[125] Targets include:

The efflux inhibitor Phe-Arg-β-naphthylamide.^[125]
Beta-lactamase inhibitors, such as clavulanic acid and sulbactam^[126]

Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic-tolerant bacteria by keeping their metabolism active.^[127]

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.^[128] 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.^[129]

Phage therapy

Phage injecting its genome into bacterial cell

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.^[130] 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.^[130] The high specificity of phage protects "good" bacteria from destruction. When applicable, bacteriophage therapy defeats antibiotic resistant bacteria.^[130]

Supplements

Some antioxidant dietary supplements contain polyphenols, such as grape seed extract, and demonstrate in vitro anti-bacterial properties.^[131]^[132]^[133]

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.^[134]^[135] Some of these antibiotics are combination of existent treatments:

Tazobactam

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.^[136]
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.^[137]^[138] Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor.^[135] In the US, the Antibiotic Development to Advance Patient Treatment (ADAPT) Act was introduced with the aim of fast tracking the drug development of antibiotics to combat the growing threat of 'superbugs'. Under this Act, FDA can approve antibiotics and antifungals treating life-threatening infections based on smaller clinical trials. The CDC will monitor the use of antibiotics and the emerging resistance, and publish the data. The FDA antibiotics labeling process, 'Susceptibility Test Interpretive Criteria for Microbial Organisms' or 'breakpoints', will provide accurate data to healthcare professionals.^[139]^[140] 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."^[141]

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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. セフェム系 cephalosporins
3. 抗菌薬感受性試験の概要 overview of antibacterial susceptibility testing
4. 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
5. 成人における市中肺炎の治療に関する抗菌薬の研究 antibiotic studies for the treatment of community acquired pneumonia in adults

English Journal

Validation of a liquid chromatography-electrospray ionization tandem mass spectrometric method to determine six polyether ionophores in raw, UHT, pasteurized and powdered milk.

Pereira MU1, Spisso BF2, Jacob Sdo C2, Monteiro MA2, Ferreira RG2, Carlos Bde S2, da Nóbrega AW2.
Food chemistry.Food Chem.2016 Apr 1;196:130-7. doi: 10.1016/j.foodchem.2015.09.011. Epub 2015 Sep 8.
This study aimed to validate a method developed for the determination of six antibiotics from the polyether ionophore class (lasalocid, maduramicin, monensin, narasin, salinomycin and semduramicin) at residue levels in raw, UHT, pasteurized and powdered milk using QuEChERS extraction and high perfor
PMID 26593474

In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy.

Di Giulio M1, Di Campli E1, Di Bartolomeo S1, Cataldi V1, Marzio L2, Grossi L2, Ciccaglione AF2, Nostro A3, Cellini L1.
Scandinavian journal of gastroenterology.Scand J Gastroenterol.2016 Mar;51(3):263-9. doi: 10.3109/00365521.2015.1092577. Epub 2015 Oct 7.
OBJECTIVE: Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy.MATERIALS AND M
PMID 26554617

Statistical optimization of cell disruption techniques for releasing intracellular X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis spp. lactis.

Üstün-Aytekin Ö1, Arısoy S2, Aytekin AÖ3, Yıldız E4.
Ultrasonics sonochemistry.Ultrason Sonochem.2016 Mar;29:163-71. doi: 10.1016/j.ultsonch.2015.09.010. Epub 2015 Sep 14.
X-prolyl dipeptidyl aminopeptidase (PepX) is an intracellular enzyme from the Gram-positive bacterium Lactococcus lactis spp. lactis NRRL B-1821, and it has commercial importance. The objective of this study was to compare the effects of several cell disruption methods on the activity of PepX. Stati
PMID 26584994

Japanese Journal

日本感染症医薬品協会奨励賞受賞講演会記録 2014年度受賞講演ボリコナゾールのCYP2C19遺伝子多型解析に基づく至適投与量設計法の確立

松元一明
The Japanese journal of antibiotics
NAID 40020569868

岐阜及び愛知県内で分離された肺炎球菌の各種抗菌薬に対する感受性サーベイランス(2011年~2012年)

舟津桃李,水永真吾,福田淑子 [他]
The Japanese journal of antibiotics
NAID 40020569848

メロぺン特定使用成績調査(発熱性好中球減少症)の結果

脇坂孝治,谷俊輔,石橋和士 [他]
The Japanese journal of antibiotics
NAID 40020569831

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★リンクテーブル★

リンク元	「100Cases 14」「antibacterial」「antimicrobial agent」「antimicrobial」「anti-bacterial agent」
拡張検索	「macrolide antibiotics」「cyclic lipopeptide antibiotics」「penicillin antibiotics」

「100Cases 14」

　　[★]

☆case14　複視

■glossary

diplopia n. 複視

筋力低下、筋無力、筋脱力 muscle weakness, muscular weakness

sunken

vt. sinkのpp.

adj.

沈没した、沈んだ、水中の

沈下した、一段低いところにある

落ち込んだ、くぼんだ

3,4-ジアミノピリジン 3,4-diaminopyridine 3,4-DAP K+チャネル阻害薬;ランバート・イートン筋無力症治療

■症例

43-year-old woman

cheif complaint: diplopia

present history: diplopia and holding her head up ; more marked in the evenings, for the last 3 months. difficulty of chewing. voice has become quieter. weight loss (3kg / 6months). non-smoker. drinks about 15 units/week. no regular medication.

past history: no significant previous medical illnesses.

family history: lives with her husband and three children.

・診察 examination

looks well.

organ systems: normal; cardiovascular, respiratory, and abdominal systems.

muscle power; grossly normal. decrease after testing a movement repetitively.

motor function: normal; tone, coordination, reflexes and sensation.

bilateral ptosis. exacerbated by prolonged upward gaze

eye: normal; pupillary reflexes, eye movements, and funduscopy

■答え

diagnosis: myathenia gravis

differential diagnoses:

CASES

上位and/or下位運動ニューロン motor neurone disease　運動ニューロン疾患：線維束性攣縮。進行例では筋力低下

筋 muscular dystrophy　筋ジストロフィー：ある種の筋肉が選択的に筋力低下する。家族歴がある。

筋 dystrophia myotonica　強直性筋ジストロフィー：咬筋、側頭筋、胸鎖乳突筋の筋萎縮、四肢遠位端の筋萎縮。顔貌が特徴的(前頭部脱毛、無表情、窪んだ頬)。家族歴ある。筋電図が診断に有用(急降下爆撃音)。

筋 polymyositis　多発筋炎：普通は皮疹と関節痛が出現。CKが上昇。筋生検が診断に有用

筋 myopathy　ミオパチー：甲状腺中毒性ミオパチー、甲状腺機能低下症によるミオパチー、クッシング症候群によるミオパチー、アルコール性のミオパチー

神経筋接合部？ non-metastatic associations of malignancy (paraneoplastic syndrome(傍腫瘍性症候群 = 腫瘍随伴症候群)のこと)：胸腺腫の症例の10%に重症筋無力症がみられる。ランバート・イートン筋無力症症候群は小細胞癌と関連がある。

HIM.2674

神経筋接合部 congenital myasthenia syndrome　先天性筋無力症症候群
神経筋接合部 drug-induced myasthenia　薬剤性筋無力症

Treatment with penicillamine (used for scleroderma or rheumatoid arthritis) may result in true autoimmune MG, but the weakness is usually mild, and recovery occurs within weeks or months after discontinuing its use.

　重症筋無力症の誘発：ペニシラミン(強皮症や関節リウマチの治療に用いられる)。

　　mildだし、薬剤の中断で改善する。

Aminoglycoside antibiotics or procainamide can cause exacerbation of weakness in myasthenic patients; very large doses can cause neuromuscular weakness in normal individuals.

　重症筋無力症の悪化：アミドグリコシド系抗菌薬、プロカインアミド

　　MGの患者の筋脱力が悪化する。

神経筋接合部 Lambert-Eaton myasthenic syndrome　ランバート・イートン筋無力症症候群：全身の筋肉が冒されるが、特に下肢の近位筋が冒される。MGと同じように～70%の患者で脳神経所見(眼瞼下垂、複視など)が認められる。MGと違うのは(1)反射が消失・減弱すること、(2)自律神経系の変化(口渇、勃起不全)を生じる、(3)神経刺激検査で漸増(waxing)が見られることである。病因は神経筋接合部のP/Q type calcium channelsに対する抗体の出現であり、85%の患者で見いだされる。治療はMGのように血漿交換や免疫抑制薬が使われる。3,4-DAPやpyridostigmineは症状に対する治療のために用いる。前者は運動神経の終末部でカルシウムチャネルをブロックし活動電位を延長させる。後者はアセチルコリンエステラーゼを阻害してシナプスにおける神経伝達物質の濃度を上げる。
精神疾患 neurasthenia　神経衰弱症：歴史的な用語。器質的な障害を伴わない筋無力症のような脱力を伴う症候群。患者は筋脱力や疲労を訴えてやってくる。筋肉の検査では器質的変化は認めないが"jerky release"あるいは"give-away weakness"が認められる。患者の主訴は反復動作による筋力低下よりむしろ疲労や感情鈍麻である。
内分泌疾患 hyperthyroidism　甲状腺機能亢進症：MGが疑われる患者にはthyroid function testをルーチンにやる。甲状腺機能異常は筋無力症の筋力低下を大きくすることがある。
神経筋接合部 botulism　ボツリヌス症：ボツリヌス毒素はシナプス前膜からの神経伝達物質の開口分泌を妨げる。症状はbulbar weakness (複視、構音障害、嚥下困難)。感覚障害はない。深部腱反射は初期には保たれている。進行すれば反射は見られなくなる。筋脱力は全身性。呼吸困難に陥ることがある。精神状態は正常。自律神経症状(麻痺性イレウス、便秘、urinary retention、瞳孔の散大、瞳孔の反応性低下、口渇)。確定診断は血清中の毒素の検出だけど、見つかることはまれ。神経伝導検査(nerve conduction studies)：compound muscle action potentials (CMAPs)の低下。高頻度の刺激で振幅が増加。治療：intubation for airway protection、呼吸補助、aggressive inpatient supportive care(e.g., nutrition, DVT prophylaxis)。馬の抗毒素を検査結果が帰ってくる前に投与する(？)。
上位運動ニューロン intracranial mass lesions　頭蓋内占拠病変：複視はintracranial mass lesionが外眼筋の神経を圧迫することにより生じる。
筋 progressive external ophthalmoplegia　進行性外眼筋麻痺：外眼筋の筋脱力を伴う。四肢の近位筋の筋力低下やそのほかの全身症状を伴うことがある。ミトコンドリアの異常を有する。

■参考文献

HIM = Harrison's Principles of Internal Medicine 17th Edition

CASES = 100 Cases in Clinical Medicine Second edition

IMD = 内科診断学第2版

「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

「anti-bacterial agent」

　　[★]

抗菌薬、抗細菌薬

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

「macrolide antibiotics」

　　[★] マクロライド系抗生物質、マクロライド系抗菌薬

「cyclic lipopeptide antibiotics」

　　[★] 環状リポペプチド系抗菌薬

「penicillin antibiotics」

　　[★] ペニシリン系抗菌薬

[SeikagakuDic471-3-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j 生化学辞典第2版、p.471【抗生物質】

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v t e Antibiotics social and layman issues

Concepts	Antibacterial Fungicide Antiviral drug Antiparasitic Antimicrobial

Social issues	Timeline of antibiotics Antibiotic resistance Antibiotic misuse Antibiotic use in livestock

Pharmacology	Antimicrobial pharmacodynamics List of antibiotics Production of antibiotics

v t e 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)	Antimicrobials: Antibacterials (Antimycobacterials) Antifungals Antivirals Antiparasitics Antiprotozoals Anthelmintics Ectoparasiticides IVIG 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

v t e 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)

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antibiotics