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An '''antibacterial''' is a medicine that kills or inhibits the growth of bacteria. The term '''antibiotic''', in its original sense, meant a substance produced by one microorganism that suppresses the growth of another, and excluded the synthetic agents; in current clinical use the two words are interchangeable. The category encompasses the natural-product fermentation antibiotics (the [[:Category:Penicillins|penicillins]], the [[:Category:Cephalosporins|cephalosporins]], the [[:Category:Aminoglycosides|aminoglycosides]], the [[:Category:Tetracycline_antibiotics|tetracyclines]], the [[:Category:Macrolide_antibiotics|macrolides]], and several others), the semi-synthetic derivatives that extended their spectrum and stability, and the wholly synthetic classes (the sulfonamides, the [[:Category:Fluoroquinolones|fluoroquinolones]], the [[:Category:Nitroimidazoles|nitroimidazoles]], the [[:Category:Nitrofurans|nitrofurans]], the oxazolidinones).

The clinical era began with a synthetic agent. In 1909 [[wikipedia:Paul Ehrlich|Paul Ehrlich]] and his Japanese collaborator [[wikipedia:Sahachiro Hata|Sahachiro Hata]], working at the Frankfurt Royal Institute for Experimental Therapy, identified compound number 606 in their methodical screen of arsenical dyes against the syphilis spirochete; arsphenamine (Salvarsan) was the first medicine of any kind shown to cure a specific bacterial infection, and the prototype of what Ehrlich called the [[wikipedia:Magic bullet (medicine)|''magic bullet'']].<ref name="ehrlich1910">Ehrlich P, Hata S. ''Die experimentelle Chemotherapie der Spirillosen''. Berlin: Julius Springer; 1910.</ref> Its toxicity and parenteral administration limited its use; its conceptual importance was immense. A quarter century later [[wikipedia:Gerhard Domagk|Gerhard Domagk]] at [[wikipedia:IG Farben|IG Farbenindustrie]] in Wuppertal-Elberfeld found that the red azo dye sulfamidochrysoidine, given under the trade name Prontosil, protected mice from lethal streptococcal infection; he reported the work in 1935 after a private trial in his own daughter, who had a streptococcal arm infection that was about to be amputated.<ref name="domagk1935">Domagk G. Ein Beitrag zur Chemotherapie der bakteriellen Infektionen. ''Deutsche Medizinische Wochenschrift''. 1935;61(7):250-253.</ref> Within a year the Bovet group at the [[wikipedia:Pasteur Institute|Pasteur Institute]] showed that the active metabolite was the colourless aminobenzenesulfonamide, sulfanilamide, whose patent had expired in 1908; a class of inexpensive synthetic antibacterials, the [[wikipedia:Sulfonamide|sulfonamides]], became available worldwide within months. Domagk was awarded the Nobel Prize in 1939 and was forced by the Nazi regime to decline it.

The natural-product era opened, more famously, with [[wikipedia:Alexander Fleming|Alexander Fleming]]'s observation in September 1928 at St Mary's Hospital in London that a stray contaminant ''[[wikipedia:Penicillium|Penicillium]]'' colony on a discarded staphylococcus plate had cleared a halo around itself.<ref name="fleming1929">Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. ''British Journal of Experimental Pathology''. 1929 Jun;10(3):226-236.</ref> Fleming named the active substance penicillin but did not pursue its purification, and it lay essentially dormant for a decade. In 1940 [[wikipedia:Howard Florey|Howard Florey]], [[wikipedia:Ernst Chain|Ernst Chain]], and [[wikipedia:Norman Heatley|Norman Heatley]] at the Sir William Dunn School of Pathology in Oxford concentrated enough penicillin from mould broth to test in mice, and in February 1941 they treated their first human patient, the Oxford policeman Albert Alexander, who recovered briefly before the supply ran out.<ref name="abraham1941">Abraham EP, Chain E, Fletcher CM, Florey HW, Gardner AD, Heatley NG, Jennings MA. Further observations on penicillin. ''Lancet''. 1941 Aug 16;238(6155):177-189.</ref> Production at the scale required for clinical use was solved in 1942-1944 by a U.S. War Production Board collaboration with the Northern Regional Research Laboratory in Peoria, Illinois, where Mary Hunt's mouldy cantaloupe yielded the high-producing strain ''[[wikipedia:Penicillium chrysogenum|Penicillium chrysogenum]]'' and deep-tank submerged fermentation replaced the surface cultures of the Oxford team. By D-Day in June 1944 there was enough penicillin to treat every Allied casualty. Fleming, Florey, and Chain shared the 1945 Nobel Prize.

The decade after penicillin was the most productive in the history of antibacterial chemistry, and the man at the centre of it was the Russian-born American microbiologist [[wikipedia:Selman Waksman|Selman Waksman]] at the Rutgers Agricultural Experiment Station. Waksman had spent his career studying soil actinomycetes and had coined the term '''antibiotic''' for their secondary metabolites in 1942. In 1943 his graduate student [[wikipedia:Albert Schatz|Albert Schatz]] isolated streptomycin from ''Streptomyces griseus'', the first medicine effective against ''[[wikipedia:Mycobacterium tuberculosis|Mycobacterium tuberculosis]]''; Waksman received the Nobel Prize in 1952 and Schatz, after years of dispute, was credited as co-discoverer.<ref name="schatz1944">Schatz A, Bugie E, Waksman SA. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. ''Proceedings of the Society for Experimental Biology and Medicine''. 1944 Jan;55(1):66-69.</ref> Chloramphenicol (1947, Burkholder, then Parke-Davis), chlortetracycline (Aureomycin, 1948, [[wikipedia:Benjamin Duggar|Benjamin Duggar]] at Lederle, from ''Streptomyces aureofaciens''), neomycin (1949), [[Erythromycin|erythromycin]] (1952, Lilly, from a soil sample from the central Philippine island of Iloilo), [[Vancomycin|vancomycin]] (1956, Lilly, from a sample of Borneo soil sent in by a missionary), and the cephalosporins (1948, [[wikipedia:Giuseppe Brotzu|Giuseppe Brotzu]] at the University of Cagliari, from a Sardinian sewage outflow, developed in Oxford and brought to clinical use by Lilly in 1964 as cephalothin) followed in steady succession.

The synthetic antibacterials of the second half of the century filled in gaps the natural products did not cover. The [[:Category:Nitroimidazoles|nitroimidazole]] metronidazole was developed at Rhône-Poulenc in 1959 for trichomoniasis and was found to be active against anaerobic bacteria as well. The first [[wikipedia:Quinolone antibiotic|quinolone]], nalidixic acid, was isolated by [[wikipedia:George Lesher|George Lesher]] at Sterling-Winthrop in 1962 as a side product of chloroquine synthesis; the introduction of a fluorine atom at the 6-position of the quinolone nucleus in the late 1970s yielded norfloxacin (1980) and then [[Ciprofloxacin|ciprofloxacin]] (1987), broad-spectrum oral agents with a respiratory- and urinary-tract niche the natural-product antibiotics had filled poorly.<ref name="lesher1962">Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP. 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents. ''Journal of Medicinal Chemistry''. 1962 Sep;5:1063-1065. PMID 14056431.</ref> The carbapenems, beginning with imipenem in 1985, extended the beta-lactam spectrum to most Gram-negative pathogens including ''Pseudomonas'', and the oxazolidinone linezolid (2000) and the cyclic lipopeptide daptomycin (2003) restored activity against vancomycin-resistant Gram-positive bacteria when no other option remained.

The phenomenon of bacterial resistance is as old as the medicines themselves. [[wikipedia:Penicillinase|Penicillinase]] from ''[[wikipedia:Staphylococcus aureus|Staphylococcus aureus]]'' was reported by [[wikipedia:Edward Abraham|Abraham]] and Chain in 1940, before penicillin had ever been given to a patient.<ref name="abraham1940">Abraham EP, Chain E. An enzyme from bacteria able to destroy penicillin. ''Nature''. 1940 Dec 28;146:837.</ref> By 1944 a third of the staphylococci in the wards at Hammersmith Hospital were penicillin-resistant; methicillin was introduced in 1959 specifically to evade the staphylococcal beta-lactamase, and methicillin-resistant ''S. aureus'' (MRSA) was reported in 1961, two years later. Vancomycin-resistant enterococci appeared in 1988, the Klebsiella pneumoniae carbapenemase in 1996, the New Delhi metallo-beta-lactamase in 2008. The accumulation of resistance mechanisms has steadily compressed the useful pharmacopoeia in some clinical settings, particularly the intensive-care unit and the long-term-care facility, and the rate at which new antibacterial classes are developed has not kept pace; only the oxazolidinones, the lipopeptides, the lipoglycopeptides, and, more recently, the siderophore cephalosporin cefiderocol, represent genuinely novel mechanisms reaching clinical use since 2000.<ref name="boucher2009">Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. ''Clinical Infectious Diseases''. 2009 Jan 1;48(1):1-12. PMID 19035777.</ref>

The contemporary use of an antibacterial in a person who is acutely ill is, in principle, a question of three judgments: which organism is likely, which medicines retain activity against it in this population at this time, and what dose and duration deliver enough medicine to the site of infection. The first is the work of clinical reasoning and laboratory diagnosis; the second is the work of local antibiogram surveillance; the third is the work of pharmacokinetics and the [[:Category:Drug-metabolizing_enzymes|drug-metabolising enzyme]] pages indexed elsewhere in this wiki. The antibacterials are also the class most often given inappropriately, and antimicrobial stewardship, the structured limitation of unnecessary prescribing, is now a recognised hospital and outpatient discipline.

== Classes indexed ==

By mechanism and structure:

* [[:Category:Beta-lactam_antibiotics|Beta-lactam antibiotics]]: the [[:Category:Penicillins|penicillins]] (Penicillin G, Penicillin V, the [[:Category:Aminopenicillins|aminopenicillins]] including amoxicillin) and the [[:Category:Cephalosporins|cephalosporins]] (cephalexin, cefuroxime, cefdinir, and successively broader-spectrum generations)
* [[:Category:Macrolide_antibiotics|Macrolides]] and the related [[:Category:Azalides|azalides]]: erythromycin, [[Azithromycin|azithromycin]], [[wikipedia:Clarithromycin|clarithromycin]]
* [[:Category:Tetracycline_antibiotics|Tetracyclines]]: doxycycline, [[wikipedia:Tetracycline|tetracycline]], [[wikipedia:Minocycline|minocycline]]
* [[:Category:Aminoglycosides|Aminoglycosides]]: [[Tobramycin|tobramycin]], [[wikipedia:Gentamicin|gentamicin]], [[wikipedia:Amikacin|amikacin]]
* [[:Category:Fluoroquinolones|Fluoroquinolones]]: [[Ciprofloxacin|ciprofloxacin]], [[Levofloxacin|levofloxacin]], [[Moxifloxacin|moxifloxacin]], [[Ofloxacin|ofloxacin]]
* [[:Category:Lincosamides|Lincosamides]]: [[Clindamycin|clindamycin]]
* [[:Category:Nitroimidazoles|Nitroimidazoles]]: [[Metronidazole|metronidazole]]
* [[:Category:Nitrofurans|Nitrofurans]]: [[Nitrofurantoin|nitrofurantoin]]
* Glycopeptides and lipoglycopeptides (where built): vancomycin, telavancin, dalbavancin
* [[:Category:Antifolates|Antifolates]] (sulfonamides combined with trimethoprim are the principal antibacterial application of this class)
* Topical antibacterials are collected separately under [[:Category:Topical_antibiotics|topical antibiotics]] and include [[Mupirocin|mupirocin]]

== Notes on scope ==

The boundary of this category is "medicine that kills or inhibits bacterial pathogens in the human host." Antiviral agents, antifungal agents, and antiparasitic agents are collected separately. Antiseptics and disinfectants (chlorhexidine, povidone-iodine, hypochlorite) act on bacterial surfaces but are not administered systemically and are collected under [[:Category:Antiseptics|antiseptics]]. Antimycobacterial agents (isoniazid, rifampin, ethambutol, pyrazinamide, the fluoroquinolones when used for tuberculosis) belong taxonomically here but are listed under a dedicated subcategory when their principal indication is mycobacterial. Topical preparations whose principal indication is dermatologic or ophthalmic are also listed under the appropriate route-specific category in addition to this one.

== About these pages ==

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.

== References ==

<references/>

[[Category:Medicines]]
[[Category:Anti-infectives]]
[[Category:CuratedCategoryPage]]

Category:Antibacterials - Revision history

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