Timeline of antibiotics

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This is a timeline of antibiotics, mainly focusing on both the introduction of drugs and first reported drug resistances. For historic events focusing on bacteria, visit Timeline of bacteriology.

Big picture

Time period Development summary
<19th century Although people did not know infections were caused by bacteria, antibiotics have been used for millennia to treat infections. Some of the earliest civilizations used various molds and plant extracts for treatment. The ancient Egyptians, for example, applied mouldy bread to infected wounds.[1]
19th century Scientists begin to observe antibacterial chemicals in action.[1] By the late century, a few notable breakthroughs occur.
20th century Antibiotics revolutionize medicine during the later half of the 20th century.[2] The major event in the history of antibiotics is the discovery of penicillin by Alexander Fleming in 1928. The first antibiotics are prescribed in the late 1930s.[3] The period between the 1950s and 1970s is considered the golden era of discovery of novel antibiotics classes, with no new classes discovered since then.[4] In fact, between 1944 and 1972 human life expectancy jumps by eight years, largely due to the introduction of antibiotics.[3] In the 1970s and 1980s synthetic versions of erythromycin, including clarithromycin and azithromycin, are developed.[5] After the 1970s, with the decline of the discovery rate, the mainstream approach for the development of new drugs to combat emerging and re-emerging resistance of pathogens to antibiotics would be the modification of existing antibiotics.[4] By the 1980s and 1990s, scientists only manage to make improvements within classes.[6]
21th century At present, there are more than 100 antibiotics available to treat human and animal diseases.[7]

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Full timeline

Year Event type Details Geographical location
350 CE–550 CE Traces of tetracycline are found in human skeletal remains from ancient Sudanese Nubia.[4][2]
1877 Scientific development French microbiologist Louis Pasteur shows that the bacterial disease anthrax can be rendered harmless in animals with the injection of soil bacteria.[8][9] France
1887 Scientific development German bacteriologist Rudolf Emmerich shows that the intestinal infection cholera is prevented in animals that have been previously infected with the streptococcus bacterium and then injected with the cholera bacillus.[10]
1888 Scientific development German scientist E. de Freudenreich manages to isolate an actual product from a bacterium that had antibacterial properties.[11]
1896 Scientific development French medical student Ernest Duchesne originally discovers the antibiotic properties of Penicillium.[12][13][14]
1897 Resistance Doctoral student Ernest Duchesne submits a dissertation, Contribution à l'étude de la concurrence vitale chez les micro-organismes: antagonisme entre les moisissures et les microbes (Contribution to the study of vital competition in micro-organisms: antagonism between molds and microbes), the first known scholarly work to consider the therapeutic capabilities of molds resulting from their anti-microbial activity. In his thesis, Duchesne proposes that bacteria and molds engage in a perpetual battle for survival.[15] France
1907 New drug German chemist Alfred Bertheim and Paul Ehrlich discover arsenic-derived synthetic antibiotics. This marks the beginning of the era of antibacterial treatment.[16]
1909 Scientific development Japanese bacteriologist Sahachiro Hata discovers the antisyphilitic activity of arsphenamine.[1][17]
1912 New drug Paul Ehrlich discovers Neosalvarsan, a synthetic chemotherapeutic.[18]
1928 New drug Scottish microbiologist Alexander Fleming, a Professor of Bacteriology at St Mary’s Hospital in London, discovers penicillin after sorting through some petri dishes containing a bacteria called staphylococcus, which causes boils, sore throats and abscesses. Flemming discovers killed baceria in one dish contaning a blob of mold on it.[11][5] United Kingdom
1930 Scientific development French-born American microbiologist René Dubos isolates from a soil microorganism an enzyme that can decompose part of the bacillum that causes lobar pneumonia in humans.[19]
1932 New drug German pathologist Gerhard Domagk develops prontosil, the first sulphonamide microbial.[20][21][22] Germany
1936 New drug Sulfonamide antibacterial sulfanilamide is introduced in the United States and is immediately established as a powerful antiinfective agent.[23] United States
1937 New drug The first effective antimicrobials (sulfonamides) are introduced.[24]
1938 New drug Sulfapyridine is introduced for clinical use for the treatment of pneumococcic pneumonia.[25][26] Today it is used to help control dermatitis herpetiformis (Duhring's disease), a skin problem.[27]
1939 Scientific development Microbiologist René Dubos manages to isolate an antibacterial substance and names it tyrothricin.[19]
1939 New drug Gramicidin A is discovered from the soil bacterium bacillus brevis, and becomes the first clinically useful topical antibiotic.[28][29][30]
1939 Scientific development Australian pharmacologist Howard Florey and Ernst Boris Chain manage to elucidate the structure of penicillin G, the first penicillin used in therapy.[31][32][33]
1939 New drug Sulfonamide antibiotic sulfacetamide is first reported in the treatment of diseases of the eye.[34][35] Today it is used to treat bacterial eye infections, such as conjunctivitis.[36]
1940 New drug Sulfonamide antibiotic sulfamethizole is introduced and marketed as a single compound for the treatment of urinary tract infections.[37][38][39]
1941 New drug β-lactam antibiotics enter initial clinical trials. In time, they would become the most widely produced and used antibacterial drugs in the world.[40][41] β-lactam antibiotics now the most economically important of all the groups of antimicrobials.[42]
1941 New drug Penicillin is introduced for medical use.[43][22] Just before the introduction of penicillin, the mortality rate from Staphylococcus aureus infections that had reached the blood stream was reported to be 80%.[43]
1942 New drug Sulfadimidine is introduced for the treatment of bacterial infections.[44][45][46][47]
1942 Resistance Penicillin resistant bacteria are first detected, about one year after the introduction of penicillin.[43]
1942 New drug Gramicidin S, the first peptide antibiotic, is isolated by Gauze and Brazhnikova.[48][49][50]
1943 New drug American biochemists Selman Waksman, Albert Schatz, and Elizabeth Bugie discover antibiotic streptomycin, the first aminoglycoside. It is the first antibiotic effective against tuberculosis.[5][51][52][53][22] United States
1943 New drug Sulfamerazine is synthesized by American chemists.[54] The drug is today used as an antibacterial agent.[55][56][57][58] United States
1943 Production Penicillin is mass produced and used heavily to treat Allied troops fighting in Europe during World War II.[2]
1943 New drug Bacitracin is first isolated.[59][60] The drug is used to prevent minor skin infections caused by small cuts, scrapes, or burns.[61]
1945 New drug The cephalosporins are discovered from a fungus, Cephalosporium acremonium, in seawater samples near a sewage outfall in Sardinia.[22][62][63][64] Italy
1947 New drug Chloramphenicol is isolated from the soil organism Streptomyces venezuelae. Merketed in 1949, its use would quickly become widespread due to its broad spectrum of antimicrobial activity.[65][66][67][68]
1947 New drug American plant physiologist Benjamin Minge Duggar isolates chlortetracycline from a Missouri River mud sample. It is the first tetracycline introduced.[69][70][71][72] United States
1947 New drug The polymyxin family of antibiotics is discovered, with polymyxin B being the first isolated from bacterium paenibacillus polymyxa.[5][73][74]
1947 New drug Drug class Nitrofuran is introduced.[40] Nitrofurans are synthetic chemotherapeutic agents with a broad antimicrobial spectrum, active against both gram-positive and gram-negative bacteria, including salmonella and Giardia spp, trichomonads, amebae, and some coccidial species.[75]
1948 New drug Mafenide –a sulfonamide-type antibiotic, is approved by the United States FDA.[76][77]
1949 New drug Jewish-American biochemist Selman Waksman and Hubert A. Lechevalier first isolates neomycin, as aminoglycoside antibiotic found in many topical medications such as creams, ointments, and eyedrops.[78][79][80] United States
1949 Scientific development British chemist Dorothy Hodgkin reveals the complete structure of molecular penicillin, using the X-ray crystallography.[24] United Kingdom
1950 New drug Oxytetracycline comes into commercial use.[60][81][82] Since then, this antibiotic would be used widely in human and veterinary medicine.[83]
1950 Resistance Resistance against chloramphenicol is observed.[84]
1952 New drug Lincosamides are introduced.[40] A small group of agents with a novel structure unlike that of any other antibiotic, lincosamides are widely active against Gram-positive bacteria and most anaerobes, with the exception of Gram-negative aerobes. Lincosamides are also active against some mycoplasmas and protozoa.[85]
1952 New drug Antibiotic thiamphenicol is first synthesized.[86] It is a broad spectrum antibiotic with good activity against Gram negative and anaerobic bacteria.[87]
1952 New drug Eli Lilly and Company introduces erythromycin, an antibiotic useful for the treatment of a number of bacterial infections, including respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis.[88][89][90] Erythromycin is the first macrolide antibiotic.[91] United States
1952 New drug Streptogramins are introduced. Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant Enterococcus (VRE), two of the most rapidly growing strains of multidrug-resistant bacteria.[40]
1953 New drug Oxford University scientists discover antibiotic cephalosporin C, from which cephalosporins later develop. Like penicillins, cephalosporins inhibit cell wall synthesis by preventing cross-linking of peptidoglycan.[92][5] United Kingdom
1953 Resistance Macrolide resistance is observed.[40]
1954 New drug Benzathine penicillin is established as a method for the treatment of syphilis.[93]
1954 New drug Antibiotic cycloserine is discovered. It is used for the treatment of tuberculosis.[94][95]
1955 New drug Macrolide antibiotic spiramycin is first introduced into the French market.[96] Spiramycin is used to treat various infections.[97] France
1956 New drug Research team at the Lilly Biological Laboratories in Indiana first isolates vancomycin from bacterium streplomyces orienlalis. Vancomycin is used as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant staphylococcus aureus.[22][98][99][100] United States
1956 Resistance Resistance against erythromycin is observed.[84]
1957 New drug Kanamycin is discovered. It is used to treat severe bacterial infections and tuberculosis.[60]
1957 New drug Ansamycins are introduced. These bacterial secondary metabolites show antimicrobial activity against many Gram-positive and some Gram-negative bacteria.[40]
1959 New drug Colistin becomes available for treating infections caused by gram-negative bacteria.[5]
1959 New drug Nitroimidazoles are introduced. They are effective bactericidal agents against anaerobes and protozoa.[40]
1960 New drug In an attempt to defeat penicillin-resistant strains, scientists develop methicillin, a different antibiotic in the penicillin class.[2][84]
1960 New drug Metronidazole is commercially introduced as an effective antitrichomonal agent. Since then, its use would be extended to the treatment of amebiasis, giardiasis, nonspecific vaginitis, and anaerobic infections, including upper genital tract infections.[101][102][103]
1961 Resistance Methicillin resistance is first reported.[43][84][40]
1961 New drug Antibiotic ampicillin is introduced. Within a short time it would become the drug of choice for treatment of Hemophilus influenzae meningitis.[104][105][106][22]
1961 Resistance Methicillin-resistant staphylococcus aureus is first reported in the United Kingdom, just a year after the antibiotic methicillin was introduced in the country.[5]
1961 New drug Spectinomycin is first reported. Today it is used for the treatment of gonorrhea infections.[107][60]
1961 New drug Ethambutol is discovered. The medication is primarily used for the treatment of tuberculosis.[108][109][110]
1962 New drug The fusidic acid is introduced into clinical practice.[111] The antibiotic is prescribed for skin infections caused by staphylococcal bacteria.[112]
1962 New drug Quinolones are discovered accidentally, as a byproduct of some research on the antimalarial drug chloroquine.[5][40]
1963 New drug Weinstein and his colleagues from the Schering Corporation describe the first isolation of the gentamicin complex.[22][113][114][115] United States
1963 New drug Gentamicin is discovered. It is used to treat several types of bacterial infections.[60]
1963 Resistance Gram-negative bacterium acinetobacter baumannii becomes an antibiotic resistant pathogen.[43]
1965 New drug Antibiotic Cloxacillin synthesized. Today it is useful for the treatment of a number of bacterial infections,[116] including impetigo, cellulitis, pneumonia, septic arthritis, and otitis externa.[116] It is used by mouth and by injection.[116].[117][118][119]
1966 Resistance Nalidixic acid resistance is observed.[40]
1966 New drug Antibiotic doxycycline is synthesized.[120][121][122] Today it is used for bacterial pneumonia, acne, chlamydia infections, early Lyme disease, cholera and syphilis.[123]
1966 Resistance Resistance against cephalotin is observed.[84]
1967 New drug Clindamycin is first produced. Today it is used for the treatment of a number of bacterial infections.[60]
1968 New drug Antibiotic rifampicin is introduced for clinical use.[124][125][126] The introduction of rifampicin would greatly shorten the duration of tuberculosis chemotherapy.[127] Italy
1968 Resistance Tetracycline resistance is observed.[40][40]
1968 New drug Trimethoprim is introduced. It is used mainly in the treatment of bladder infections.[40]
1969 New drug Fosfomycin (originally named phosphonomycin) is discovered in Spain. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae.[128][129][130] Spain
1970 New drug Non-toxic semi-synthetic acid-resistant isoxazolyl penicillin flucloxacillin is introduced into clinical practice.[119][131]
1971 New drug Aminoglycoside antibiotic Tobramycin is discovered. It is used to treat various types of bacterial infections, particularly Gram-negative infections.[60]
1971 New drug Mupirocin is originally isolated from Pseudomonas fluorescens.[132] The antibiotic is primarily effective against Gram-positive bacteria.[133]
1972 New drug Extracellular broad spectrum beta-lactam antibiotic cephamycin C is first isolated.[134][60]
1972 New drug Antibiotic minocycline is discovered.[120][121][122] It has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne.[135]
1972 New drug Tinidazole is introduced.[136] It is an anti-parasitic drug used against protozoan infections.[137]
1973 New drug Bactericidal antibiotic Carbenicillin is discovered. It belongs to the carboxypenicillin subgroup of the penicillins.[138] Carbenicillin has bactericidal and beta-lactamase resistant activity.[139]
1974 New drug Antibiotic trimethoprim/sulfamethoxazole is commercially released.[140][22]
1974 New drug Cotrimoxazole is introduced.[60] It is used to treat certain bacterial infections, such as pneumonia, bronchitis, and infections of the urinary tract, ears, and intestines. Cotrimoxazole also is used to treat 'travelers' diarrhea.[141]
1976 New drug The Bristol-Banyu research institute in Japan publishes the discovery of antibiotic amikacin.[22][60][142] Amikacin is active against a broad spectrum of Gram-negative organisms, including pseudomonas, Escherichia coli and some Gram-positive organisms, like Staphylococcus aureus.[143] Japan
1976 Resistance Tufts University researcher Stuart B. Levy becomes one of the first to identify antibiotic resistance due to their use in animals.[2]
1978 New drug Cefoxitin is introduced as an early cephamycin.[138][144] It is synthesized in order to create an antibiotic with a broader spectrum.[145]
1978 New drug The teicoplanin family of glycopeptides is discovered.[146] Teicoplanin is used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis.[147]
1979 New drug Eli Lilly patents antibiotic cefaclor.[148][149][150] It is used to treat certain bacterial infections such as pneumonia and infections of the ear, lung, skin, throat, and urinary tract. United States
1981 Resistance AmpC beta-lactamase resistance is observed.[40]
1981 New drug Researchers at Bayer discover ciprofloxacin, the first fluoroquinolone. Ciproloxacin is used to treat bone and joint infections, intra abdominal infections, certain type of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others.[151]
1983 Resistance Extended-spectrum-beta-lactamase resistance is observed.[40]
1984 New drug amoxicillin clavulanate is introduced.[60] It is specifically used for otitis media, strep throat, pneumonia, cellulitis, urinary tract infections, animal bites, and tuberculosis.[152]
1985 New drug Researchers at Eli Lilly and Company discover antibiotic daptomycin.[153][154][155] United States
1985 New drug Carbapenems are introduced.[84] These are commonly used for the treatment of severe or high-risk bacterial infections.
1986 Resistance Vancomycin-resistant enterococcus is reported.[84][40]
1987 New drug Antibiotic imipenem/cilastin is introduced.[22] It is useful for the treatment of pneumonia, sepsis, endocarditis, joint infections, intra-abdominal infections, and urinary tract infections.[156]
1987 New drug Highly potent fluoroquinolones are introduced.[24] These are used to treat a variety of illnesses such as respiratory and urinary tract infections.[157] These popular class of antibiotics would be used in a variety of infections. Newer drugs in this class are further developed with a broader spectrum of activity including better coverage of gram-positive organisms and, for some fluoroquinolones, anaerobes.[158]
1987 Resistance Resistance against cephalosporins is observed.[84]
1987 Resistance Resistance against carbapenems is observed.[84]
1990s Resistance Fluorochinolone resistance is observed.[40]
1993 New drug Antibiotic azithromycin is introduced.[22] It is used to treat certain bacterial infections, such as bronchitis, pneumonia, sexually transmitted diseases (STD), and infections of the ears, lungs, sinuses, skin, throat, and reproductive organs.[159]
1993 New drug Antibiotic clarithromycin is introduced.[22] It is used to prevent and treat certain infections caused by bacteria.[160]
1994 New drug Cefepime is introduced into clinical practice. Approved for the treatment of moderate-to-severe infections, such as pneumonia, uncomplicated and complicated urinary tract infections (UTIs), skin and soft-tissue infections, intra-abdominal infections and febrile neutropenia.[161]
1997 Resistance Vancomycin-resistant staphyloccocus is reported.[40]
1999 New drug Antibiotic quinupristin/dalfopristin is introduced.[22] The combination is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium.
2000 New drug Oxazolidinones are introduced.[40] These synthetic drugs are active against a large spectrum of Gram-positive bacteria, including methicillin- and vancomycin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant pneumococci and anaerobes.[162]
2000 New drug Antibiotic linezolid is introduced for the treatment of infections caused by gram-positive bacteria that are resistant to other antibiotics.[22][84] An oxazolidinone antibiotic, linezolid represents the first principally new antibiotic platform that has entered medical practice in more than 30 years.[163][40]
2001 New drug Antibiotic telithromycin is introduced in the European Union.[164][165][166] It is used to treat certain types of pneumonia.[167]
2001 New drug Broader-spectrum fluoroquinolones are introduced.[138]
2002 Resistance Resistance against linezolid is observed.[84]
2002 New drug The United States Food and Drug Administration approves cefditoren, pivoxil and ertapenem. [168][60]
2002 Resistance Vancomycin-resistant staphylococcus aureus is reported.[40]
2003 New drug Lipopeptides are introduced as antibiotics.[40]
2003 New drug Daptomycin (a lipopeptide antibiotic) is introduced for treatment of systemic and life-threatening infections caused by Gram-positive organisms.[22][169][170]
2004 New drug Telythromicin is introduced.[60] It is used to treat certain types of pneumonia.[171]
2005 New drug Antibiotic tigecycline is introduced for the treatment of skin and skin structure infections and intraabdominal infections.[172][173][174]
2010 Publication Authors of a report on the evolution of resistance note that microbes have “extraordinary genetic capabilities” that benefit “from man’s overuse of antibiotics to exploit every source of resistance genes... to develop [resistance] for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise.”[2]
2011 New drug The United States Food and Drug Administration approves fidaxomicin for treatment of clostridium Difficile Infection.[175][176] United States
2012 Study A team of scientists propose adding the terms extensively drug-resistant (XDR) and pandrug-resistant (PDR) to multidrug-resistant (MDR) bacteria to better help them classify and potentially defeat superbugs.[2]
2012 New drug The United States Food and Drug Administration approves bedaquiline for the treatment of multidrug-resistant tuberculosis.[177][178] United States
2013 New drug The United States Food and Drug Administration approves telavancin for the treatment of hospital-acquired pneumonia caused by susceptible staphylococcus aureus.[179][180][181] United States
2013 Resistance The US Centers for Disease Control and Prevention identifies 17 antibiotic-resistant microorganisms that cause at least 23,000 deaths in the United States.[7] United States
2014 Declaration The World Health Organization (WHO) releases a statement in response to major superbug outbreaks like lebsiella pneumoniae (which causes pneumonia and bloodstream infections in the hospital) and gonorrhea strains all over the world, noting that “this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country.”[2]
2014 New drug The United States Food and Drug Administration approves four new antibacterial agents, dalbavancin, oritavancin, tedizolid for skin infections, and ceftolozane/tazobactam for complicated intra‐abdominal and urinary tract infections.[182] United States
2015 Policy American fast food company McDonald's announces that it would phase out all meat sources that contain antibiotics.[2]
2015 New drug Ceftazidime/avibactam is introduced for use in the United States.[183][184][185] The combination is used for treatment against certain multidrug-resistant Gram-negative infections. United States
2015 New drug Natural antibiotic teixobactin is discovered in a screen of uncultured bacteria. It is found to kill pathogens without detectable resistance.[186][187]
2017 New drug Scientists produce new, effective and simplified forms of teixobactin - a new generation antibiotic which defeats multi-drug resistant infections such as Methicillin-resistant Staphylococcus aureus. The research moves closer to defeating 'superbugs' with simplified forms of the drug.[188]
2018 New drug The discovery of malacidins is published.[189] The novel antibiotic can work against many of the multidrug-resistant bacterial strains.[190]

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References

  1. ↑ 1.0 1.1 1.2 "THE HISTORY OF ANTIBIOTICS". microbiologysociety.org. Retrieved 29 March 2018. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "A Brief History Of Antibiotic Resistance: How A Medical Miracle Turned Into The Biggest Public Health Danger Of Our Time". medicaldaily.com. Retrieved 29 March 2018. 
  3. ↑ 3.0 3.1 "antibiotics 1928-2000". abc.net.au. Retrieved 31 March 2018. 
  4. ↑ 4.0 4.1 4.2 Aminov, Rustam I. "A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future". PMC 3109405Freely accessible. PMID 21687759. doi:10.3389/fmicb.2010.00134. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 "Ten important moments in the history of antibiotic discovery". correctiv.org. Retrieved 29 March 2018. 
  6. ↑ "A brief history of antibiotics". news.bbc.co.uk. Retrieved 30 March 2018. 
  7. ↑ 7.0 7.1 "Antibiotics". sciencedirect.com. Retrieved 11 July 2018. 
  8. ↑ Tierno, Philip M. The Secret Life of Germs: What They Are, Why We Need Them, and How We Can Protect Ourselves Against Them. 
  9. ↑ Williams, Elizabeth S.; Barker, Ian K. Infectious Diseases of Wild Mammals. 
  10. ↑ Newell-McGloughlin, Martina; Re, Edward. The Evolution of Biotechnology: From Natufians to Nanotechnology. 
  11. ↑ 11.0 11.1 Newell-McGloughlin, Martina; Re, Edward. The Evolution of Biotechnology: From Natufians to Nanotechnology. 
  12. ↑ Zhang, Yawei. Encyclopedia of Global Health, Volume 1. 
  13. ↑ Myers, Richard L. The 100 Most Important Chemical Compounds: A Reference Guide. 
  14. ↑ Manning, Shannon D.; Alcamo, I. Edward; Heymann, David L. Escherichia Coli Infections. 
  15. ↑ Duchesne E. Duchesne's Antagonism between molds and bacteria, an English Colloquial Translation. Translated by Witty M. Amazon.com. ASIN B00DZVXPIK. ISBN 978-1-5498-1696-3. 
  16. ↑ SWATHY, S; ARYA, US. "ANTIBIOTIC USAGE IN PEDIATRICS" (PDF). INTERNATIONAL JOURNAL FOR INNOVATIVE RESEARCH IN MULTIDISCIPLINARY FIELD. 
  17. ↑ Thomas, Gareth. Medicinal Chemistry: An Introduction. 
  18. ↑ "Neosalvarsan". sciencedirect.com. Retrieved 1 April 2018. 
  19. ↑ 19.0 19.1 "René Dubos". britannica.com. Retrieved 30 March 2018. 
  20. ↑ Ravina, Enrique. The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. 
  21. ↑ Savona-Ventura, Charles. Contemporary Medicine in Malta [1798-1979]. 
  22. ↑ 22.00 22.01 22.02 22.03 22.04 22.05 22.06 22.07 22.08 22.09 22.10 22.11 22.12 22.13 22.14 Torok, Estee; Moran, Ed; Cooke, Fiona. Oxford Handbook of Infectious Diseases and Microbiology. 
  23. ↑ HUGHES, RAYMOND P. "THE USE OF SULFANILAMIDE IN DERMATOLOGY". doi:10.1001/archderm.1940.01490130037006. 
  24. ↑ 24.0 24.1 24.2 Davies, Julian; Davies, Dorothy. "Origins and Evolution of Antibiotic Resistance" (PDF). doi:10.1128/MMBR.00016-10. 
  25. ↑ "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". karger.com. Retrieved 1 April 2018. 
  26. ↑ DETWEILER, H. K.; KINSEY, H. I.; HURST, W. "TREATMENT OF PNEUMONIA WITH SULFAPYRIDINE". 
  27. ↑ "Sulfapyridine (Oral Route)". mayoclinic.org. Retrieved 2 May 2018. 
  28. ↑ Bhattacharjee, Mrinal K. Chemistry of Antibiotics and Related Drugs. 
  29. ↑ Mouritsen, Ole G. Life - As a Matter of Fat: The Emerging Science of Lipidomics. 
  30. ↑ Current Topics in Membranes and Transport, Volume 33. 
  31. ↑ Stadler, Marc; Dersch, Petra. How to Overcome the Antibiotic Crisis: Facts, Challenges, Technologies and Future Perspectives. 
  32. ↑ Persson, Sheryl. Smallpox, Syphilis and Salvation: Medical Breakthroughs that Changed the World. 
  33. ↑ Smallman-Raynor,, Matthew; Cliff, Andrew. Atlas of Epidemic Britain: A Twentieth Century Picture. 
  34. ↑ DUEMLING, WERNER W. "SODIUM SULFACETAMIDE IN TOPICAL THERAPY". 
  35. ↑ DUEMLING, WERNER W. "SODIUM SULFACETAMIDE IN TOPICAL THERAPY". doi:10.1001/archderm.1954.01540130077007. 
  36. ↑ "Sulfacetamide Sodium Drops". webmd.com. Retrieved 2 May 2018. 
  37. ↑ Vree, T.B. "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". doi:10.1159/000414195. 
  38. ↑ Vree, Tom B.; Aaron, Yechiel; Karger, Hekster S. Antibiotics and Chemotherapy, Volume 37. 
  39. ↑ The New Yorker, Volume 45, Part 2. 
  40. ↑ 40.00 40.01 40.02 40.03 40.04 40.05 40.06 40.07 40.08 40.09 40.10 40.11 40.12 40.13 40.14 40.15 40.16 40.17 40.18 40.19 40.20 40.21 "Antibiotics armageddon?". mega.online. Retrieved 31 March 2018. 
  41. ↑ "Beta lactam antibiotics". slideshare.net. Retrieved 2 May 2018. 
  42. ↑ "β-Lactam Antibiotics". sciencenutshell.com. Retrieved 2 May 2018. 
  43. ↑ 43.0 43.1 43.2 43.3 43.4 Landecker, Hannah. "Antibiotic Resistance and the Biology of History". 
  44. ↑ [Consolidated list of products whose consumption and/or sale have been banned, withdrawn, severely restricted or not approved by governments / Pharmaceuticals ] ; Consolidated list of products whose consumption and/or sale have been banned, withdrawn, severely restricted or not approved by governments. Pharmaceuticals. United Nations. 
  45. ↑ "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". karger.com. Retrieved 1 April 2018. 
  46. ↑ [Consolidated list of products whose consumption and/or sale have been banned, withdrawn, severely restricted or not approved by governments / Pharmaceuticals ] ; Consolidated list of products whose consumption and/or sale have been banned, withdrawn, severely restricted or not approved by governments. Pharmaceuticals. United Nations. 
  47. ↑ Vree, Tom B.; Hekster, Yechiel Aaron. Antibiotics and Chemotherapy, Volume 37. 
  48. ↑ Berditsch, Marina; Afonin, Sergii; Ulrich, Anne S. "The Ability of Aneurinibacillus migulanus (Bacillus brevis) To Produce the Antibiotic Gramicidin S Is Correlated with Phenotype Variation▿". 
  49. ↑ GAUSE, G. F.; BRAZHNIKOVA, M. G. "Gramicidin S and its use in the Treatment of Infected Wounds". Nature. doi:10.1038/154703a0. 
  50. ↑ Korzybski, Tadeusz; Kowszyk-Gindifer, Zuzanna; Kurylowicz, Wlodzimierz. Antibiotics: Origin, Nature and Properties. 
  51. ↑ Lorian, Victor. Antibiotics in Laboratory Medicine. 
  52. ↑ Morabia, Alfredo. Enigmas of Health and Disease: How Epidemiology Helps Unravel Scientific Mysteries. 
  53. ↑ Cumo, Christopher Martin. The Ongoing Columbian Exchange: Stories of Biological and Economic Transfer in World History: Stories of Biological and Economic Transfer in World History. 
  54. ↑ Boothe, Russell G. "Comparison of sulfathiazole with sulfamerazine in extraction and impaction". 
  55. ↑ "Sulfamerazine". pubchem.ncbi.nlm.nih.gov. Retrieved 2 May 2018. 
  56. ↑ Santo Tomas Journal of Medicine, Volume 3. University of Santo Tomas, College of Medicine. 
  57. ↑ Biennial Report. North Dakota. State Dept. of Health. 
  58. ↑ Nelson loose-leaf living medicine, Volume 8. T. Nelson & Sons. 
  59. ↑ "Bacitracin A". pubchem.ncbi.nlm.nih.gov. Retrieved 2 May 2018. 
  60. ↑ 60.00 60.01 60.02 60.03 60.04 60.05 60.06 60.07 60.08 60.09 60.10 60.11 60.12 "The Golden Age of Antibacterials". amrls.cvm.msu.edu. Retrieved 31 March 2018. 
  61. ↑ "Bacitracin Ointment". webmd.com. Retrieved 2 May 2018. 
  62. ↑ Stephanie Watts; Faingold, Carl; Dunaway, George; Crespo, Lynn. Brody's Human Pharmacology - E-Book. 
  63. ↑ Riviere, Jim E.; Papich, Mark G. Veterinary Pharmacology and Therapeutics. 
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  67. ↑ Shapiro, Stuart. Regulation of Secondary Metabolism in Actinomycetes. 
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  105. ↑ Thompson, R.A.; Green, John R. Infectious Diseases of the Central Nervous System. 
  106. ↑ Fifty Years of Antimicrobials: Past Perspectives and Future Trends. Society for General Microbiology. Symposium. 
  107. ↑ Bhattacharjee, Mrinal K. Chemistry of Antibiotics and Related Drugs. 
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  111. ↑ Lorian, Victor. Antibiotics in Laboratory Medicine. 
  112. ↑ "Fusidic acid for skin infections". patient.info. Retrieved 31 May 2018. 
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  118. ↑ Kuemmerle, Helmut Paul. Clinical Chemotherapy: Antimicrobial Chemotherapy. 
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  132. ↑ Carr, Tara F.; Hill, Jennifer L.; Chiu, Alex. "Alteration in Bacterial Culture After Treatment With Topical Mupirocin for Recalcitrant Chronic Rhinosinusitis". 
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  134. ↑ Diana, Patrizia; Cirrincione, Girolamo. Biosynthesis of Heterocycles: From Isolation to Gene Cluster. 
  135. ↑ Ochsendorf, F. "Minocycline in acne vulgaris: benefits and risks.". doi:10.2165/11319280-000000000-00000. Check |doi= value (help). 
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  137. ↑ "Tinidazole Pellets". pharmaceuticalpellets.com. Retrieved 31 May 2018. 
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  139. ↑ "Carbenicillin". pubchem.ncbi.nlm.nih.gov. Retrieved 12 May 2018. 
  140. ↑ "Pharmaceutical Marketing in India". books.google.com.ar. Retrieved 28 March 2018. 
  141. ↑ "Co-trimoxazole". medlineplus.gov. Retrieved 12 May 2018. 
  142. ↑ "Amikacin". tbonline.info. Retrieved 2 May 2018. 
  143. ↑ "Amikacin 250 mg/ml Injection". medicines.org.uk. Retrieved 2 May 2018. 
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  148. ↑ Sinha, Aseema. Globalizing India. 
  149. ↑ Amann, Edmund; Cantwell, John. Innovative Firms in Emerging Market Countries. 
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  151. ↑ "Ciprofloxacin (Cipro®)". emedexpert.com. Retrieved 12 May 2018. 
  152. ↑ "Amoxicillin and Clavulanate Potassium". The American Society of Health-System Pharmacists. Archived from the original on 29 November 2016. Retrieved 12 May 2018. 
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  154. ↑ Rybak, M. J. "The efficacy and safety of daptomycin: first in a new class of antibiotics for Gram‐positive bacteria". 
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  158. ↑ "Fluoroquinolones". uptodate.com. Retrieved 31 May 2018. 
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  164. ↑ Kucers' The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition - Three Volume Set (M. Lindsay Grayson, Sara E. Cosgrove, Suzanne Crowe, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson ed.). 
  165. ↑ Alex, Alexander; Harris, C. John; Smith, Dennis A. Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward. 
  166. ↑ Hugo and Russell's Pharmaceutical Microbiology (Stephen P. Denyer, Norman A. Hodges, Sean P. Gorman, Brendan F. Gilmore ed.). 
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  178. ↑ Villa,, Tomas G.; Vinas, Miguel. New Weapons to Control Bacterial Growth. 
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