Difference between revisions of "Timeline of antibiotics"

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| 1960 || Introduction || In an attempt to defeat penicillin-resistant strains, scientists develop {{w|methicillin}}, a different antibiotic in the penicillin class.<ref name="A Brief History Of Antibiotic Resistance: How A Medical Miracle Turned Into The Biggest Public Health Danger Of Our Time"/><ref name="Evolution in Health and Disease"/> ||
 
| 1960 || Introduction || In an attempt to defeat penicillin-resistant strains, scientists develop {{w|methicillin}}, a different antibiotic in the penicillin class.<ref name="A Brief History Of Antibiotic Resistance: How A Medical Miracle Turned Into The Biggest Public Health Danger Of Our Time"/><ref name="Evolution in Health and Disease"/> ||
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| 1960 || Introduction || {{w|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.<ref>{{cite journal |last1=Olson Robbie |first1=Marilyn |last2=Sweet |first2=Richard L. |title=Metronidazole use in obstetrics and gynecology: A review |journal=American Journal of Obstetrics and Gynecology |url=https://www.sciencedirect.com/science/article/pii/0002937883906932}}</ref><ref>{{cite book |title=Advances in Pharmacology and Chemotherapy |url=https://books.google.com.ar/books?id=8hMr2_SPXDoC&pg=PA224&dq=%22Metronidazole%22+%22in+1960%22&hl=en&sa=X&ved=0ahUKEwiGsP-t-K7bAhWEkZAKHYAACdsQ6AEIKDAA#v=onepage&q=%22Metronidazole%22%20%22in%201960%22&f=false}}</ref><ref>{{cite book |title=Progress in Medicinal Chemistry, Volume 18 |url=https://books.google.com.ar/books?id=FC9pDtB_tz0C&pg=PA88&dq=%22Metronidazole%22+%22in+1960%22&hl=en&sa=X&ved=0ahUKEwiGsP-t-K7bAhWEkZAKHYAACdsQ6AEILTAB#v=onepage&q=%22Metronidazole%22%20%22in%201960%22&f=false}}</ref>
 
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| 1961 || Resistance || {{w|Methicillin}} resistance is first reported.<ref name="Antibiotic Resistance and the Biology of History"/><ref name="Evolution in Health and Disease"/><ref name="Antibiotics armageddon?"/> ||
 
| 1961 || Resistance || {{w|Methicillin}} resistance is first reported.<ref name="Antibiotic Resistance and the Biology of History"/><ref name="Evolution in Health and Disease"/><ref name="Antibiotics armageddon?"/> ||

Revision as of 19:04, 30 May 2018

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]

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.[7][8] 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.[9]
1888 Isolation German scientist E. de Freudenreich manages to isolate an actual product from a bacterium that had antibacterial properties.[10]
1896 Scientific development French medical student Ernest Duchesne originally discovers the antibiotic properties of Penicillium.[11][12][13]
1907 Scientific development German chemist Alfred Bertheim and Paul Ehrlich discover arsenic-derived synthetic antibiotics. This marks the beginning of the era of antibacterial treatment.[14]
1909 Introduction Japanese bacteriologist Sahachiro Hata discovers the antisyphilitic activity of arsphenamine.[1][15]
1912 Introduction Paul Ehrlich discovers Neosalvarsan, a synthetic chemotherapeutic.[16]
1928 Introduction 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.[10][5] United Kingdom
1930 Isolation 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.[17]
1932 Introduction German pathologist Gerhard Domagk develops prontosil, the first sulphonamide microbial.[18][19][20] Germany
1936 Introduction Sulfonamide antibacterial sulfanilamide is introduced in the United States and is immediately established as a powerful antiinfective agent.[21] United States
1937 Introduction The first effective antimicrobials (sulfonamides) are introduced.[22]
1938 Introduction Sulfapyridine is introduced for clinical use for the treatment of pneumococcic pneumonia.[23][24] Today it is used to help control dermatitis herpetiformis (Duhring's disease), a skin problem.[25]
1939 Isolation Microbiologist René Dubos manages to isolate an antibacterial substance and names it tyrothricin.[17]
1939 Introduction Gramicidin A is discovered from the soil bacterium bacillus brevis, and becomes the first clinically useful topical antibiotic.[26][27][28]
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.[29][30][31]
1939 Introduction Sulfonamide antibiotic sulfacetamide is first reported in the treatment of diseases of the eye.[32][33] Today it is used to treat bacterial eye infections, such as conjunctivitis.[34]
1940 Introduction Sulfonamide antibiotic sulfamethizole is introduced and marketed as a single compound for the treatment of urinary tract infections.[35][36][37]
1941 Introduction β-lactam antibiotics enter initial clinical trials. In time, they would become the most widely produced and used antibacterial drugs in the world.[38][39] β-lactam antibiotics now the most economically important of all the groups of antimicrobials.[40]
1941 Introduction Penicillin is introduced for medical use.[41][20] Just before the introduction of penicillin, the mortality rate from Staphylococcus aureus infections that had reached the blood stream was reported to be 80%.[41]
1942 Introduction Sulfadimidine is introduced for the treatment of bacterial infections.[42][43][44][45]
1942 Resistance Penicillin resistant bacteria are first detected, about one year after the introduction of penicillin.[41]
1942 Isolation Gramicidin S, the first peptide antibiotic, is isolated by Gauze and Brazhnikova.[46][47][48]
1943 Introduction American biochemists Selman Waksman, Albert Schatz, and Elizabeth Bugie discover antibiotic streptomycin, the first aminoglycoside. It is the first antibiotic effective against tuberculosis.[5][49][50][51][20] United States
1943 Introduction Sulfamerazine is synthesized by American chemists.[52] The drug is today used as an antibacterial agent.[53][54][55][56] United States
1943 Production Penicillin is mass produced and used heavily to treat Allied troops fighting in Europe during World War II.[2]
1943 Isolation Bacitracin is first isolated.[57][58] The drug is used to prevent minor skin infections caused by small cuts, scrapes, or burns.[59]
1945 Discovery The cephalosporins are discovered from a fungus, Cephalosporium acremonium, in seawater samples near a sewage outfall in Sardinia.[20][60][61][62] Italy
1947 Isolation 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.[63][64][65][66]
1947 Isolation American plant physiologist Benjamin Minge Duggar isolates chlortetracycline from a Missouri River mud sample. It is the first tetracycline introduced.[67][68][69][70] United States
1947 Isolation The polymyxin family of antibiotics is discovered, with polymyxin B being the first isolated from bacterium paenibacillus polymyxa.[5][71][72]
1947 Introduction Drug class Nitrofuran is introduced.[38] 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.[73]
1948 Introduction Mafenide –a sulfonamide-type antibiotic, is approved by the United States FDA.[74][75]
1949 Isolation 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.[76][77][78] United States
1949 Scientific development British chemist Dorothy Hodgkin reveals the complete structure of molecular penicillin, using the X-ray crystallography.[22] United Kingdom
1950 Introduction Oxytetracycline comes into commercial use.[58][79][80] Since then, this antibiotic would be used widely in human and veterinary medicine.[81]
1950 Resistance Resistance against chloramphenicol is observed.[82]
1952 Introduction Lincosamides are introduced.[38] 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.[83]
1952 Introduction Antibiotic thiamphenicol is first synthesized.[84] It is a broad spectrum antibiotic with good activity against Gram negative and anaerobic bacteria.[85]
1952 Introduction 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.[86][87][88] Erythromycin is the first macrolide antibiotic.[89] United States
1952 Introduction 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.[38]
1953 Introduction 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.[90][5] United Kingdom
1953 Resistance Macrolide resistance is observed.[38]
1954 Introduction Benzathine penicillin is established as a method for the treatment of syphilis.[91]
1954 Discovery Antibiotic cycloserine is discovered. It is used for the treatment of tuberculosis.[92][93]
1955 Introduction Macrolide antibiotic spiramycin is first introduced into the French market.[94] Spiramycin is used to treat various infections.[95] France
1956 Isolation 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.[20][96][97][98] United States
1956 Resistance Resistance against erythromycin is observed.[82]
1957 Introduction Kanamycin is discovered. It is used to treat severe bacterial infections and tuberculosis.[58]
1957 Introduction Ansamycins are introduced. These bacterial secondary metabolites show antimicrobial activity against many Gram-positive and some Gram-negative bacteria.[38]
1959 Introduction Colistin becomes available for treating infections caused by gram-negative bacteria.[5]
1959 Introduction Nitroimidazoles are introduced. They are effective bactericidal agents against anaerobes and protozoa.[38]
1960 Introduction In an attempt to defeat penicillin-resistant strains, scientists develop methicillin, a different antibiotic in the penicillin class.[2][82]
1960 Introduction 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.[99][100][101]
1961 Resistance Methicillin resistance is first reported.[41][82][38]
1961 Introduction Antibiotic ampicillin is introduced. Within a short time it would become the drug of choice for treatment of Hemophilus influenzae meningitis.[102][103][104][20]
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 Discovery Spectinomycin is first reported. Today it is used for the treatment of gonorrhea infections.[105][58]
1961 Discovery Ethambutol is discovered. The medication is primarily used for the treatment of tuberculosis.[106][107][108]
1962 The fusidic acid is introduced into clinical practice.[109] The antibiotic is prescribed for skin infections caused by staphylococcal bacteria.[110]
1962 Introduction Quinolones are discovered accidentally, as a byproduct of some research on the antimalarial drug chloroquine.[5][38]
1963 Isolation Weinstein and his colleagues from the Schering Corporation describe the first isolation of the gentamicin complex.[20][111][112][113] United States
1963 Introduction Gentamicin is discovered. It is used to treat several types of bacterial infections.[58]
1963 Resistance Gram-negative bacterium acinetobacter baumannii becomes an antibiotic resistant pathogen.[41]
1965 Introduction Antibiotic Cloxacillin synthesized. Today it is useful for the treatment of a number of bacterial infections,[114] including impetigo, cellulitis, pneumonia, septic arthritis, and otitis externa.[114] It is used by mouth and by injection.[114].[115][116][117]
1966 Resistance Nalidixic acid resistance is observed.[38]
1966 Synthesis Antibiotic doxycycline is synthesized.[118][119][120] Today it is used for bacterial pneumonia, acne, {{w|chlamydia infection}s, early Lyme disease, cholera and syphilis.[121]
1966 Resistance Resistance against cephalotin is observed.[82]
1967 Introduction Clindamycin is first produced. Today it is used for the treatment of a number of bacterial infections.[58]
1968 Introduction Antibiotic rifampicin is introduced for clinical use.[122][123][124] The introduction of rifampicin would greatly shorten the duration of tuberculosis chemotherapy.[125] Italy
1968 Resistance Tetracycline resistance is observed.[38][38]
1968 Introduction Trimethoprim is introduced. It is used mainly in the treatment of bladder infections.[38]
1969 Discovery 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.[126][127][128] Spain
1970 Introduction Non-toxic semi-synthetic acid-resistant isoxazolyl penicillin flucloxacillin is introduced into clinical practice.[117][129]
1971 Introduction Aminoglycoside antibiotic Tobramycin is discovered. It is used to treat various types of bacterial infections, particularly Gram-negative infections.[58]
1972 Isolation Extracellular broad spectrum beta-lactam antibiotic cephamycin C is first isolated.[130][58]
1972 Introduction Antibiotic minocycline is discovered.[118][119][120] It has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne.[131]
1973 Introduction Bactericidal antibiotic Carbenicillin is discovered. It belongs to the carboxypenicillin subgroup of the penicillins.[132] Carbenicillin has bactericidal and beta-lactamase resistant activity.[133]
1974 Introduction Antibiotic trimethoprim/sulfamethoxazole is commercially released.[134][20]
1974 Introduction Cotrimoxazole is introduced.[58] 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.[135]
1976 Introduction The Bristol-Banyu research institute in Japan publishes the discovery of antibiotic amikacin.[20][58][136] Amikacin is active against a broad spectrum of Gram-negative organisms, including pseudomonas, Escherichia coli and some Gram-positive organisms, like Staphylococcus aureus.[137] 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 Introduction Cefoxitin is introduced as an early cephamycin.[132][138] It is synthesized in order to create an antibiotic with a broader spectrum.[139]
1978 Discovery The teicoplanin family of glycopeptides is discovered.[140] Teicoplanin is used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis.[141]
1979 Introduction Eli Lilly patents antibiotic cefaclor.[142][143][144] 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.[38]
1981 Discovery 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.[145]
1983 Resistance Extended-spectrum-beta-lactamase resistance is observed.[38]
1984 Introduction amoxicillin clavulanate is introduced.[58] It is specifically used for otitis media, strep throat, pneumonia, cellulitis, urinary tract infections, animal bites, and tuberculosis.[146]
1985 Introduction Researchers at Eli Lilly and Company discover antibiotic daptomycin.[147][148][149] United States
1985 Introduction Carbapenems are introduced.[82] These are commonly used for the treatment of severe or high-risk bacterial infections.
1986 Resistance Vancomycin-resistant enterococcus is reported.[82][38]
1987 Introduction Antibiotic imipenem/cilastin is introduced.[20] It is useful for the treatment of pneumonia, sepsis, endocarditis, joint infections, intra-abdominal infections, and urinary tract infections.[150]
1987 Introduction Highly potent fluoroquinolones are introduced.[22] These are used to treat a variety of illnesses such as respiratory and urinary tract infections.[151]
1987 Resistance Resistance against cephalosporins is observed.[82]
1987 Resistance Resistance against carbapenems is observed.[82]
1990s Resistance Fluorochinolone resistance is observed.[38]
1993 Introduction Antibiotic azithromycin is introduced.[20] 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.[152]
1993 Introduction Antibiotic clarithromycin is introduced.[20] It is used to prevent and treat certain infections caused by bacteria.[153]
1994 Introduction 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.[154]
1997 Resistance Vancomycin-resistant staphyloccocus is reported.[38]
1999 Introduction Antibiotic quinupristin/dalfopristin is introduced.[20] The combination is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium.
2000 Introduction Oxazolidinones are introduced.[38] 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.[155]
2000 Introduction Antibiotic linezolid is introduced for the treatment of infections caused by gram-positive bacteria that are resistant to other antibiotics.[20][82] An oxazolidinone antibiotic, linezolid represents the first principally new antibiotic platform that has entered medical practice in more than 30 years.[156][38]
2001 Introduction Antibiotic telithromycin is introduced in the European Union.[157][158][159] It is used to treat certain types of pneumonia.[160]
2001 Introduction Broader-spectrum fluoroquinolones are introduced.[132]
2002 Resistance Resistance against linezolid is observed.[82]
2002 Introduction The United States Food and Drug Administration approves cefditoren, pivoxil and ertapenem. [161][58]
2002 Resistance Vancomycin-resistant staphylococcus aureus is reported.[38]
2003 Introduction Lipopeptides are introduced as antibiotics.[38]
2003 Introduction Daptomycin is introduced for treatment of systemic and life-threatening infections caused by Gram-positive organisms.[20]
2004 Introduction Telythromicin is introduced.[58] It is used to treat certain types of pneumonia.[162]
2005 Introduction Antibiotic tigecycline is introduced for the treatment of skin and skin structure infections and intraabdominal infections.[163][164][165]
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 Introduction The United States Food and Drug Administration approves fidaxomicin for treatment of clostridium Difficile Infection.[166][167] 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 Introduction The United States Food and Drug Administration approves bedaquiline for the treatment of multidrug-resistant tuberculosis.[168][169] United States
2013 Introduction The United States Food and Drug Administration approves telavancin for the treatment of hospital-acquired pneumonia caused by susceptible staphylococcus aureus.[170][171][172] 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 Introduction 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.[173] United States
2015 Policy American fast food company McDonald's announces that it would phase out all meat sources that contain antibiotics.[2]
2015 Introduction Ceftazidime/avibactam is introduced for use in the United States.[174][175][176] The combination is used for treatment against certain multidrug-resistant Gram-negative infections. United States
2018 Introduction The discovery of malacidins is published.[177] The novel antibiotic can work against many of the multidrug-resistant bacterial strains.[178]

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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. ↑ Tierno, Philip M. The Secret Life of Germs: What They Are, Why We Need Them, and How We Can Protect Ourselves Against Them. 
  8. ↑ Williams, Elizabeth S.; Barker, Ian K. Infectious Diseases of Wild Mammals. 
  9. ↑ Newell-McGloughlin, Martina; Re, Edward. The Evolution of Biotechnology: From Natufians to Nanotechnology. 
  10. ↑ 10.0 10.1 Newell-McGloughlin, Martina; Re, Edward. The Evolution of Biotechnology: From Natufians to Nanotechnology. 
  11. ↑ Zhang, Yawei. Encyclopedia of Global Health, Volume 1. 
  12. ↑ Myers, Richard L. The 100 Most Important Chemical Compounds: A Reference Guide. 
  13. ↑ Manning, Shannon D.; Alcamo, I. Edward; Heymann, David L. Escherichia Coli Infections. 
  14. ↑ SWATHY, S; ARYA, US. "ANTIBIOTIC USAGE IN PEDIATRICS" (PDF). INTERNATIONAL JOURNAL FOR INNOVATIVE RESEARCH IN MULTIDISCIPLINARY FIELD. 
  15. ↑ Thomas, Gareth. Medicinal Chemistry: An Introduction. 
  16. ↑ "Neosalvarsan". sciencedirect.com. Retrieved 1 April 2018. 
  17. ↑ 17.0 17.1 "René Dubos". britannica.com. Retrieved 30 March 2018. 
  18. ↑ Ravina, Enrique. The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. 
  19. ↑ Savona-Ventura, Charles. Contemporary Medicine in Malta [1798-1979]. 
  20. ↑ 20.00 20.01 20.02 20.03 20.04 20.05 20.06 20.07 20.08 20.09 20.10 20.11 20.12 20.13 20.14 Torok, Estee; Moran, Ed; Cooke, Fiona. Oxford Handbook of Infectious Diseases and Microbiology. 
  21. ↑ HUGHES, RAYMOND P. "THE USE OF SULFANILAMIDE IN DERMATOLOGY". doi:10.1001/archderm.1940.01490130037006. 
  22. ↑ 22.0 22.1 22.2 Davies, Julian; Davies, Dorothy. "Origins and Evolution of Antibiotic Resistance" (PDF). doi:10.1128/MMBR.00016-10. 
  23. ↑ "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". karger.com. Retrieved 1 April 2018. 
  24. ↑ DETWEILER, H. K.; KINSEY, H. I.; HURST, W. "TREATMENT OF PNEUMONIA WITH SULFAPYRIDINE". 
  25. ↑ "Sulfapyridine (Oral Route)". mayoclinic.org. Retrieved 2 May 2018. 
  26. ↑ Bhattacharjee, Mrinal K. Chemistry of Antibiotics and Related Drugs. 
  27. ↑ Mouritsen, Ole G. Life - As a Matter of Fat: The Emerging Science of Lipidomics. 
  28. ↑ Current Topics in Membranes and Transport, Volume 33. 
  29. ↑ Stadler, Marc; Dersch, Petra. How to Overcome the Antibiotic Crisis: Facts, Challenges, Technologies and Future Perspectives. 
  30. ↑ Persson, Sheryl. Smallpox, Syphilis and Salvation: Medical Breakthroughs that Changed the World. 
  31. ↑ Smallman-Raynor,, Matthew; Cliff, Andrew. Atlas of Epidemic Britain: A Twentieth Century Picture. 
  32. ↑ DUEMLING, WERNER W. "SODIUM SULFACETAMIDE IN TOPICAL THERAPY". 
  33. ↑ DUEMLING, WERNER W. "SODIUM SULFACETAMIDE IN TOPICAL THERAPY". doi:10.1001/archderm.1954.01540130077007. 
  34. ↑ "Sulfacetamide Sodium Drops". webmd.com. Retrieved 2 May 2018. 
  35. ↑ Vree, T.B. "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". doi:10.1159/000414195. 
  36. ↑ Vree, Tom B.; Aaron, Yechiel; Karger, Hekster S. Antibiotics and Chemotherapy, Volume 37. 
  37. ↑ The New Yorker, Volume 45, Part 2. 
  38. ↑ 38.00 38.01 38.02 38.03 38.04 38.05 38.06 38.07 38.08 38.09 38.10 38.11 38.12 38.13 38.14 38.15 38.16 38.17 38.18 38.19 38.20 38.21 "Antibiotics armageddon?". mega.online. Retrieved 31 March 2018. 
  39. ↑ "Beta lactam antibiotics". slideshare.net. Retrieved 2 May 2018. 
  40. ↑ "β-Lactam Antibiotics". sciencenutshell.com. Retrieved 2 May 2018. 
  41. ↑ 41.0 41.1 41.2 41.3 41.4 Landecker, Hannah. "Antibiotic Resistance and the Biology of History". 
  42. ↑ [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. 
  43. ↑ "Clinical Pharmacokinetics of Sulfonamides and Their Metabolites". karger.com. Retrieved 1 April 2018. 
  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. ↑ Vree, Tom B.; Hekster, Yechiel Aaron. Antibiotics and Chemotherapy, Volume 37. 
  46. ↑ 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▿". 
  47. ↑ GAUSE, G. F.; BRAZHNIKOVA, M. G. "Gramicidin S and its use in the Treatment of Infected Wounds". Nature. doi:10.1038/154703a0. 
  48. ↑ Korzybski, Tadeusz; Kowszyk-Gindifer, Zuzanna; Kurylowicz, Wlodzimierz. Antibiotics: Origin, Nature and Properties. 
  49. ↑ Lorian, Victor. Antibiotics in Laboratory Medicine. 
  50. ↑ Morabia, Alfredo. Enigmas of Health and Disease: How Epidemiology Helps Unravel Scientific Mysteries. 
  51. ↑ 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. 
  52. ↑ Boothe, Russell G. "Comparison of sulfathiazole with sulfamerazine in extraction and impaction". 
  53. ↑ "Sulfamerazine". pubchem.ncbi.nlm.nih.gov. Retrieved 2 May 2018. 
  54. ↑ Santo Tomas Journal of Medicine, Volume 3. University of Santo Tomas, College of Medicine. 
  55. ↑ Biennial Report. North Dakota. State Dept. of Health. 
  56. ↑ Nelson loose-leaf living medicine, Volume 8. T. Nelson & Sons. 
  57. ↑ "Bacitracin A". pubchem.ncbi.nlm.nih.gov. Retrieved 2 May 2018. 
  58. ↑ 58.00 58.01 58.02 58.03 58.04 58.05 58.06 58.07 58.08 58.09 58.10 58.11 58.12 "The Golden Age of Antibacterials". amrls.cvm.msu.edu. Retrieved 31 March 2018. 
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  88. ↑ Nightingale; Mur. Antimicrobial Pharmacodynamics in Theory and Clinical Practice, Second Edition. 
  89. ↑ Roberts, Marilyn C.; Sutcliffe, Joyce; Courvalin, Patrice; Jensen, Lars Bogo; Rood, Julian; Seppala, Helena. "Nomenclature for Macrolide and Macrolide-Lincosamide-Streptogramin B Resistance Determinants". 
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  91. ↑ Ellis, Albert; Abarbanel, Albert. The Encyclopædia of Sexual Behaviour, Volume 2. 
  92. ↑ Greenwood, David. Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. 
  93. ↑ Cordes, Eugene H. Hallelujah Moments: Tales of Drug Discovery. 
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  96. ↑ Staphylococci in Human Disease (Kent B. Crossley, Kimberly K. Jefferson, Gordon L. Archer, Vance G. Fowler ed.). 
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  99. ↑ Olson Robbie, Marilyn; Sweet, Richard L. "Metronidazole use in obstetrics and gynecology: A review". American Journal of Obstetrics and Gynecology. 
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  102. ↑ Atta-ur-Rahman. Studies in Natural Products Chemistry, Volume 56. 
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  104. ↑ Fifty Years of Antimicrobials: Past Perspectives and Future Trends. Society for General Microbiology. Symposium. 
  105. ↑ Bhattacharjee, Mrinal K. Chemistry of Antibiotics and Related Drugs. 
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  121. ↑ "Streptomyces aureofaciens". sciencedirect.com. Retrieved 12 May 2018. 
  122. ↑ Rahman, Atta -ur-; Choudhary, M. Iqbal. Frontiers in Anti-Infective Drug Discovery, Volume 6. 
  123. ↑ Kucers' The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition - Three Volume Set (y M. Lindsay Grayson, Sara E. Cosgrove, Suzanne Crowe, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson ed.). 
  124. ↑ Mann, R.D. Modern Drug use: An Enquiry on Historical Principles. 
  125. ↑ Campbell, Elizabeth A.; Korzheva, Nataliya; Mustaev, Arkady; Murakami, Katsuhiko; Nair, Satish; Goldfarb, Alex; Darst, Seth A. "Structural Mechanism for Rifampicin Inhibition of Bacterial RNA Polymerase". 
  126. ↑ Michalopoulos, Argyris S.; Livaditis, Ioannis G.; Gougoutas, Vassilios. "The revival of fosfomycin". International Journal of Infectious Diseases. 
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  133. ↑ "Carbenicillin". pubchem.ncbi.nlm.nih.gov. Retrieved 12 May 2018. 
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  135. ↑ "Co-trimoxazole". medlineplus.gov. Retrieved 12 May 2018. 
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  143. ↑ Amann, Edmund; Cantwell, John. Innovative Firms in Emerging Market Countries. 
  144. ↑ Meléndez-Ortiz,, Ricardo; Roffe, Pedro. Intellectual Property and Sustainable Development: Development Agendas in a Changing World. 
  145. ↑ "Ciprofloxacin (Cipro®)". emedexpert.com. Retrieved 12 May 2018. 
  146. ↑ "Amoxicillin and Clavulanate Potassium". The American Society of Health-System Pharmacists. Archived from the original on 29 November 2016. Retrieved 12 May 2018. 
  147. ↑ Current Medical Research and Opinion, Volume 22, Issues 9-12. Clayton-Wray Publications Limited, 2006. 
  148. ↑ Rybak, M. J. "The efficacy and safety of daptomycin: first in a new class of antibiotics for Gram‐positive bacteria". 
  149. ↑ Beiras-Fernandez, Andres; Ferdinand Vogt, Ferdinand Vogt; Sodian, Ralf; Weis, Florian. "Daptomycin: a novel lipopeptide antibiotic against Gram-positive pathogens". PMC 3108743Freely accessible. PMID 21694898. doi:10.2147/IDR.S6961. 
  150. ↑ "Imipenem and Cilastatin". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 12 May 2018. 
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  152. ↑ "Azithromycin". medlineplus.gov. Retrieved 12 May 2018. 
  153. ↑ "Clarithromycin, Oral Tablet". healthline.com. Retrieved 12 May 2018. 
  154. ↑ Endimiani, Andrea; Perez, Federico; Bonomo, Robert A. "Cefepime: a reappraisal in an era of increasing antimicrobial resistance". PMID 19053894. doi:10.1586/14787210.6.6.805. Retrieved 13 May 2018. 
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  157. ↑ 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.). 
  158. ↑ Alex, Alexander; Harris, C. John; Smith, Dennis A. Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward. 
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  177. ↑ "A new antibiotic Malacidin from soil kills resistant bacteria". news-medical.net. Retrieved 2 April 2018. 
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