Difference between revisions of "Timeline of antibiotics"

Revision as of 11:00, 2 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

Note: The event type "introduction" could mean the discovery of the drug, its approval for use or its commercial release.

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 are introduced.^[38]
1941	Introduction	Penicillin is introduced for medical use.^[39]^[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%.^[39]
1942	Introduction	Sulfadimidine is introduced as a single compound.^[40]^[41]^[42]
1942	Resistance	Penicillin resistant bacteria are first detected, about one year after the introduction of penicillin.^[39]
1942	Isolation	Gramicidin S, the first peptide antibiotic, is isolated by Gauze and Brazhnikova.^[43]^[44]^[45]
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]^[46]^[47]^[48]^[20]	United States
1943	Introduction	Sulfamerazine is introduced.^[49]^[50]^[51]
1943	Production	Penicillin is mass produced and used heavily to treat Allied troops fighting in Europe during World War II.^[2]
1943	Introduction	Bacitracin is discovered.^[52]
1945	Introduction	The cephalosporins are discovered from a fungus, Cephalosporium acremonium, in seawater samples near a sewage outfall in Sardinia.^[20]^[53]^[54]^[55]	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.^[56]^[57]^[58]^[59]
1947	Isolation	American plant physiologist Benjamin Minge Duggar isolates chlortetracycline from a Missouri River mud sample. It is the first tetracycline introduced.^[60]^[61]^[62]^[63]	United States
1947	Isolation	Antibiotic polymyxin family of antibiotics is discovered, with polymyxin B being the first isolated from bavterium paenibacillus polymyxa.^[5]^[64]^[65]
1947	Introduction	Nitrofuran is introduced.^[38]
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.^[66]^[67]^[68]	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.^[52]^[69]^[70]
1950	Resistance	Resistance against chloramphenicol is observed.^[71]
1952	Introduction	Macrolides are introduced.^[38]
1952	Introduction	Lincosamides are introduced.^[38]
1952	Introduction	Antibiotic thiamphenicol is first synthesized.^[72]
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.^[73]^[74]^[75]	United States
1952	Introduction	Streptoramins are introduced.^[38]
1953	Introduction	Oxford University scientists discover antibiotic cephalosporin C.^[5]	United Kingdom
1953	Resistance	Macrolide resistance is observed.^[38]
1954	Introduction	Benzathine penicillin is established as a method for the treatment of syphilis.^[76]
1955	Introduction	Macrolide antibiotic spiramycin is first introduced into the French market.^[77]	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]^[78]^[79]^[80]	United States
1956	Introduction	Glycopeptides are introduced.^[38]
1956	Resistance	Resistance against erythromycin is observed.^[71]
1957	Introduction	Kanamycin is discovered. It is used to treat severe bacterial infections and tuberculosis.^[52]
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]^[71]
1961	Resistance	Methicillin resistance is first reported.^[39]^[71]^[38]
1961	Introduction	Antibiotic ampicillin is introduced. Within a short time it would become the drug of choice for treatment of Hemophilus influenzae meningitis.^[81]^[82]^[83]^[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	Introduction	Spectinomycin is first reported.^[52]
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]^[84]^[85]^[86]	United States
1963	Introduction	Gentamicin is discovered. It is used to treat several types of bacterial infections.^[52]
1963	Resistance	Gram-negative bacterium acinetobacter baumannii becomes an antibiotic resistant pathogen.^[39]
1965	Introduction	Dicloxacillin is synthesized by Bayer.^[87]^[88]^[89]
1966	Resistance	Nalidixic acid resistance is observed.^[38]
1966	Introduction	Antibiotic doxycycline is introduced.^[90]^[91]^[92]^[20]
1966	Resistance	Resistance against cephalotin is observed.^[71]
1967	Introduction	Clindamycin is first produced. It is used for the treatment of a number of bacterial infections.^[52]
1968	Introduction	Antibiotic rifampicin is introduced for clinical use.^[93]^[94]^[95]	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]
1970	Introduction	Non-toxic semi-synthetic acid-resistant isoxazolyl penicillin flucloxacillin is introduced into clinical practice.^[89]^[96]
1971	Introduction	Aminoglycoside antibiotic Tobramycin is discovered. It is used to treat various types of bacterial infections, particularly Gram-negative infections.^[52]
1972	Isolation	Extracellular broad spectrum beta-lactam antibiotic cephamycin C is first isolated.^[97]^[52]
1972	Introduction	Antibiotic minocycline is discovered.^[90]^[91]^[92]
1973	Introduction	Bactericidal antibiotic Carbenicillin is discovered. It belongs to the carboxypenicillin subgroup of the penicillins.^[98]
1974	Introduction	Antibiotic trimethoprim/sulfamethoxazole is commercially released.^[99]^[20]
1974	Introduction	Cotrimoxazole is introduced.^[52]
1976	Introduction	Antibiotic amikacin is introduced.^[20]
1976	Resistance	Tufts University researcher Stuart B. Levy becomes one of the first to identify antibiotic resistance due to their use in animals.^[2]
1976	Introduction	Amikacin is introduced.^[52]
1978	Introduction	Cefoxitin is introduced.^[98]^[100]
1979	Introduction	Eli Lilly patents antibiotic cefaclor.^[101]^[102]^[103]	United States
1981	Resistance	AmpC beta-lactamase resistance is observed.^[38]
1983	Resistance	Extended-spectrum-beta-lactamase resistance is observed.^[38]
1984	Introduction	Antibiotic ampicillin/clavulanate is introduced.^[20]
1984	Introduction	amoxicillin clavulanate is introduced.^[52]
1985	Introduction	Researchers at Eli Lilly and Company discover antibiotic daptomycin.^[104]^[105]^[106]	United States
1985	Introduction	Carbapenems are introduced.^[71]
1986	Resistance	Vancomycin-resistant enterococcus is reported.^[71]^[38]
1987	Introduction	Antibiotic imipenem/cilastin is introduced.^[20]
1987	Introduction	Highly potent fluoroquinolones are introduced.^[22]
1987	Introduction	Antibiotic ciprofloxacin is introduced.^[20]^[107]^[108]
1987	Resistance	Resistance against cephalosporins is observed.^[71]
1987	Resistance	Resistance against carbapenems is observed.^[71]
1990s	Resistance	Fluorochinolone resistance is observed.^[38]
1993	Introduction	Antibiotics azithromycin and clarithromycin are introduced.^[20]
1997	Resistance	Vancomycin-resistant staphyloccocus is reported.^[38]
1999	Introduction	Antibiotic quinupristin/dalfopristin is introduced.^[20]
2000	Introduction	Oxazolidinones are introduced.^[38]
2000	Introduction	Antibiotic linezolid is introduced for the treatment of infections caused by gram-positive bacteria that are resistant to other antibiotics.^[20]^[71]
2001	Introduction	Antibiotic telithromycin is introduced in the European Union.^[109]^[110]^[111]
2001	Introduction	Broader-spectrum fluoroquinolones are introduced.^[98]
2002	Resistance	Resistance against linezolid is observed.^[71]
2002	Introduction	The United States Food and Drug Administration approves cefditoren, pivoxil and ertapenem. ^[112]^[52]
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.^[52]
2005	Introduction	Antibiotic tigecycline is introduced for the treatment of skin and skin structure infections and intraabdominal infections.^[113]^[114]^[115]
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.^[116]^[117]	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.^[118]^[119]	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.^[120]^[121]^[122]	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.^[123]	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.^[124]^[125]^[126]	United States
2018	Introduction	The discovery of malacidins is published.^[127]

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References

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↑ Andriole, Vincent T. The Quinolones.
↑ Aronson, Jeffrey K. Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions.
↑ 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.).
↑ Alex, Alexander; Harris, C. John; Smith, Dennis A. Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward.
↑ Hugo and Russell's Pharmaceutical Microbiology (Stephen P. Denyer, Norman A. Hodges, Sean P. Gorman, Brendan F. Gilmore ed.).
↑ Zinner, SH. "The search for new antimicrobials: why we need new options.". PMID 16307503. doi:10.1586/14787210.3.6.907.
↑ Low-dose antibiotics: current status and outlook for the future (Robert Paul Hunter, Carlos F Amábile-Cuevas, Jun Lin, Joshua D Nosanchuk, Rustam Aminov ed.).
↑ Vincent, Jean-Louis; Abraham, Edward; Kochanek, Patrick; Moore, Frederick A.; Fink, Mitchell P. Textbook of Critical Care E-Book.
↑ Trauma: Critical Care (William C. Wilson, Christopher M. Grande, David B. Hoyt ed.).
↑ Richards, Jeremy B.; Stapleton, Renee D. Non-Pulmonary Complications of Critical Care: A Clinical Guide.
↑ Bope, Edward T.; Kellerman, Rick D. Conn's Current Therapy 2017 E-Book.
↑ Kurreck,, Jens; Stein, Aaron. Molecular Medicine: An Introduction.
↑ Villa,, Tomas G.; Vinas, Miguel. New Weapons to Control Bacterial Growth.
↑ Mandell, Gerald L. Principles and Practice of Infectious Diseases.
↑ Bennett, John E.; Dolin, Raphael; Blaser, Martin J. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases E-Book.
↑ Villa, Tomas G.; Vinas, Miguel. New Weapons to Control Bacterial Growth.
↑ Alex, Alexander; Harris, C. John; Smith, Dennis A. Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward.
↑ Stanbury, Peter F; Whitaker, Allan; Hall, Stephen J. Principles of Fermentation Technology.
↑ Wanger, Audrey; Chavez, Violeta; Huang, Richard; Wahed, Amer; Dasgupta, Amitava; Actor, Jeffrey K. Microbiology and Molecular Diagnosis in Pathology: A Comprehensive Review for Board Preparation, Certification and Clinical Practice.
↑ Chandrasekar, Pranatharthi H. Infections in the Immunosuppressed Patient: An Illustrated Case-Based Approach.
↑ "A new antibiotic Malacidin from soil kills resistant bacteria". news-medical.net. Retrieved 2 April 2018.

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@@ Line 26: / Line 26: @@
 | 1887 || Scientific development || German bacteriologist {{w|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.<ref>{{cite book|last1=Newell-McGloughlin|first1=Martina|last2=Re|first2=Edward|title=The Evolution of Biotechnology: From Natufians to Nanotechnology|url=https://books.google.com.ar/books?id=U27lbghWOfsC&pg=PA23&dq=%22in+1887%22+%22streptococcus+%22+%22emmerich%22+%22cholera%22&hl=en&sa=X&ved=0ahUKEwj_zbvmz6PaAhVJvZAKHY3TCsIQ6AEIKDAA#v=onepage&q=%22in%201887%22%20%22streptococcus%20%22%20%22emmerich%22%20%22cholera%22&f=false}}</ref> ||
 |-
-| 1888 || Scientific development || German scientist E. de Freudenreich manages to isolate an actual product from a bacterium that had antibacterial properties.<ref name="The Evolution of Biotechnology: From Natufians to Nanotechnology">{{cite book|last1=Newell-McGloughlin|first1=Martina|last2=Re|first2=Edward|title=The Evolution of Biotechnology: From Natufians to Nanotechnology|url=https://books.google.com.ar/books?id=U27lbghWOfsC&pg=PA23&lpg=PA23&dq=E.+de+Freudenreich&source=bl&ots=69HqimydSe&sig=021aY8DvwKO8_TlY5ZfeEenZ8d4&hl=en&sa=X&ved=0ahUKEwjtvvWs5pTaAhXDGJAKHb5WB5AQ6AEIWTAK#v=onepage&q=E.%20de%20Freudenreich&f=false}}</ref> ||
+| 1888 || Isolation || German scientist E. de Freudenreich manages to isolate an actual product from a bacterium that had antibacterial properties.<ref name="The Evolution of Biotechnology: From Natufians to Nanotechnology">{{cite book|last1=Newell-McGloughlin|first1=Martina|last2=Re|first2=Edward|title=The Evolution of Biotechnology: From Natufians to Nanotechnology|url=https://books.google.com.ar/books?id=U27lbghWOfsC&pg=PA23&lpg=PA23&dq=E.+de+Freudenreich&source=bl&ots=69HqimydSe&sig=021aY8DvwKO8_TlY5ZfeEenZ8d4&hl=en&sa=X&ved=0ahUKEwjtvvWs5pTaAhXDGJAKHb5WB5AQ6AEIWTAK#v=onepage&q=E.%20de%20Freudenreich&f=false}}</ref> ||
 |-
 | 1896 || Scientific development || French medical student {{w|Ernest Duchesne}} originally discovers the antibiotic properties of {{w|Penicillium}}.<ref>{{cite book|last1=Zhang|first1=Yawei|title=Encyclopedia of Global Health, Volume 1|url=https://books.google.com.ar/books?id=1_XIbBRvD0gC&pg=PA145&dq=%22in+1896%22+%22Ernest+Duchesne%22&hl=en&sa=X&ved=0ahUKEwjo15Pi75TaAhUDCpAKHVFPDLQQ6AEIKDAA#v=onepage&q=%22in%201896%22%20%22Ernest%20Duchesne%22&f=false}}</ref><ref>{{cite book|last1=Myers|first1=Richard L.|title=The 100 Most Important Chemical Compounds: A Reference Guide|url=https://books.google.com.ar/books?id=nKtzCgAAQBAJ&pg=PA210&dq=%22in+1896%22+%22Ernest+Duchesne%22&hl=en&sa=X&ved=0ahUKEwjo15Pi75TaAhUDCpAKHVFPDLQQ6AEIOTAD#v=onepage&q=%22in%201896%22%20%22Ernest%20Duchesne%22&f=false}}</ref><ref>{{cite book|last1=Manning|first1=Shannon D.|last2=Alcamo|first2=I. Edward|last3=Heymann|first3=David L.|title=Escherichia Coli Infections|url=https://books.google.com.ar/books?id=TFkzNocHde4C&pg=PA64&dq=%22in+1896%22+%22Ernest+Duchesne%22&hl=en&sa=X&ved=0ahUKEwjo15Pi75TaAhUDCpAKHVFPDLQQ6AEIMTAC#v=onepage&q=%22in%201896%22%20%22Ernest%20Duchesne%22&f=false}}</ref> ||
@@ Line 38: / Line 38: @@
 | 1928 || Introduction || Scottish microbiologist {{w|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 {{w|staphylococcus}}, which causes boils, sore throats and abscesses. Flemming discovers killed baceria in one dish contaning a blob of mold on it.<ref name="The Evolution of Biotechnology: From Natufians to Nanotechnology"/><ref name="Ten important moments in the history of antibiotic discovery"/>|| {{w|United Kingdom}}
 |-
-| 1930 || || French-born American microbiologist {{w|René Dubos}} isolates from a soil microorganism an enzyme that can decompose part of the bacillum that causes lobar pneumonia in humans.<ref name="René Dubos">{{cite web|title=René Dubos|url=https://www.britannica.com/biography/Rene-Dubos|website=britannica.com|accessdate=30 March 2018}}</ref> ||
+| 1930 || Isolation || French-born American microbiologist {{w|René Dubos}} isolates from a soil microorganism an enzyme that can decompose part of the bacillum that causes lobar pneumonia in humans.<ref name="René Dubos">{{cite web|title=René Dubos|url=https://www.britannica.com/biography/Rene-Dubos|website=britannica.com|accessdate=30 March 2018}}</ref> ||
 |-
 | 1932 || Introduction || German pathologist {{w|Gerhard Domagk}} develops {{w|prontosil}}, the first sulphonamide microbial.<ref>{{cite book|last1=Ravina|first1=Enrique|title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs|url=https://books.google.com.ar/books?id=iDNy0XxGqT8C&pg=PA48&dq=%22in+1932%22+%22prontosil%22&hl=en&sa=X&ved=0ahUKEwjLxOHfn4PaAhVEGZAKHWKXB_gQ6AEILzAB#v=onepage&q=%22in%201932%22%20%22prontosil%22&f=false}}</ref><ref>{{cite book|last1=Savona-Ventura|first1=Charles|title=Contemporary Medicine in Malta [1798-1979]|url=https://books.google.com.ar/books?id=eMgkDAAAQBAJ&pg=PA465&dq=%22in+1932%22+%22prontosil%22&hl=en&sa=X&ved=0ahUKEwjLxOHfn4PaAhVEGZAKHWKXB_gQ6AEIODAD#v=onepage&q=%22in%201932%22%20%22prontosil%22&f=false}}</ref><ref name="Oxford Handbook of Infectious Diseases and Microbiology">{{cite book|last1=Torok|first1=Estee|last2=Moran|first2=Ed|last3=Cooke|first3=Fiona|title=Oxford Handbook of Infectious Diseases and Microbiology|url=https://books.google.com.ar/books?id=5W-WBQAAQBAJ&pg=PT56&redir_esc=y#v=onepage&q&f=false}}</ref> || {{w|Germany}}
@@ Line 48: / Line 48: @@
 | 1938 || Introduction || {{w|Sulfapyridine}} is introduced for clinical use for the treatment of pneumococcic pneumonia.<ref>{{cite web|title=Clinical Pharmacokinetics of Sulfonamides and Their Metabolites|url=https://www.karger.com/Article/Pdf/414206|website=karger.com|accessdate=1 April 2018}}</ref><ref>{{cite journal|last1=DETWEILER|first1=H. K.|last2=KINSEY|first2=H. I.|last3=HURST|first3=W.|title=TREATMENT OF PNEUMONIA WITH SULFAPYRIDINE|url=https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/545831?redirect=true}}</ref> Today it is used to help control {{w|dermatitis herpetiformis}} (Duhring's disease), a skin problem.<ref>{{cite web|title=Sulfapyridine (Oral Route)|url=https://www.mayoclinic.org/drugs-supplements/sulfapyridine-oral-route/description/drg-20066133|website=mayoclinic.org|accessdate=2 May 2018}}</ref> ||
 |-
-| 1939 || || Microbiologist {{w|René Dubos}} manages to isolate an antibacterial substance and names it {{w|tyrothricin}}.<ref name="René Dubos"/> ||
+| 1939 || Isolation || Microbiologist {{w|René Dubos}} manages to isolate an antibacterial substance and names it {{w|tyrothricin}}.<ref name="René Dubos"/> ||
 |-
 | 1939 || Introduction || {{w|Gramicidin A}} is discovered from the soil bacterium {{w|bacillus brevis}}, and becomes the first clinically useful topical antibiotic.<ref>{{cite book|last1=Bhattacharjee|first1=Mrinal K.|title=Chemistry of Antibiotics and Related Drugs|url=https://books.google.com.ar/books?id=vgXWDAAAQBAJ&pg=PA163&dq=%22in+1939%22+%22Gramicidin%22&hl=en&sa=X&ved=0ahUKEwio-9mTzKPaAhVHHpAKHcJhApYQ6AEIMjAC#v=onepage&q=%22in%201939%22%20%22Gramicidin%22&f=false}}</ref><ref>{{cite book|last1=Mouritsen|first1=Ole G.|title=Life - As a Matter of Fat: The Emerging Science of Lipidomics|url=https://books.google.com.ar/books?id=3J9enifNNTUC&pg=PA186&dq=%22in+1939%22+%22Gramicidin%22&hl=en&sa=X&ved=0ahUKEwio-9mTzKPaAhVHHpAKHcJhApYQ6AEILDAB#v=onepage&q=%22in%201939%22%20%22Gramicidin%22&f=false}}</ref><ref>{{cite book|title=Current Topics in Membranes and Transport, Volume 33|url=https://books.google.com.ar/books?id=Wktpa3-5HO8C&pg=PA15&dq=%22in+1939%22+%22Gramicidin%22&hl=en&sa=X&ved=0ahUKEwio-9mTzKPaAhVHHpAKHcJhApYQ6AEIKDAA#v=onepage&q=%22in%201939%22%20%22Gramicidin%22&f=false}}</ref> ||
@@ Line 66: / Line 66: @@
 | 1942 || Resistance || Penicillin resistant bacteria are first detected, about one year after the introduction of penicillin.<ref name="Antibiotic Resistance and the Biology of History"/> ||
 |-
-| 1942 || Introduction || {{w|Gramicidin S}}, the first {{w|peptide}} antibiotic, is isolated by Gauze and Brazhnikova.<ref>{{cite journal|last1=Berditsch|first1=Marina|last2=Afonin|first2=Sergii|last3=Ulrich|first3=Anne S.|title=The Ability of Aneurinibacillus migulanus (Bacillus brevis) To Produce the Antibiotic Gramicidin S Is Correlated with Phenotype Variation▿|url=http://aem.asm.org/content/73/20/6620.full?ck=nck}}</ref><ref>{{cite journal|last1=GAUSE|first1=G. F.|last2=BRAZHNIKOVA|first2=M. G.|title=Gramicidin S and its use in the Treatment of Infected Wounds|journal=Nature|doi=10.1038/154703a0|url=https://www.nature.com/articles/154703a0}}</ref><ref>{{cite book|last1=Korzybski|first1=Tadeusz|last2=Kowszyk-Gindifer|first2=Zuzanna|last3=Kurylowicz|first3=Wlodzimierz|title=Antibiotics: Origin, Nature and Properties|url=https://books.google.com.ar/books?id=JxElBQAAQBAJ&pg=PA48&dq=%22in+1942%22+%22gramicidin%22&hl=en&sa=X&ved=0ahUKEwiCj_nghZraAhVBkJAKHTcWDMoQ6AEIKDAA#v=onepage&q=%22in%201942%22%20%22gramicidin%22&f=false}}</ref> ||
+| 1942 || Isolation || {{w|Gramicidin S}}, the first {{w|peptide}} antibiotic, is isolated by Gauze and Brazhnikova.<ref>{{cite journal|last1=Berditsch|first1=Marina|last2=Afonin|first2=Sergii|last3=Ulrich|first3=Anne S.|title=The Ability of Aneurinibacillus migulanus (Bacillus brevis) To Produce the Antibiotic Gramicidin S Is Correlated with Phenotype Variation▿|url=http://aem.asm.org/content/73/20/6620.full?ck=nck}}</ref><ref>{{cite journal|last1=GAUSE|first1=G. F.|last2=BRAZHNIKOVA|first2=M. G.|title=Gramicidin S and its use in the Treatment of Infected Wounds|journal=Nature|doi=10.1038/154703a0|url=https://www.nature.com/articles/154703a0}}</ref><ref>{{cite book|last1=Korzybski|first1=Tadeusz|last2=Kowszyk-Gindifer|first2=Zuzanna|last3=Kurylowicz|first3=Wlodzimierz|title=Antibiotics: Origin, Nature and Properties|url=https://books.google.com.ar/books?id=JxElBQAAQBAJ&pg=PA48&dq=%22in+1942%22+%22gramicidin%22&hl=en&sa=X&ved=0ahUKEwiCj_nghZraAhVBkJAKHTcWDMoQ6AEIKDAA#v=onepage&q=%22in%201942%22%20%22gramicidin%22&f=false}}</ref> ||
 |-
 | 1943 || Introduction || American biochemists {{w|Selman Waksman}}, [[w:Albert Schatz (scientist)|Albert Schatz]], and Elizabeth Bugie discover antibiotic {{w|streptomycin}}, the first aminoglycoside. It is the first antibiotic effective against {{w|tuberculosis}}.<ref name="Ten important moments in the history of antibiotic discovery"/><ref>{{cite book|last1=Lorian|first1=Victor|title=Antibiotics in Laboratory Medicine|url=https://books.google.com.ar/books?id=HdA4dl8m_T4C&pg=PA197&dq=%22in+1943%22+%22streptomycin%22&hl=en&sa=X&ved=0ahUKEwjlxteRoYPaAhVRyVMKHZn_DQYQ6AEIKDAA#v=onepage&q=%22in%201943%22%20%22streptomycin%22&f=false}}</ref><ref>{{cite book|last1=Morabia|first1=Alfredo|title=Enigmas of Health and Disease: How Epidemiology Helps Unravel Scientific Mysteries|url=https://books.google.com.ar/books?id=H00ZBQAAQBAJ&pg=PA143&dq=%22in+1943%22+%22streptomycin%22&hl=en&sa=X&ved=0ahUKEwjlxteRoYPaAhVRyVMKHZn_DQYQ6AEIMzAC#v=onepage&q=%22in%201943%22%20%22streptomycin%22&f=false}}</ref><ref>{{cite book|last1=Cumo|first1=Christopher Martin|title=The Ongoing Columbian Exchange: Stories of Biological and Economic Transfer in World History: Stories of Biological and Economic Transfer in World History|url=https://books.google.com.ar/books?id=tzqhBgAAQBAJ&pg=PA319&dq=%22in+1943%22+%22streptomycin%22&hl=en&sa=X&ved=0ahUKEwjlxteRoYPaAhVRyVMKHZn_DQYQ6AEILTAB#v=onepage&q=%22in%201943%22%20%22streptomycin%22&f=false}}</ref><ref name="Oxford Handbook of Infectious Diseases and Microbiology"/> || {{w|United States}}
@@ Line 78: / Line 78: @@
 | 1945 || Introduction || The {{w|cephalosporins}} are discovered from a fungus, ''{{w|Cephalosporium acremonium}}'', in seawater samples near a sewage outfall in {{w|Sardinia}}.<ref name="Oxford Handbook of Infectious Diseases and Microbiology"/><ref>{{cite book|last1=Stephanie Watts|last2=Faingold|first2=Carl|last3=Dunaway|first3=George|last4=Crespo|first4=Lynn|title=Brody's Human Pharmacology - E-Book|url=https://books.google.com.ar/books?id=kfsrz_-OrMQC&pg=PA536&dq=%22in+1945%22+%22cephalosporins%22&hl=en&sa=X&ved=0ahUKEwjjl-6iooPaAhVFoFMKHRjiAWoQ6AEILDAB#v=onepage&q=%22in%201945%22%20%22cephalosporins%22&f=false}}</ref><ref>{{cite book|last1=Riviere|first1=Jim E.|last2=Papich|first2=Mark G.|title=Veterinary Pharmacology and Therapeutics|url=https://books.google.com.ar/books?id=ievLulSqwBAC&pg=PA865&dq=%22in+1945%22+%22cephalosporins%22&hl=en&sa=X&ved=0ahUKEwjjl-6iooPaAhVFoFMKHRjiAWoQ6AEINDAC#v=onepage&q=%22in%201945%22%20%22cephalosporins%22&f=false}}</ref><ref>{{cite book|last1=Bennett|first1=Peter N.|last2=Brown|first2=Morris J.|title=Clinical Pharmacology E-Book: With STUDENTCONSULT Access|url=https://books.google.com.ar/books?id=FaXRAQAAQBAJ&pg=PA193&dq=%22in+1945%22+%22cephalosporins%22&hl=en&sa=X&ved=0ahUKEwjjl-6iooPaAhVFoFMKHRjiAWoQ6AEIODAD#v=onepage&q=%22in%201945%22%20%22cephalosporins%22&f=false}}</ref> || {{w|Italy}}
 |-
-| 1947 || Introduction || {{w|Chloramphenicol}} is isolated from the soil organism ''{{w|Streptomyces venezuelae}}''. Merketed in 1949, its use would quickly become widespread due to its broad spectrum of antimicrobial activity.<ref>{{cite book|last1=Kacew|first1=Sam|title=Drug Toxicity and Metabolism in Pediatrics|url=https://books.google.com.ar/books?id=UrtHDwAAQBAJ&pg=PT262&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEILjAB#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Riviere|first1=Jim E.|last2=Papich|first2=Mark G.|title=Veterinary Pharmacology and Therapeutics|url=https://books.google.com.ar/books?id=ievLulSqwBAC&pg=PA946&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEINDAC#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Shapiro|first1=Stuart|title=Regulation of Secondary Metabolism in Actinomycetes|url=https://books.google.com.ar/books?id=pfZoaHwA1j0C&pg=PA167&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEIODAD#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Aschenbrenner|first1=Diane S.|last2=Venable|first2=Samantha J.|title=Drug Therapy in Nursing|url=https://books.google.com.ar/books?id=5zd_W_PUwvYC&pg=PA800&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEIKDAA#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref> ||
+| 1947 || Isolation || {{w|Chloramphenicol}} is isolated from the soil organism ''{{w|Streptomyces venezuelae}}''. Merketed in 1949, its use would quickly become widespread due to its broad spectrum of antimicrobial activity.<ref>{{cite book|last1=Kacew|first1=Sam|title=Drug Toxicity and Metabolism in Pediatrics|url=https://books.google.com.ar/books?id=UrtHDwAAQBAJ&pg=PT262&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEILjAB#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Riviere|first1=Jim E.|last2=Papich|first2=Mark G.|title=Veterinary Pharmacology and Therapeutics|url=https://books.google.com.ar/books?id=ievLulSqwBAC&pg=PA946&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEINDAC#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Shapiro|first1=Stuart|title=Regulation of Secondary Metabolism in Actinomycetes|url=https://books.google.com.ar/books?id=pfZoaHwA1j0C&pg=PA167&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEIODAD#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref><ref>{{cite book|last1=Aschenbrenner|first1=Diane S.|last2=Venable|first2=Samantha J.|title=Drug Therapy in Nursing|url=https://books.google.com.ar/books?id=5zd_W_PUwvYC&pg=PA800&dq=%22in+1947%22+%22chloramphenicol%22&hl=en&sa=X&ved=0ahUKEwiepeLgo4PaAhUFsFMKHc4IAAUQ6AEIKDAA#v=onepage&q=%22in%201947%22%20%22chloramphenicol%22&f=false}}</ref> ||
 |-
-| 1947 || Scientific development || American plant physiologist {{w|Benjamin Minge Duggar}} isolates {{w|chlortetracycline}} from a {{w|Missouri River}} mud sample. It is the first {{w|tetracycline}} introduced.<ref>{{cite book|last1=Dougherty|first1=Thomas J.|last2=Pucci|first2=Michael J.|title=Antibiotic Discovery and Development|url=https://books.google.com.ar/books?id=av5SHPiHVcsC&pg=PA152&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEIKDAA#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|last1=Kokate|first1=Chandrakant|last2=Jalalpure|first2=SS|last3=Pramod|first3=H.J|title=Textbook of Pharmaceutical Biotechnology - E-Book|url=https://books.google.com.ar/books?id=p70UCwAAQBAJ&pg=PA170&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEILTAB#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|title=Advances in Pharmacology and Chemotherapy|url=https://books.google.com.ar/books?id=MyNwTA-iWvgC&pg=PA163&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEINTAC#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|last1=McKenna|first1=John|title=Natural Alternatives to Antibiotics – Revised and Updated: How to treat infections without antibiotics|url=https://books.google.com.ar/books?id=T0t_BAAAQBAJ&pg=PT23&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEIOjAD#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref> || {{w|United States}}
+| 1947 || Isolation || American plant physiologist {{w|Benjamin Minge Duggar}} isolates {{w|chlortetracycline}} from a {{w|Missouri River}} mud sample. It is the first {{w|tetracycline}} introduced.<ref>{{cite book|last1=Dougherty|first1=Thomas J.|last2=Pucci|first2=Michael J.|title=Antibiotic Discovery and Development|url=https://books.google.com.ar/books?id=av5SHPiHVcsC&pg=PA152&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEIKDAA#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|last1=Kokate|first1=Chandrakant|last2=Jalalpure|first2=SS|last3=Pramod|first3=H.J|title=Textbook of Pharmaceutical Biotechnology - E-Book|url=https://books.google.com.ar/books?id=p70UCwAAQBAJ&pg=PA170&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEILTAB#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|title=Advances in Pharmacology and Chemotherapy|url=https://books.google.com.ar/books?id=MyNwTA-iWvgC&pg=PA163&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEINTAC#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref><ref>{{cite book|last1=McKenna|first1=John|title=Natural Alternatives to Antibiotics – Revised and Updated: How to treat infections without antibiotics|url=https://books.google.com.ar/books?id=T0t_BAAAQBAJ&pg=PT23&dq=%22in+1947%22%22chlortetracycline%22&hl=en&sa=X&ved=0ahUKEwisr8DXqIPaAhVOrFMKHa2-DiIQ6AEIOjAD#v=onepage&q=%22in%201947%22%22chlortetracycline%22&f=false}}</ref> || {{w|United States}}
 |-
-| 1947 || Introduction || Antibiotic {{w|polymyxin}} family of antibiotics is discovered, with {{w|polymyxin B}} being the first isolated from bavterium {{w|paenibacillus polymyxa}}.<ref name="Ten important moments in the history of antibiotic discovery"/><ref>{{cite book|title=Antimicrobial Cationic Peptides—Advances in Research and Application: 2013 Edition: ScholarlyBrief|url=https://books.google.com.ar/books?id=NKsalcHkxmAC&pg=PA74&dq=%22in+1947%22+%22polymyxin%22&hl=en&sa=X&ved=0ahUKEwixxNmOoZfaAhVLipAKHR6QCwsQ6AEIKDAA#v=onepage&q=%22in%201947%22%20%22polymyxin%22&f=false}}</ref><ref>{{cite book|title=Annual Reports in Medicinal Chemistry, Volume 46|publisher=Academic Press, Oct 12, 2011 - Science|url=https://books.google.com.ar/books?id=_PWJ3dJWG7oC&pg=PA254&dq=%22in+1947%22+%22polymyxin%22&hl=en&sa=X&ved=0ahUKEwixxNmOoZfaAhVLipAKHR6QCwsQ6AEILTAB#v=onepage&q=%22in%201947%22%20%22polymyxin%22&f=false}}</ref> ||
+| 1947 || Isolation || Antibiotic {{w|polymyxin}} family of antibiotics is discovered, with {{w|polymyxin B}} being the first isolated from bavterium {{w|paenibacillus polymyxa}}.<ref name="Ten important moments in the history of antibiotic discovery"/><ref>{{cite book|title=Antimicrobial Cationic Peptides—Advances in Research and Application: 2013 Edition: ScholarlyBrief|url=https://books.google.com.ar/books?id=NKsalcHkxmAC&pg=PA74&dq=%22in+1947%22+%22polymyxin%22&hl=en&sa=X&ved=0ahUKEwixxNmOoZfaAhVLipAKHR6QCwsQ6AEIKDAA#v=onepage&q=%22in%201947%22%20%22polymyxin%22&f=false}}</ref><ref>{{cite book|title=Annual Reports in Medicinal Chemistry, Volume 46|publisher=Academic Press, Oct 12, 2011 - Science|url=https://books.google.com.ar/books?id=_PWJ3dJWG7oC&pg=PA254&dq=%22in+1947%22+%22polymyxin%22&hl=en&sa=X&ved=0ahUKEwixxNmOoZfaAhVLipAKHR6QCwsQ6AEILTAB#v=onepage&q=%22in%201947%22%20%22polymyxin%22&f=false}}</ref> ||
 |-
 | 1947 || Introduction || {{w|Nitrofuran}} is introduced.<ref name="Antibiotics armageddon?"/> ||
 |-
-| 1949 || || Jewish-American biochemist {{w|Selman Waksman}} and Hubert A. Lechevalier first isolate {{w|neomycin}}, as {{w|aminoglycoside}} antibiotic found in many topical medications such as creams, ointments, and eyedrops.<ref>{{cite book|last1=Schindel|first1=Leo|title=Unexpected Reactions to Modern Therapeutics: Antibiotics|url=https://books.google.com.ar/books?id=ff_fBAAAQBAJ&pg=PA102&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEIMDAB#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref><ref>{{cite book|last1=Grayson|first1=M Lindsay|last2=Crowe|first2=Suzanne M|last3=McCarthy|first3=James S|last4=Mills|first4=John|last5=Mouton|first5=Johan W|last6=Norrby|first6=S Ragnar|last7=Paterson|first7=David L|last8=Pfaller|first8=Michael A|title=Kucers' The Use of Antibiotics Sixth Edition: A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs|url=https://books.google.com.ar/books?id=XR3cBQAAQBAJ&pg=PA742&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEIKDAA#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref><ref>{{cite book|title=Advances in Carbohydrate Chemistry, Volume 18|url=https://books.google.com.ar/books?id=Nwu3tgVqx3IC&pg=PA266&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEINjAC#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref> || {{w|United States}}
+| 1949 || Isolation || Jewish-American biochemist {{w|Selman Waksman}} and Hubert A. Lechevalier first isolates {{w|neomycin}}, as {{w|aminoglycoside}} antibiotic found in many topical medications such as creams, ointments, and eyedrops.<ref>{{cite book|last1=Schindel|first1=Leo|title=Unexpected Reactions to Modern Therapeutics: Antibiotics|url=https://books.google.com.ar/books?id=ff_fBAAAQBAJ&pg=PA102&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEIMDAB#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref><ref>{{cite book|last1=Grayson|first1=M Lindsay|last2=Crowe|first2=Suzanne M|last3=McCarthy|first3=James S|last4=Mills|first4=John|last5=Mouton|first5=Johan W|last6=Norrby|first6=S Ragnar|last7=Paterson|first7=David L|last8=Pfaller|first8=Michael A|title=Kucers' The Use of Antibiotics Sixth Edition: A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs|url=https://books.google.com.ar/books?id=XR3cBQAAQBAJ&pg=PA742&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEIKDAA#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref><ref>{{cite book|title=Advances in Carbohydrate Chemistry, Volume 18|url=https://books.google.com.ar/books?id=Nwu3tgVqx3IC&pg=PA266&dq=%22neomycin%22+%22in+1949%22&hl=en&sa=X&ved=0ahUKEwjEo_rIsoPaAhXN51MKHXGiDTMQ6AEINjAC#v=onepage&q=%22neomycin%22%20%22in%201949%22&f=false}}</ref> || {{w|United States}}
 |-
 | 1949 || Scientific development || British chemist {{w|Dorothy Hodgkin}} reveals the complete structure of molecular {{w|penicillin}}, using the X-ray crystallography.<ref name="Origins and Evolution of Antibiotic Resistance"/> || {{w|United Kingdom}}
@@ Line 112: / Line 112: @@
 | 1955 || Introduction || {{w|Macrolide}} antibiotic {{w|spiramycin}} is first introduced into the French market.<ref>{{cite book|last1=Lancini|first1=Giancarlo|last2=Parenti|first2=Francesco|title=Antibiotics: An Integrated View|url=https://books.google.com.ar/books?id=5VjSBwAAQBAJ&pg=PA141&lpg=PA141&dq=%22in+1955%22+%22spiramycin%22&source=bl&ots=aXcqRwkVQR&sig=pw34DhdXBLqw26AYVIcKYKXu0Qg&hl=en&sa=X&ved=0ahUKEwiyks39ypraAhUGGJAKHaJ-DX8Q6AEIMDAB#v=onepage&q=%22in%201955%22%20%22spiramycin%22&f=false}}</ref> || {{w|France}}
 |-
-| 1956 || Introduction || Research team at the {{w|Lilly Biological Laboratories}} in {{w|Indiana}} first isolates {{w|vancomycin}} from bacterium {{w|streplomyces orienlalis}}. {{w|Vancomycin}} is used as a treatment for complicated {{w|skin infections}}, bloodstream infections, {{w|endocarditis}}, bone and joint infections, and meningitis caused by methicillin-resistant {{w|staphylococcus aureus}}.<ref name="Oxford Handbook of Infectious Diseases and Microbiology"/><ref>{{cite book|title=Staphylococci in Human Disease|edition=Kent B. Crossley, Kimberly K. Jefferson, Gordon L. Archer, Vance G. Fowler|url=https://books.google.com.ar/books?id=4HdJ1t6NOIcC&pg=PA193&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjC_KOGkd7ZAhXBjZAKHUNpDZgQ6AEILzAB#v=onepage&q=%22in%201956%22%20%22vancomycin%22&f=false}}</ref><ref>{{cite book|title=Antibiotics Annual|url=https://books.google.com.ar/books?id=6-o5AAAAMAAJ&q=%22in+1956%22+%22vancomycin%22&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjm1vv6uIPaAhVHyVMKHSaVBos4ChDoAQgxMAI}}</ref><ref>{{cite book|last1=Hejzlar|first1=Miroslav|title=Advances in Antimicrobial and Antineoplastic Chemotherapy: Progress in Research and Clinical Application: pt. 1-2. Antimicrobial chemotherapy|url=https://books.google.com.ar/books?id=qN9sAAAAMAAJ&q=%22in+1956%22+%22vancomycin%22&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjm1vv6uIPaAhVHyVMKHSaVBos4ChDoAQgnMAA}}</ref> || {{w|United States}}
+| 1956 || Isolation || Research team at the {{w|Lilly Biological Laboratories}} in {{w|Indiana}} first isolates {{w|vancomycin}} from bacterium {{w|streplomyces orienlalis}}. {{w|Vancomycin}} is used as a treatment for complicated {{w|skin infections}}, bloodstream infections, {{w|endocarditis}}, bone and joint infections, and meningitis caused by methicillin-resistant {{w|staphylococcus aureus}}.<ref name="Oxford Handbook of Infectious Diseases and Microbiology"/><ref>{{cite book|title=Staphylococci in Human Disease|edition=Kent B. Crossley, Kimberly K. Jefferson, Gordon L. Archer, Vance G. Fowler|url=https://books.google.com.ar/books?id=4HdJ1t6NOIcC&pg=PA193&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjC_KOGkd7ZAhXBjZAKHUNpDZgQ6AEILzAB#v=onepage&q=%22in%201956%22%20%22vancomycin%22&f=false}}</ref><ref>{{cite book|title=Antibiotics Annual|url=https://books.google.com.ar/books?id=6-o5AAAAMAAJ&q=%22in+1956%22+%22vancomycin%22&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjm1vv6uIPaAhVHyVMKHSaVBos4ChDoAQgxMAI}}</ref><ref>{{cite book|last1=Hejzlar|first1=Miroslav|title=Advances in Antimicrobial and Antineoplastic Chemotherapy: Progress in Research and Clinical Application: pt. 1-2. Antimicrobial chemotherapy|url=https://books.google.com.ar/books?id=qN9sAAAAMAAJ&q=%22in+1956%22+%22vancomycin%22&dq=%22in+1956%22+%22vancomycin%22&hl=en&sa=X&ved=0ahUKEwjm1vv6uIPaAhVHyVMKHSaVBos4ChDoAQgnMAA}}</ref> || {{w|United States}}
 |-
 | 1956 || Introduction || {{w|Glycopeptide}}s are introduced.<ref name="Antibiotics armageddon?"/> ||
@@ Line 138: / Line 138: @@
 | 1962 || Introduction || {{w|Quinolone}}s are discovered accidentally, as a byproduct of some research on the antimalarial drug {{w|chloroquine}}.<ref name="Ten important moments in the history of antibiotic discovery"/><ref name="Antibiotics armageddon?"/> ||
 |-
-| 1963 || Introduction || Weinstein and his colleagues from the [[w:Schering-Plough|Schering Corporation]] describe the first isolation of the {{w|gentamicin}} complex.<ref name="Oxford Handbook of Infectious Diseases and Microbiology"/><ref>{{cite book|title=Advances in Applied Microbiology, Volume 18|url=https://books.google.com.ar/books?id=4e3RAZyEf3IC&pg=PA203&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEIKDAA#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref><ref>{{cite book|last1=Eardley|first1=Ian|last2=Whelan|first2=Peter|last3=Kirby|first3=Roger|last4=Schaeffer|first4=Anthony|title=Drug Treatment in Urology|url=https://books.google.com.ar/books?id=S903KFrQAC8C&pg=PA97&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEILTAB#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref><ref>{{cite book|title=Antimicrobials: Synthetic and Natural Compounds|edition=Dharumadurai Dhanasekaran, Nooruddin Thajuddin, A. Panneerselvam|url=https://books.google.com.ar/books?id=HZLwCgAAQBAJ&pg=PA102&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEIMjAC#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref> || {{w|United States}}
+| 1963 || Isolation || Weinstein and his colleagues from the [[w:Schering-Plough|Schering Corporation]] describe the first isolation of the {{w|gentamicin}} complex.<ref name="Oxford Handbook of Infectious Diseases and Microbiology"/><ref>{{cite book|title=Advances in Applied Microbiology, Volume 18|url=https://books.google.com.ar/books?id=4e3RAZyEf3IC&pg=PA203&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEIKDAA#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref><ref>{{cite book|last1=Eardley|first1=Ian|last2=Whelan|first2=Peter|last3=Kirby|first3=Roger|last4=Schaeffer|first4=Anthony|title=Drug Treatment in Urology|url=https://books.google.com.ar/books?id=S903KFrQAC8C&pg=PA97&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEILTAB#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref><ref>{{cite book|title=Antimicrobials: Synthetic and Natural Compounds|edition=Dharumadurai Dhanasekaran, Nooruddin Thajuddin, A. Panneerselvam|url=https://books.google.com.ar/books?id=HZLwCgAAQBAJ&pg=PA102&dq=%22in+1963%22+%22gentamicin%22&hl=en&sa=X&ved=0ahUKEwjj1uS7mY7aAhXDkJAKHY7kCS8Q6AEIMjAC#v=onepage&q=%22in%201963%22%20%22gentamicin%22&f=false}}</ref> || {{w|United States}}
 |-
 | 1963 || Introduction || {{w|Gentamicin}} is discovered. It is used to treat several types of bacterial infections.<ref name="The Golden Age of Antibacterials"/> ||
@@ Line 164: / Line 164: @@
 | 1971 || Introduction || {{w|Aminoglycoside}} {{w|antibiotic}} {{w|Tobramycin}} is discovered. It is used to treat various types of bacterial infections, particularly {{w|Gram-negative}} infections.<ref name="The Golden Age of Antibacterials"/> ||
 |-
-| 1972 || Introduction || Extracellular broad spectrum {{w|beta-lactam antibiotic}} {{w|cephamycin}} C is first isolated.<ref>{{cite book|last1=Diana|first1=Patrizia|last2=Cirrincione|first2=Girolamo|title=Biosynthesis of Heterocycles: From Isolation to Gene Cluster|url=https://books.google.com.ar/books?id=dQ91BgAAQBAJ&pg=PA320&lpg=PA320&dq=%22in+1972%22+%22Cephamycin%22&source=bl&ots=jQaDvsvSHp&sig=rte-hL9RKlNXTRPQXIsDggTof_E&hl=en&sa=X&ved=0ahUKEwiF8_fPqOfaAhVITZAKHQm_CroQ6AEIOTAC#v=onepage&q=%22in%201972%22%20%22Cephamycin%22&f=false}}</ref><ref name="The Golden Age of Antibacterials"/> ||
+| 1972 || Isolation || Extracellular broad spectrum {{w|beta-lactam antibiotic}} {{w|cephamycin}} C is first isolated.<ref>{{cite book|last1=Diana|first1=Patrizia|last2=Cirrincione|first2=Girolamo|title=Biosynthesis of Heterocycles: From Isolation to Gene Cluster|url=https://books.google.com.ar/books?id=dQ91BgAAQBAJ&pg=PA320&lpg=PA320&dq=%22in+1972%22+%22Cephamycin%22&source=bl&ots=jQaDvsvSHp&sig=rte-hL9RKlNXTRPQXIsDggTof_E&hl=en&sa=X&ved=0ahUKEwiF8_fPqOfaAhVITZAKHQm_CroQ6AEIOTAC#v=onepage&q=%22in%201972%22%20%22Cephamycin%22&f=false}}</ref><ref name="The Golden Age of Antibacterials"/> ||
 |-
 | 1972 || Introduction || Antibiotic {{w|minocycline}} is discovered.<ref name="Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice"/><ref name="Hugo and Russell's Pharmaceutical Microbiology"/><ref name="Neuroinflammation in Stroke"/> ||

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