streptomycin

• Infective endocarditis: An infection of the endocardium caused by enterococcus; used when the organism is not sensitive to gentamicin{{medcn|date=October 2020}}
• Tuberculosis: Used in combination with other antibiotics. For active tuberculosis it is often given together with isoniazid, rifampicin, and pyrazinamide. It is not the first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive. It may be useful in cases where resistance to other drugs is identified.{{medcn|date=October 2020}}
• Plague (Yersinia pestis): Has historically been used as the first-line treatment. However streptomycin is approved for this purpose only by the US Food and Drug Administration.{{medcn|date=October 2020}}
• In veterinary medicine, streptomycin is the first-line antibiotic for use against gram negative bacteria in large animals (horses, cattle, sheep, etc.). It is commonly combined with procaine penicillin for intramuscular injection.{{medcn|date=October 2020}}
• Tularemia infections have been treated mostly with streptomycin.{{cite web|title=Clinicians Tularemia |url=https://www.cdc.gov/tularemia/clinicians/index.html|website=www.cdc.gov|access-date=November 8, 2017|language=en-us|date=September 2016}}

Streptomycin is traditionally given intramuscularly, and in many nations is only licensed to be administered intramuscularly, though in some regions the drug may also be administered intravenously.{{cite journal | vauthors = Zhu M, Burman WJ, Jaresko GS, Berning SE, Jelliffe RW, Peloquin CA | title = Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis | journal = Pharmacotherapy | volume = 21 | issue = 9 | pages = 1037–1045 | date = September 2001 | pmid = 11560193 | doi = 10.1592/phco.21.13.1037.34625 | url = http://www.medscape.com/viewarticle/409778 | access-date = May 25, 2010 | url-status = live | s2cid = 24111273 | archive-url = https://web.archive.org/web/20111005005316/http://www.medscape.com/viewarticle/409778 | archive-date = October 5, 2011 | url-access = subscription }}

Streptomycin also is used as a pesticide, to combat the growth of bacteria beyond human applications. Streptomycin controls bacterial diseases of certain fruit, vegetables, seed, and ornamental crops. A major use is in the control of fireblight on apple and pear trees. As in medical applications, extensive use can be associated with the development of resistant strains. Streptomycin could potentially be used to control cyanobacterial blooms in ornamental ponds and aquaria.{{cite journal | vauthors = Qian H, Li J, Pan X, Sun Z, Ye C, Jin G, Fu Z | title = Effects of streptomycin on growth of algae Chlorella vulgaris and Microcystis aeruginosa | journal = Environmental Toxicology | volume = 27 | issue = 4 | pages = 229–237 | date = March 2012 | pmid = 20725941 | doi = 10.1002/tox.20636 | s2cid = 2380252 | bibcode = 2012EnTox..27..229Q }} While some antibacterial antibiotics are inhibitory to certain eukaryotes, this seems not to be the case for streptomycin, especially in the case of anti-fungal activity.{{cite journal | vauthors = Reilly HC, Schatz A, Waksman SA | title = Antifungal Properties of Antibiotic Substances | journal = Journal of Bacteriology | volume = 49 | issue = 6 | pages = 585–594 | date = June 1945 | pmid = 16560957 | pmc = 374091 | doi = 10.1128/jb.49.6.585-594.1945 }}

Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.{{cite journal | vauthors = Phelan K, May KM | title = Basic techniques in mammalian cell tissue culture | journal = Current Protocols in Cell Biology | volume = 66 | issue = 1 | pages = 1.1.1–1.1.22 | date = March 2015 | pmid = 25727327 | doi = 10.1002/0471143030.cb0101s66 | s2cid = 29881502 }}

When purifying protein from a biological extract, streptomycin sulfate is sometimes added as a means of removing nucleic acids and ribonuclear proteins. Since it binds to ribosomes and precipitates out of solution, it serves as a method for removing rRNA, mRNA, and even DNA if the extract is from a prokaryote.{{cite book | vauthors = Scopes RK | title=Protein purification : principles and practice | publisher=Springer-Verlag | publication-place=New York | date=1994 | isbn=978-1-4757-2333-5 | oclc=620957612 | page=37}}

The most concerning side effects, as with other aminoglycosides, are kidney toxicity and ear toxicity.{{cite journal | vauthors = Prayle A, Watson A, Fortnum H, Smyth A | title = Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis | journal = Thorax | volume = 65 | issue = 7 | pages = 654–658 | date = July 2010 | pmid = 20627927 | pmc = 2921289 | doi = 10.1136/thx.2009.131532 }} Transient or permanent deafness may result. The vestibular portion of cranial nerve VIII (the vestibulocochlear nerve) can be affected, resulting in tinnitus, vertigo, ataxia, kidney toxicity, and can potentially interfere with diagnosis of kidney malfunction.{{cite journal | vauthors = Syal K, Srinivasan A, Banerjee D | title = Streptomycin interference in Jaffe reaction - possible false positive creatinine estimation in excessive dose exposure | journal = Clinical Biochemistry | volume = 46 | issue = 1–2 | pages = 177–179 | date = January 2013 | pmid = 23123914 | doi = 10.1016/j.clinbiochem.2012.10.031 }}

Common side effects include vertigo, vomiting, numbness of the face, fever, and rash. Fever and rashes may result from persistent use.{{citation needed|date=October 2018}}

Use is not recommended during pregnancy. Congenital deafness has been reported in children whose mothers received streptomycin during pregnancy. Use appears to be okay while breastfeeding.

It is not recommended in people with myasthenia gravis.

Streptomycin functions as a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S ribosomal subunit irreversibly, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit.{{cite journal | vauthors = Sharma D, Cukras AR, Rogers EJ, Southworth DR, Green R | title = Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome | journal = Journal of Molecular Biology | volume = 374 | issue = 4 | pages = 1065–1076 | date = December 2007 | pmid = 17967466 | pmc = 2200631 | doi = 10.1016/j.jmb.2007.10.003 }}

This causes codon misreading, inhibition of protein synthesis, and ultimately death of the cell through mechanisms that are not well understood. Speculation indicates that the binding of the molecule to the 30S subunit interferes with 30S subunit association with the mRNA strand. This results in an unstable ribosomal-mRNA complex, leading to premature stopping of protein synthesis, leading to cell death.{{cite book| vauthors = Raymon LP |title=COMLEX Level 1 Pharmacology Lecture Notes|year=2011|publisher=Kaplan, Inc.|location=Miami, FL|id=CM4024K|pages=181}} As human and bacteria both have ribosomes, streptomycin has significant side effects in humans. At low concentrations, however, streptomycin inhibits only bacterial growth.

{{cite book| vauthors = Voet D, Voet JG | title = Biochemistry|url=https://archive.org/details/biochemistry00voet_1 |url-access=registration | edition = 3rd| publisher = John Wiley & Sons| page = [https://archive.org/details/biochemistry00voet_1/page/1341 1341]| year = 2004| isbn = 978-0-471-19350-0 }}

Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria,{{cite book|title=A manual for primary human cell culture|year=2004|publisher=World Scientific| vauthors = Schantz JT, Ng KW |page=89}} and is therefore a useful broad-spectrum antibiotic.

Streptomycin was first isolated on October 19, 1943, by Albert Schatz, a PhD student in the laboratory of Selman Abraham Waksman at Rutgers University in a research project funded by Merck and Co.

{{cite journal | vauthors = Comroe JH | title = Pay dirt: the story of streptomycin. Part I. From Waksman to Waksman | journal = The American Review of Respiratory Disease | volume = 117 | issue = 4 | pages = 773–781 | date = April 1978 | pmid = 417651 | doi = 10.1164/arrd.1978.117.4.773 | doi-broken-date = November 1, 2024 }}

{{cite journal | vauthors = Kingston W | title = Streptomycin, Schatz v. Waksman, and the balance of credit for discovery | journal = Journal of the History of Medicine and Allied Sciences | volume = 59 | issue = 3 | pages = 441–462 | date = July 2004 | pmid = 15270337 | doi = 10.1093/jhmas/jrh091 | s2cid = 27465970 }} Waksman and his laboratory staff discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein, neomycin, fradicin, candicidin, and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first antibiotic cure for tuberculosis (TB). In 1952 Waksman was the recipient of the Nobel Prize in Physiology or Medicine in recognition "for his discovery of streptomycin, the first antibiotic active against tuberculosis".{{Cite web|url=https://www.nobelprize.org/prizes/lists/all-nobel-laureates-in-physiology-or-medicine|archive-url=https://web.archive.org/web/20170609092934/http://www.nobelprize.org/nobel_prizes/medicine/laureates/index.html|url-status=dead|title=All Nobel Prizes in Physiology or Medicine|archive-date=June 9, 2017|website=NobelPrize.org}} Waksman was later accused of playing down the role of Schatz who did the work under his supervision, claiming that Elizabeth Bugie had a more important role in its development.{{Cite web|title=Obiturary: Elizabeth Gregory / Did McCandless woman get fair shake for role in discovery of streptomycin?|url=http://old.post-gazette.com/obituaries/20010414gregory2.asp|access-date=November 7, 2021|website=old.post-gazette.com|archive-date=November 29, 2021|archive-url=https://web.archive.org/web/20211129213617/http://old.post-gazette.com/obituaries/20010414gregory2.asp|url-status=dead}}{{cite book|url=https://books.google.com/books?id=dRWLQgAACAAJ|title=Miracle Cure: The Story of Penicillin and the Golden Age of Antibiotics|date=1990|publisher=Blackwell|isbn=9780631164920| vauthors = Wainwright M |access-date=December 29, 2014|url-status=live|archive-url=https://web.archive.org/web/20170910172645/https://books.google.com/books?id=dRWLQgAACAAJ|archive-date=September 10, 2017}}{{cite journal | vauthors = Wainwright M | title = Streptomycin: discovery and resultant controversy | journal = History and Philosophy of the Life Sciences | volume = 13 | issue = 1 | pages = 97–124 | date = 1991 | pmid = 1882032 }}{{cite journal | vauthors = Kingston W | title = Streptomycin, Schatz v. Waksman, and the balance of credit for discovery | journal = Journal of the History of Medicine and Allied Sciences | volume = 59 | issue = 3 | pages = 441–462 | date = July 2004 | pmid = 15270337 | doi = 10.1093/jhmas/jrh091 | s2cid = 27465970 }}{{Cite book|title=Experiment Eleven: Dark Secrets Behind the Discovery of a Wonder Drug| vauthors = Pringle P |publisher=Walker & Company|year=2012|isbn=978-1620401989|location=New York}} Schatz sued both Dr. Waksman and the Rutgers Research and Endowment Foundation, wanting to be given credit as co-discover and to receive the royalties for the streptomycin.{{Cite web|title=Elizabeth Bugie – the invisible woman in the discovery of streptomycin|url=http://www.scientistafoundation.com/35/post/2018/08/elizabeth-bugie-the-invisible-woman-in-the-discovery-of-streptomycin.html|access-date=November 30, 2021|website=The Scientista Foundation|language=en}} By the end of the settlement, Waksman would receive a 10% royalty, while Schatz got 3% and compensation for his missed royalties.{{Cite web|title=The Forgotten Women of the Antibiotics Race|url=https://www.ladyscience.com/features/forgotten-women-researchers-in-the-race-for-antibiotics-2021|access-date=December 21, 2021|website=Lady Science|date=July 22, 2021 |language=en-US}} The rest of the lab shared the remaining 7% of the royalties, in which Bugie received 0.2%.{{cn|date=August 2022}}

Bugie was pursuing a master's degree in Waksman's lab at Rutgers University at this time. Prior to this, she received her bachelor's degree in microbiology at New Jersey College for Women. Although Bugie was considered to be the second author on the Proceedings of the Society for Experimental Biology paper, she was not listed on the patent submission. Bugie's contributions to Waksman's lab were great. In addition to her work on streptomycin, she also helped develop other antimicrobial substances,{{Cite book|url=https://onlinelibrary.wiley.com/doi/book/10.1128/9781555819545| chapter-url=https://onlinelibrary.wiley.com/doi/10.1128/9781555819545.ch34|isbn=9781555819545|doi=10.1128/9781555819545|title=Women in Microbiology|chapter=Women Microbiologists at Rutgers in the Early Golden Age of Antibiotics| year=2018| publisher=American Society of Microbiology| veditors = Whitaker RJ, Barton HB }} had two peer-reviewed publications,{{cite journal | vauthors = Waksman SA, Bugie E | title = Strain Specificity and Production of Antibiotic Substances: II. Aspergillus Flavus-Oryzae Group | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 29 | issue = 9 | pages = 282–288 | date = September 1943 | pmid = 16578091 | pmc = 1078613 | doi = 10.1073/pnas.29.9.282 | doi-access = free | bibcode = 1943PNAS...29..282W }}{{cite journal | vauthors = Waksman SA, Bugie E | title = Chaetomin, a New Antibiotic Substance Produced by Chaetomium cochliodes: I. Formation and Properties | journal = Journal of Bacteriology | volume = 48 | issue = 5 | pages = 527–530 | date = November 1944 | pmid = 16560863 | pmc = 374002 | doi = 10.1128/jb.48.5.527-530.1944 }} and researched the use of antimicrobials against plant pathogens,{{Cite journal| vauthors = Waksman SA, Bugie E |date=October 1, 1943|title=Action of Antibiotic Substances Upon Ceratostotnella ulmi |journal=Experimental Biology and Medicine|volume=54|issue=1|pages=79–82|doi=10.3181/00379727-54-14310|s2cid=87534513|issn=1535-3702}} among several other important contributions to the scientific field, particularly in regard to microbiology.

File:Streptomycin assay.jpg

The Rutgers team reported streptomycin in the medical literature in January 1944.{{cite journal | vauthors = Schatz A, Bugle E, Waksman SA |year=1944 |title=Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria |journal=Experimental Biology and Medicine |volume=55 |pages=66–69 |doi=10.3181/00379727-55-14461 |s2cid=33680180 }} Within months they began working with William Feldman and H. Corwin Hinshaw of the Mayo Clinic with hopes of starting a human clinical trial of streptomycin in tuberculosis.{{cite book | vauthors = Ryan F | year = 1993 | title = The forgotten plague: how the battle against tuberculosis was won—and lost | publisher = Little, Brown | location = Boston | isbn = 978-0316763806 | url-access = registration | url = https://archive.org/details/forgottenplagueh00ryan }}{{rp|209–241}} The difficulty at first was even producing enough streptomycin to do a trial, because the research laboratory methods of creating small batches had not yet been translated to commercial large-batch production. They managed to do an animal study in a few guinea pigs with just 10 grams of the scarce drug, demonstrating survival.{{rp|209–241}} This was just enough evidence to get Merck & Co. to divert some resources from the young penicillin production program to start work toward streptomycin production.{{rp|209–241}}

At the end of World War II, the United States Army experimented with streptomycin to treat life-threatening infections at a military hospital in Battle Creek, Michigan. The first person who was treated with streptomycin did not survive; the second person survived but became blind as a side effect of the treatment. In March 1946, the third person—Robert J. Dole, later Majority Leader of the United States Senate and presidential nominee—experienced a rapid and robust recovery.{{cite book | vauthors = Cramer RB |title=What it takes : the way to the White House |date=1992 |publisher=Random House |location=New York |isbn=978-0-394-56260-5 |edition=1st | pages = 110–111 }}

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946 through 1948 by the MRC Tuberculosis Research Unit under the chairmanship of Geoffrey Marshall (1887–1982). The trial was neither double-blind nor placebo-controlled. It is widely accepted to have been the first randomized curative trial.{{cite journal | vauthors = Metcalfe NH | title = Sir Geoffrey Marshall (1887-1982): respiratory physician, catalyst for anaesthesia development, doctor to both Prime Minister and King, and World War I Barge Commander | journal = Journal of Medical Biography | volume = 19 | issue = 1 | pages = 10–14 | date = February 2011 | pmid = 21350072 | doi = 10.1258/jmb.2010.010019 | s2cid = 39878743 }}

Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug.{{cite journal | vauthors = D'Arcy Hart P | title = A change in scientific approach: from alternation to randomised allocation in clinical trials in the 1940s | journal = BMJ | volume = 319 | issue = 7209 | pages = 572–573 | date = August 1999 | pmid = 10463905 | pmc = 1116443 | doi = 10.1136/bmj.319.7209.572 }}

Because streptomycin was isolated from a microbe discovered on New Jersey soil, and because of its activity against tuberculosis and Gram negative organisms, and in recognition of both the microbe and the antibiotic in the history of New Jersey, S. griseus was nominated as the Official New Jersey state microbe. The draft legislation was submitted by Senator Sam Thompson (R-12) in May 2017 as bill S3190 and Assemblywoman Annette Quijano (D-20) in June 2017 as bill A31900. The bill was passed on 2018-01-08 The bill designates Streptomyces griseus as New Jersey State Microbe (New Jersey Senate Bill 3190 (2017). Governor Phil Murphy signed the bill making it official in 2019.{{Cite web |title=New Jersey gets official state microbe: Streptomyces griseus |url=https://whyy.org/articles/new-jersey-gets-official-state-microbe-streptomyces-griseus/ |date=May 11, 2019 |website=WHYY.org |publisher=Associated Press |language=en-US}}

{{Reflist}}

• Greenwood, David. Antimicrobial Drugs: Chronicle of a twentieth century medical triumph (Oxford University Press, 2008) [https://global.oup.com/academic/product/antimicrobial-drugs-9780199534845?cc=us&lang=en&# summary]

• {{cite journal | vauthors = Kingston W | title = Streptomycin, Schatz v. Waksman, and the balance of credit for discovery | journal = Journal of the History of Medicine and Allied Sciences | volume = 59 | issue = 3 | pages = 441–462 | date = July 2004 | pmid = 15270337 | doi = 10.1093/jhmas/jrh091 | s2cid = 27465970 }}
• {{Cite news | vauthors = Mistiaen V |date=November 2, 2002 |title=Time, and the great healer |newspaper=The Guardian |url=https://www.theguardian.com/weekend/story/0,3605,823114,00.html }}. The history behind the discovery of streptomycin.
• {{cite web | url = https://www.nytimes.com/2012/06/12/science/notebooks-shed-light-on-an-antibiotic-discovery-and-a-mentors-betrayal.html | title = Notebooks Shed Light on an Antibiotic's Contested Discovery | work = The New York Times | date = June 12, 2012 | vauthors = Pringle P }}
• {{cite web | author = Office of Prevention, Pesticides And Toxic Substances | id = EPA-738-F-92-009 | title = Streptomycin and Streptomycin Sulfate Pesticide Reregistration | work = R.E.D. Facts | url = https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/fs_PC-006306_1-Sep-92.pdf | date = September 1992 | publisher = United States Environmental Protection Agency }}

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