Streptomycin

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Streptomycin
Clinical data
Other namesS/STR/STS[1]
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intramuscular, intravenous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability84% to 88% IM (est.)[2] 0% by mouth
Elimination half-life5 to 6 hours
ExcretionKidney
Identifiers
  • 5-(2,4-diguanidino-
    3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl)
    -3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl
    -tetrahydrofuran-3-carbaldehyde
JSmol)
Melting point12 °C (54 °F) [citation needed]
SMILES
  • CC1C(C(C(O1)OC2C(C(C(C(C2O)O)N=C(N)N)O)N=C(N)N)OC3C(C(C(C(O3)CO)O)O)NC)(C=O)O
  • InChI=1S/C21H39N7O12/c1-5-21(36,4-30)16(40-17-9(26-2)13(34)10(31)6(3-29)38-17)18(37-5)39-15-8(28-20(24)25)11(32)7(27-19(22)23)12(33)14(15)35/h4-18,26,29,31-36H,3H2,1-2H3,(H4,22,23,27)(H4,24,25,28)/t5-,6-,7+,8-,9-,10-,11+,12-,13-,14+,15+,16-,17-,18-,21+/m0/s1 checkY
  • Key:UCSJYZPVAKXKNQ-HZYVHMACSA-N checkY
 ☒NcheckY (what is this?)  (verify)
Look up streptomycin in Wiktionary, the free dictionary.

Streptomycin is an

muscle.[3]

Common side effects include

bacterial death.[3]

Albert Schatz first isolated streptomycin in 1943 from Streptomyces griseus.[5][6] It is on the World Health Organization's List of Essential Medicines.[7] The World Health Organization classifies it as critically important for human medicine.[8]

Uses

Medication

Streptomycin is traditionally given

intravenously.[2]

Pesticide

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.[10] 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.[11]

Cell culture

Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.[12]

Protein purification

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.[13]

Side effects

The most concerning side effects, as with other

aminoglycosides, are kidney toxicity and ear toxicity.[14] 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.[15]

Common side effects include vertigo, vomiting, numbness of the face, fever, and rash. Fever and rashes may result from persistent use.[citation needed]

Use is not recommended during pregnancy.[3] Congenital deafness has been reported in children whose mothers received streptomycin during pregnancy.[3] Use appears to be okay while breastfeeding.[4]

It is not recommended in people with myasthenia gravis.[4]

Mechanism of action

Streptomycin functions as a

mRNA strand. This results in an unstable ribosomal-mRNA complex, leading to premature stopping of protein synthesis, leading to cell death.[17] As human and bacteria both have ribosomes, streptomycin has significant side effects in humans. At low concentrations, however, streptomycin inhibits only bacterial growth.[18]

Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria,[19] and is therefore a useful broad-spectrum antibiotic.

History

Streptomycin was first isolated on October 19, 1943, by

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".[22] 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.[23][24][25][26][27] 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.[28] By the end of the settlement, Waksman would receive a 10% royalty, while Schatz got 3% and compensation for his missed royalties.[29] The rest of the lab shared the remaining 7% of the royalties, in which Bugie received 0.2%.[citation needed
]

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.[28] 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.[28] Bugie's contributions to Waksman's lab were great. In addition to her work on streptomycin, she also helped develop other antimicrobial substances,[30] had two peer-reviewed publications,[31][32] and researched the use of antimicrobials against plant pathogens,[33] among several other important contributions to the scientific field, particularly in regard to microbiology.

A scientist at Rutger's University making a streptomycin assay.

The Rutgers team reported streptomycin in the medical literature in January 1944.

H. Corwin Hinshaw of the Mayo Clinic with hopes of starting a human clinical trial of streptomycin in tuberculosis.[35]: 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.[35]: 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.[35]
: 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

Robert J. Dole, later Majority Leader of the United States Senate and presidential nominee—experienced a rapid and robust recovery.[36]

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946 through 1948 by the

double-blind nor placebo-controlled.[37] It is widely accepted to have been the first randomized curative trial.[38]

Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial

resistance to the drug.[37]

New Jersey

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.[39]

References

  1. ^ "Antibiotic abbreviations list". Retrieved June 22, 2023.
  2. ^
    S2CID 24111273. Archived
    from the original on October 5, 2011. Retrieved May 25, 2010.
  3. ^ a b c d e f g h i "Streptomycin Sulfate". The American Society of Health-System Pharmacists. Archived from the original on December 20, 2016. Retrieved December 8, 2016.
  4. ^
    ISBN 9789241547659
    .
  5. ISBN 9780191039621. Archived
    from the original on September 8, 2017.
  6. ISBN 9780123735812. Archived
    from the original on September 10, 2017.
  7. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ISBN 9789241515528
    . License: CC BY-NC-SA 3.0 IGO.
  9. ^ "Clinicians Tularemia". www.cdc.gov. September 2016. Retrieved November 8, 2017.
  10. S2CID 2380252
    .
  11. PMID 16560957
    .
  12. S2CID 29881502
    .
  13. OCLC 620957612
    .
  14. PMID 20627927
    .
  15. PMID 23123914
    .
  16. PMID 17967466
    .
  17. ^ Raymon LP (2011). COMLEX Level 1 Pharmacology Lecture Notes. Miami, FL: Kaplan, Inc. p. 181. CM4024K.
  18. ^ Voet D, Voet JG (2004). Biochemistry (3rd ed.).
    ISBN 978-0-471-19350-0
    .
  19. ^ Schantz JT, Ng KW (2004). A manual for primary human cell culture. World Scientific. p. 89.
  20. ^ Comroe JH (April 1978). "Pay dirt: the story of streptomycin. Part I. From Waksman to Waksman". The American Review of Respiratory Disease. 117 (4): 773–781.
    PMID 417651.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link
    )
  21. S2CID 27465970
    .
  22. ^ "All Nobel Prizes in Physiology or Medicine". NobelPrize.org. Archived from the original on June 9, 2017.
  23. ^ "Obiturary: Elizabeth Gregory / Did McCandless woman get fair shake for role in discovery of streptomycin?". old.post-gazette.com. Archived from the original on November 29, 2021. Retrieved November 7, 2021.
  24. ISBN 9780631164920. Archived
    from the original on September 10, 2017. Retrieved December 29, 2014.
  25. PMID 1882032
    .
  26. S2CID 27465970
    .
  27. ISBN 978-1620401989
    .
  28. ^ a b c "Elizabeth Bugie – the invisible woman in the discovery of streptomycin". The Scientista Foundation. Retrieved November 30, 2021.
  29. ^ "The Forgotten Women of the Antibiotics Race". Lady Science. July 22, 2021. Retrieved December 21, 2021.
  30. ISBN 9781555819545
    .
  31. PMID 16578091
    .
  32. PMID 16560863
    .
  33. S2CID 87534513
    .
  34. S2CID 33680180
    .
  35. ^
    ISBN 978-0316763806
    .
  36. ISBN 978-0-394-56260-5
    .
  37. ^
    PMID 10463905
    .
  38. S2CID 39878743
    .
  39. ^ "New Jersey gets official state microbe: Streptomyces griseus". WHYY.org. Associated Press. May 11, 2019.

Further reading

  • Greenwood, David. Antimicrobial Drugs: Chronicle of a twentieth century medical triumph (Oxford University Press, 2008) summary
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