Gentamicin

Source: Wikipedia, the free encyclopedia.

Gentamicin
Clinical data
Pronunciation/ˌdʒɛntəˈmaɪsən/
Trade namesCidomycin, Genticyn, Garamycin, others
AHFS/Drugs.comMonograph
MedlinePlusa682275
License data
Pregnancy
category
QJ51GB03 (WHO)
Legal status
Legal status
  • US: WARNING[2]
  • EU: Rx-only[3]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilitylimited bioavailability by mouth
Protein binding0–10%
Elimination half-life2 h
ExcretionKidney
Identifiers
  • (3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-
    diamino-3-{[(2R,3R,6S)-
    3-amino-6-[(1R)-
    1-(methylamino)ethyl]oxan-2-yl]oxy}-
    2-hydroxycyclohexyl]oxy}-5-methyl-
    4-(methylamino)oxane-3,5-diol
JSmol)
  • O[C@]3(C)[C@H](NC)[C@@H](O)[C@@H](O[C@H]2[C@H](N)C[C@H](N)[C@@H](O[C@H]1O[C@H](C(NC)C)CC[C@H]1N)[C@@H]2O)OC3
  • InChI=1S/C21H43N5O7/c1-9(25-3)13-6-5-10(22)19(31-13)32-16-11(23)7-12(24)17(14(16)27)33-20-15(28)18(26-4)21(2,29)8-30-20/h9-20,25-29H,5-8,22-24H2,1-4H3/t9?,10-,11+,12-,13+,14+,15-,16-,17+,18-,19-,20-,21+/m1/s1 checkY
  • Key:CEAZRRDELHUEMR-URQXQFDESA-N checkY
 ☒NcheckY (what is this?)  (verify)

Gentamicin is an

bacterial cultures determine what specific antibiotics the infection is sensitive to.[6] The dose required should be monitored by blood testing.[4]

Gentamicin can cause

kills the bacteria.[4]

Gentamicin is naturally produced by the bacterium

generic medication.[12]

Medical uses

Gentamicin is active against a wide range of bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia, and the Gram-positive Staphylococcus.[13] Gentamicin is used in the treatment of respiratory tract infections, urinary tract infections, blood, bone and soft tissue infections of these susceptible bacteria.[14]

There is insufficient evidence to support gentamicin as the first line treatment of

endotoxin found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis (responsible for plague), its relatives, and Francisella tularensis (the organism responsible for tularemia often seen in hunters and trappers).[16]

Some Enterobacteriaceae, Pseudomonas spp., Enterococcus spp., Staphylococcus aureus and other Staphylococcus spp. have varying degrees of resistance to gentamicin.[17]

Special populations

Pregnancy and breastfeeding

Gentamicin is not recommended in pregnancy unless the benefits outweigh the risks for the mother. Gentamicin can cross the

newborn.[14]

The safety and efficacy for gentamicin in nursing mothers has not been established. Detectable gentamicin levels are found in human breast milk and in nursing babies.[14]

Elderly

In the elderly,

renal function should be assessed before beginning therapy as well as during treatment due to a decline in glomerular filtration rate. Gentamicin levels in the body can remain higher for a longer period of time in this population. Gentamicin should be used cautiously in persons with renal, auditory, vestibular, or neuromuscular dysfunction.[13]

Children

Gentamicin may not be appropriate to use in children, including babies. Studies have shown higher

Kidney function should be checked periodically during therapy. Long-term effects of treatment can include hearing loss and balance problems. Hypocalcemia, hypokalemia, and muscle weakness have been reported when used by injection.[13]

Contraindications

Gentamicin should not be used if a person has a history of

aminoglycosides.[14] Greater care is required in people with myasthenia gravis and other neuromuscular disorders as there is a risk of worsening weakness.[4] Gentamicin should also be avoided when prescribing empirical antibiotics in the setting of possible infant botulism (Ampicillin with Gentamicin is commonly used as empiric therapy in infants) also due to worsening of neuromuscular function.[19]

Adverse effects

Adverse effects of gentamicin can range from less severe reactions, such as nausea and vomiting, to more severe reactions including:[13]

Nephrotoxicity and ototoxicity are thought to be dose related with higher doses causing greater chance of toxicity.[13] These two toxicities may have delayed presentation, sometimes not appearing until after completing treatment.[13]

Kidney damage

amphotericin, iodide contrast media, and vancomycin.[20]

Factors that increase risk of nephrotoxicity include:[20]

Kidney dysfunction is monitored by measuring creatinine in the blood, electrolyte levels, urine output, presence of protein in the urine, and concentrations of other chemicals, such as urea, in the blood.[20]

Inner ear

About 11% of the population who receives aminoglycosides experience damage to their inner ear.[21] The common symptoms of inner ear damage include tinnitus, hearing loss, vertigo, trouble with coordination, and dizziness.[22] Chronic use of gentamicin can affect two areas of the ears. First, damage of the inner ear hair cells can result in irreversible hearing loss. Second, damage to the inner ear vestibular apparatus can lead to balance problems.[22] To reduce the risk of ototoxicity during treatment, it is recommended to stay hydrated.[13]

Factors that increase the risk of inner ear damage include:[13][14]

Pharmacology

Mechanism of action

Gentamicin is a

proteins that recognize stop codons. At this secondary site, gentamicin is believed to preclude interactions of the ribosome with ribosome recycling factors, causing the two subunits of the ribosome to stay complexed even after translation completes. This creates a pool of inactive ribosomes that can no longer re-initiate and translate new proteins.[27]

Chemistry

Structure

Since gentamicin is derived from the species Micromonospora, the backbone for this antibiotic is the aminocyclitol 2-deoxystreptamine.[28][29] This six carbon ring is substituted at the carbon positions 4 and 6 by the amino sugar molecules cyclic purpurosamine and garosamine, respectively.[30][28] The gentamicin complex, is differentiated into five major components (C1, C1a, C2, C2a, C2b) and multiple minor components by substitution at the 6' carbon of the purpurosamine unit indicated in the image to the right by R1 and R2.[30][28][31][32] The R1 and R2 can have the follow substitutions for some of the species in the gentamicin complex.[30][33][29]

Major component
C complex R1 R2
C1
Methyl
group
Methyl
group
C1a Hydrogen Hydrogen
C2 Hydrogen
Methyl
group
C2a Hydrogen
Methyl
group
C2b
Methyl
group		 Hydrogen

Components

Gentamicin is composed of a number of related gentamicin components and fractions which have varying degrees of antimicrobial potency.[34] The main components of gentamicin include members of the gentamicin C complex: gentamicin C1, gentamicin C1a, and gentamicin C2 which compose approximately 80% of gentamicin and have been found to have the highest antibacterial activity. Gentamicin A, B, X, and a few others make up the remaining 20% of gentamicin and have lower antibiotic activity than the gentamicin C complex.[32] The exact composition of a given sample or lot of gentamicin is not well defined, and the level of gentamicin C components or other components in gentamicin may differ from lot-to-lot depending on the gentamicin manufacturer or manufacturing process. Because of this lot-to-lot variability, it can be difficult to study various properties of gentamicin including pharmacokinetics and microorganism susceptibility if there is an unknown combination of chemically related but different compounds.[35]

Biosynthesis

The complete

Glucose-6-phosphate being dephopsphorylated, transaminated, dehydrogenated and finally glycosylated with D-glucosamine to generate paromamine inside Micromonospora echinospora.[30] The addition of D-xylose leads to the first intermediate of the gentamicin C complex pathway, gentamicin A2.[30][38] Gentamicin A2 is C-methylated and epimerized into gentamicin X2, the first branch point of this biosynthesis pathway[38]

When X2 is acted on by the

dehydroxylated and epimerized to first component of the gentamicin C complex, gentamicin C2a which then undergoes an epimerization by GenB2 and then a N-methylation by an unconfirmed gene to form the final product in this branch point, gentamicin C1.[38][41][30][42]

When X2 bypasses GenK and is directly

dehydroxylated into the first component of the gentamicin C complex for this branch, gentamicin C1a via a catalytic reaction with GenB4.[42] C1a then undergoes an N-methylation by an unconfirmed enzyme to form the final component, gentamicin C2b.[41][38][30][42]

Fermentation

Gentamicin is only synthesized via submerged

metal ions (cobalt and a few others at low concentration), various vitamins (mostly B vitamins), purine and pyrimidine bases are also supplemented into the growth medium to increase gentamicin production, but the margin of increase is dependent on the species of Micromonospora and the other components in the growth medium.[30][36] With all of these aforementioned additives, pH and aeration are key determining factors for the amount of gentamicin produced.[30][33] A range of pH from 6.8 to 7.5 is used for gentamicin biosynthesis and the aeration is determined by independent experimentation reliant on type of growth medium and species of Micromonospora.[30][33]

History

Gentamicin for injection

Gentamicin is produced by the fermentation of

Gentian Violet and hence this was why Gentamicin took then name it did. Subsequently, it was purified and the structures of its three components were determined by Cooper, et al., also at the Schering Corporation. It was initially used as a topical treatment for burns at burn units in Atlanta and San Antonio and was introduced into IV usage in 1971. It remains a mainstay for use in sepsis.[citation needed
]

It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the environment (water and soil). According to the American Medical Association Committee on Generic Names, antibiotics not produced by Streptomyces should not use y in the ending of the name, and to highlight their specific biological origins, gentamicin and other related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin, and retymicin) have their spellings ending in ~micin and not in ~mycin.[43]

Research

Gentamicin is also used in molecular biology research as an antibacterial agent in tissue and cell culture, to prevent contamination of sterile cultures. Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving, which makes it particularly useful in the preparation of some microbiological growth media.[citation needed]

References

  1. ^ a b "Gentamicin Use During Pregnancy". Drugs.com. 28 February 2019. Retrieved 11 February 2020.
  2. FDA
    . Retrieved 22 October 2023.
  3. ^ "Active substance: gentamicin (systemic use)" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 26 November 2020.
  4. ^ a b c d e f g h i j k l m "Gentamicin sulfate". The American Society of Health-System Pharmacists. Archived from the original on 16 August 2015. Retrieved 15 August 2015.
  5. ISBN 9781483193915. Archived
    from the original on 22 December 2015.
  6. doi:10.18773/austprescr.2010.062
    .
  7. ^ "Gentamicin use while breastfeeding". Archived from the original on 6 September 2015. Retrieved 15 August 2015.
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  10. hdl:10665/325771
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  11. ISBN 9789241515528
    . License: CC BY-NC-SA 3.0 IGO.
  12. ISBN 9780323340267. Archived
    from the original on 11 March 2016.
  13. ^ a b c d e f g h i "Gentamicin" (PDF). Baxter Corporation. Archived from the original (PDF) on 4 March 2016. Retrieved 2 November 2015.
  14. ^ a b c d e "Gentamicin Injection USP" (PDF). Product Monograph. Sandoz Canada Inc. Archived from the original (PDF) on 12 April 2015. Retrieved 2 November 2015.
  15. PMID 25239090
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  16. ISBN 978-0-323-08438-3
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  17. ^ "Gentamicin spectrum of bacterial susceptibility and Resistance" (PDF). TOKU-E. Archived from the original (PDF) on 20 February 2015. Retrieved 15 May 2012.
  18. S2CID 23564581
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  19. S2CID 36001577
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  20. ^
    PMID 20861826
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  21. PMID 15831617
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  22. ^
    PMID 17266591
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  23. ^ "DrugBank-Gentamicin". Archived from the original on 4 October 2013.
  24. PMID 30139800
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  25. S2CID 9264620
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  26. ISBN 978-1-55581-184-6
    .
  27. S2CID 31576287
    .
  28. ^
    PMID 28620453
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  29. ^
    ISBN 978-0-470-74167-2.{{cite book}}: CS1 maint: location missing publisher (link
    )
  30. ^
    S2CID 83784820
    .
  31. ^
    PMID 4962848
    .
  32. ^
    S2CID 43731658
    .
  33. ^
    PMID 1092638
    .
  34. PMID 4962848
    .
  35. PMID 10817690
    .
  36. ^
    PMID 5487130
    .
  37. ^
    doi:10.1016/S0032-9592(02)00230-3
    .
  38. ^
    PMID 931800
    .
  39. PMID 23679096
    .
  40. PMID 23149679
    .
  41. ^
    PMID 24746560
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  42. ^
    PMID 32156271
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  43. PMID 4306977
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Further reading

External links

  • "Gentamicin". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Gentamicin&oldid=1219280416"