Systematic (IUPAC) name
Clinical data
AHFS/ monograph
MedlinePlus a682275
  • D
IV, Ophthalmic, IM, topical
Pharmacokinetic data
Bioavailability limited oral bioavailability
Protein binding 0-10%
Half-life 2 hrs
Excretion renal
1403-66-3 7pxY
D06AX07 J01GB03 S01AA11 S02AA14 S03AA06 QA07AA91 QG01AA91 QG51AA04 QJ51GB03
PubChem CID 3467
IUPHAR ligand 2427
DrugBank DB00798 7pxN
ChemSpider 390067 7pxY
KEGG D08013 7pxY
ChEBI CHEBI:27412 7pxY
ChEMBL CHEMBL195892 7pxY
Chemical data
Formula C21H43N5O7
477.596 g/mol
 14pxN (what is this?)  (verify)

Gentamicin is an aminoglycoside antibiotic composed of a mixture of related gentamicin components and fractions and is used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms.[1] However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis, or Legionella pneumophila. Gentamicin is also ototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use.[1]

It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the environment (water and soil). To highlight their specific biological origins, gentamicin and other related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin, retymicin) generally have their spellings ending in ~micin and not in ~mycin. Gentamicin is a bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis.

Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is because it is not absorbed to any appreciable extent from the small intestine. It is administered intravenously, intramuscularly or topically to treat infections. It appears to be completely eliminated unchanged in the urine. Urine must be collected for many days to recover all of a given dose because the drug binds avidly to certain tissues.

E. coli has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use gentamicin for empirical therapy has led to increased use of alternative broad-spectrum antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial infections by MRSA and other so-called "superbugs".[1]

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. It is used during orthopaedic surgery when high temperatures are required for the setting of cements (e.g. hip replacements).[2]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[3]

Medical uses

Active against a wide range of human bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus.[4] Gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis, its relatives, and Francisella tularensis (the organism responsible for tularemia seen often in hunters and/or trappers).[5] Some Enterobacteriaceae, Pseudomonas spp., enterococci, Staphylococcus aureus and other staphylococci are resistant to gentamicin sulfate, to varying degrees.[6]

Optimal use in neonates In neonates, evidence suggests that the use of large-dose, extended interval genta regimens are more likely to achieve optimum peak and trough concentration when compared to the traditional multiple daily dose regimens. In addition, the adjustment of dose and dosage interval according to gestational age (GA) and birth weight is found to be suitable for preterm neonates . Based on these rationales, several neonatal genta dosing regimens have been proposed. However, there is a wide variety among these protocols (Darmstadt et al., 2008). There is evidence of a relationship between serum genta levels, efficacy and incidence of toxic events. Available data on the use of genta in neonates suggested that extended dosing intervals and higher dose >= 4 mg/ kg confer favorable pharmacokinetic profile (high peak & low trough level). This provides the basis for potential enhancement of therapeutic efficacy and reduces toxicity. (Darmstadt et al., 2008; Daniel, Elsbeth and Arwen, 2009 ). Khaled Alfaify, Ahmed Ali and, Mohammad Farouq " Pharmacokinetic approach for optimizing the dose of Gentamicin in Saudi Neonates during the first week of life "

Side effects

Aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause permanent loss of equilibrioception, caused by damage to the vestibular apparatus of the inner ear, usually if taken at high doses or for prolonged periods of time, but there are well documented cases in which gentamicin completely destroyed the vestibular apparatus after three to five days.[citation needed] A small number of affected individuals have a normally harmless mutation in their mitochondrial DNA encoding the 12S ribosomal RNA (m.1555 A>G), that allows the gentamicin to affect their cells.[7] The cells of the ear are particularly sensitive to this, sometimes causing complete hearing loss.[8] However, gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease, to disable the vestibular apparatus. These side effects are most common when the drug is administered via drops directly to the ear.

Side effects of gentamicin toxicity vary from patient to patient. Side effects may become apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin toxicity include:

  • Balance difficulty
  • Bouncing, unsteady vision
  • Ringing in the ears (tinnitus)
  • Difficulty multi-tasking, particularly when standing

Gentamicin is nephrotoxic. Risk factors for aminoglycoside nephrotoxicity include patient factors such as:

  • increased age
  • reduced renal function
  • pregnancy
  • hypothyroidism
  • hepatic dysfunction
  • volume depletion
  • metabolic acidosis
  • concurrent use of other drugs: vancomycin, NSAIDs, cisplatin, cyclosporin, cephalosporin, diuretics
  • Concurrent use of iodinated contrast agents

Treatment factors can also affect toxicity. Important factors such as dose, frequency, levels and duration of therapy can affect level of toxicity.

Prevention of nephrotoxicity includes judicouss use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses. Gentamicin is usually dosed by ideal body weight. Various formulae exist for calculating gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment to individualize therapy and prevent excess exposure.[9]

Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting in acute tubular necrosis which can lead to acute renal failure.[10]

Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion, depression, disorientation and visual hallucinations.[11] Immediate professional help should be sought if any of these symptoms or others appear after administration of aminoglycosides. General medical practitioners should refer patients with such symptoms to an otolaryngologist, commonly known as an 'ear, nose, and throat doctor', for comprehensive tests.

A number of factors and determinants should be taken into account when using gentamicin, including differentiation between empirical and directed therapy which will affect dosage and treatment period.[1] Many medical practitioners freely administer gentamicin as an antibiotic without advising patients of the severe and permanent potential ramifications of its use. Gentamicin is well known to be a cheap, low-cost yet old medicine when compared with modern alternatives, and is typically US$3–6 per dosage less than modern alternatives.

Many people recover from gentamicin toxicity naturally over time if the drug is discontinued, but they recover slowly and usually incompletely.[citation needed] Sometimes the toxicity of gentamicin can still increase over months after the last dose. Upon cessation of gentamicin therapy symptoms such as tinnitus and imbalance may become less pronounced. Sensori-neural hearing loss caused by gentamicin toxicity is permanent however.

Mechanism of action

Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis. This mechanism of action is similar to other aminoglycosides[12]

Gentamicin C complex and related components

Gentamicin is composed of a number of related gentamicin components and fractions which have varying degrees of antimicrobial potency.[13] 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.[14] 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.[15]

Production and usage in research

File:Gentamicin for injection.jpg
Gentamicin for injection

Gentamicin is produced by the fermentation of Micromonospora purpurea. It was discovered in 1963 by Weinstein, Wagman et al. at Schering Corporation in Bloomfield, N.J. working with source material (soil samples) provided by Rico Woyciesjes.[16] Subsequently it was purified and the structures of its three components determined by Cooper, et al., also at the Schering Corporation. It was initially used as a topical treatment for burns at the Atlanta and San Antonio burn units and was introduced into IV usage in 1971. It remains a mainstay for use in sepsis.

Gentamicin is also used in molecular biology research as an antibacterial agent in tissue and cell culture, to prevent contamination of sterile cultures.


  1. ^ a b c d Moulds, Robert and Jeyasingham, Melanie (October 2010). "Gentamicin: a great way to start". Australian Prescriber (33): 134–135. 
  2. ^ Hendriks JGE, van Horn JR, van der Mei HC, and Busscher, HJ (2004). "Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection". Biomaterials 25 (3): 545–556. PMID 14585704. doi:10.1016/S0142-9612(03)00554-4. 
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ Gentamicin: Drug Information Provided by Lexi-Comp: Merck Manual Professional
  5. ^ Goljan, Edward F. (2011). Rapid Review Pathology 3rd ed. Philadelphia, PA: Elsevier. p. 241. ISBN 978-0-323-08438-3. 
  6. ^ "Gentamicin spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 15 May 2012. 
  7. ^ PMID 20301595 (PubMed)
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  8. ^ Gentamicin Toxicity at the American Hearing Research Foundation
  9. ^ Lopez-Novoa, Jose (2011). "New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view.". Kidney International 79: 33–45. PMID 20861826. doi:10.1038/ki.2010.337. Retrieved 2014-09-30. 
  10. ^ Sundin DP, Sandoval R, Molitoris BA: Gentamicin Inhibits Renal Protein and Phospholipid Metabolism in Rats: Implications Involving Intracellular Trafficking. J Am Soc Nephrol 12:114-123, 2001
  11. ^ AJ Giannini, HR Black. Psychiatric, Psychogenic and Somatopsychic Disorders Handbook. Garden City, NY. Medical Examination Publishing Co.,1978. Pp.136-137. ISBN 0-87488-596-5.
  12. ^
  13. ^ Weinstein, Marvin J. "Biological Activity of the Antibiotic Components of the Gentamicin Complex." Journal of Bacteriology 94.3 (1967): 789-90. Web. 15 Oct. 2013.
  14. ^ Vydrin, A. F. "Component Composition of Gentamicin Sulfate Preparations." Pharmaceutical Chemistry Journal 37.8 (2003): 448-49. Web. 15 Oct. 2013.
  15. ^ Isoherranen, Nina, and Eran Lavy. "Pharmacokinetics of Gentamicin C1, C1a, and C2 in Beagles after a Single Intravenous Dose." Antimicrobial Agents and Chemotherapy 44.6 (2000): 1443-447. Web.
  16. ^ Weinstein, Marvin; Wagman (1963). "Gentamicin, A New Antimicrobial Complex from Micromonospora". J Med Chem 6: 463–464. doi:10.1021/jm00340a034.