ANTIMICROBIAL: Gentamicin
CLASS: Aminoglycoside
SOME OTHER ANTIMICROBIALS IN THE SAME CLASS: Tobramycin, Amikacin, Neomycin, Streptomycin (the first aminoglycoside and also the one with the best anti-mycobacterial activity.) Note not all “mycins” are aminoglycosides, with erythromycin (macrolide) and vancomycin (glycopeptide) being the ones most commonly mislabelled.
ORIGINS: Gentamicin was discovered in 1963 by Weinstein and colleagues from the soil fungus Micromonospora purpura (of the Actinomycete group). Introduced commercially in 1969.
MECHANISM OF ACTION: Gentamicin inhibits bacterial protein synthesis mainly through binding with the 30S ribosomal subunit, and acts through two different mechanisms. In one mechanism, gentamicin can interfere with the correct amino acid polymerization and elongation. This mechanism takes place at high concentrations. Another mechanism predominates at low concentrations in which amino acid codons are misread by tRNA and proofreading is impaired. This leads to incorrect amino acid sequencing and nonsense proteins. Complex? Yes, I agree!
ROUTE OF ADMINISTRATION: Intra-venous, topical, and occasionally intra-muscular. (Poor oral bioavailability)
MAIN CLINICAL USES: Gram negative sepsis. Used in conjuction with a beta-lactam for some types of Infective Endocarditis. Occasionally used for surgical prophylaxis. Topical use in eye and ear infections.
MAIN SIDE EFFECTS OF NOTE: Renal toxicity, Ototoxicity. Ototoxicity (to be more specific vestibular toxicity) in particular is under-appreciated. Both renal toxicity and ototoxicity correlate loosely with total drug exposure, with some patients having documente problems after just one single large dose.
RESISTANCE: Multi-factorial. There are three main mechanisms of aminoglycoside resistance: production of aminoglycoside modifying enzymes, reduced uptake or decreased cell permeability, or alterations at the ribosomal binding sites.
OTHER POINTS OF NOTE: Mainly due to toxicity concerns, movement nowadays to just use gentamicin for 1-2 days in the initial treatment of a patient with sepsis, usually in conjunction with a beta-lactam. prolonged use without very good reason generally now frowned upon.