Gentamicin

Gentamicin is an aminoglycoside antibiotic used to treat serious infections caused by certain Gram-negative bacteria and, in combination with other agents, some Gram-positive infections. It is effective against organisms such as Pseudomonas aeruginosa and Enterobacteriaceae and is often employed for severe systemic infections, including septicemia, complicated urinary tract infections, and intra-abdominal infections, typically in conjunction with beta-lactam antibiotics to broaden coverage and enhance bactericidal activity.

Mechanism of action and pharmacodynamics: Gentamicin binds irreversibly to the 30S ribosomal subunit, causing misreading of messenger RNA and disruption of protein synthesis. The resulting bactericidal effect is concentration-dependent, and a post-antibiotic effect may persist after drug levels fall, allowing once-daily or extended-interval dosing in some settings.

Pharmacokinetics and administration: The drug is usually given by parenteral routes (intravenous or intramuscular) because oral absorption is poor. It distributes mainly in extracellular fluid and is excreted largely unchanged by the kidneys. Dosing and duration are influenced by renal function, and monitoring of drug levels and kidney function is common to minimize toxicity.

Adverse effects and cautions: The most serious risks are nephrotoxicity and ototoxicity (affecting cochlear and vestibular function). Less common effects include neuromuscular blockade and hypersensitivity. Risk is higher with elevated trough levels, prolonged therapy, dehydration, existing kidney disease, advanced age, and concurrent nephrotoxic or ototoxic drugs (for example, loop diuretics). Use requires careful monitoring, especially in renal impairment and during pregnancy or lactation.

Resistance and history: Resistance mechanisms include aminoglycoside-modifying enzymes, altered ribosomal targets, and reduced uptake. Gentamicin was developed in the mid-20th century and has since become a staple in the management of serious Gram-negative infections, often as part of combination therapy.