Aminoglycosides — MOA & Use

Aminoglycosides (gentamicin, tobramycin, amikacin, neomycin, streptomycin) work by irreversibly binding to the 30S ribosomal subunit of bacteria, causing misreading of mRNA and production of aberrant proteins that damage the bacterial cell membrane. Unlike bacteriostatic drugs that merely slow growth, aminoglycosides are bactericidal — they directly kill bacteria. Their killing power is concentration-dependent: the higher the peak concentration above the minimum inhibitory concentration, the greater the bacterial kill. This is why extended-interval (once-daily) dosing is preferred over traditional divided dosing — a single large dose achieves a high peak that maximizes killing, then allows a drug-free interval to reduce toxicity. Primary indications include serious gram-negative infections: Pseudomonas aeruginosa, E. coli, Klebsiella, and Serratia. They're commonly used for sepsis, complicated UTIs, pneumonia from gram-negative organisms, and as synergy with beta-lactams or vancomycin for endocarditis. Aminoglycosides have poor oral absorption — they must be given IV or IM for systemic infections. Oral neomycin is an exception, used specifically for bowel sterilization before surgery or in hepatic encephalopathy because it stays in the gut lumen.