This review of aminoglycoside pharmacology will appear in two parts. The first segment summarizes general information applicable to all agents, such as aspects of absorption, distribution, and clearance. The subsequent article will focus on specific agents currently in use in clinical practice: gentamicin, tobramycin, netilmicin, amikacin, streptomycin, and kanamycin, highlighting toxicities and pharmacokinetic-based dosing strategies.
Embedded in the history of antimicrobial agents with the discovery of streptomycin in 1944, the aminoglycosides remain a mainstay of contemporary antibiotic therapy. Noteworthy features include rapid bactericidal activity against aerobic gram-negative organisms as well as additive or synergistic activity when coadministered with beta-lactam agents. These positive attributes are offset by limited penetration into various body fluids and tissues, and dose (concentration) related renal and ototoxicity. Despite the proliferation of safer beta-lactam compounds with expanded antimicrobial spectrums, the aminoglycosides are still initial drugs of choice for most life-threatening, aerobic, gram-negative infections. Used in combination with anti-pseudomonal penicillins, the aminoglycosides are the agents of choice for empiric therapy of fever in the neutropenic host or documented tissue infection with Pseudomonas aeruginosa.