Isepamicin (formerly SCH 21420 or 1-N-HAPA-gentamicin B) is a novel broad-spectrum aminoglycoside which possesses a high level of stability to aminoglycoside inactivating enzymes and low levels of toxicity to the kidney and inner ear. The only modifying enzymes capable of inactivating isepamicin are ANT(4')-I (staphylococci), ANT(4')-II and APH(3')-VI, in addition to resistance mediated by permeability mutations. The spectrum of isepamicin is most similar to that of amikacin, another aminoglycoside with high enzyme stability. Reviews of isepamicin activity demonstrate MIC90s ranging from 1.1 to 8.5 mg/L for members of the Enterobacteriaceae, slightly more potent than amikacin. Pseudomonas aeruginosa, Acinetobacter spp. and other pseudomonads had isepamicin consensus MIC90s of 7.8, 7.2 and 6.8 mg/ml, respectively. Staphylococci were generally very susceptible to isepamicin (MIC90s 0.5-6.9 mg/L), but enterococci and Streptococcus spp. were resistant (MIC90s > or = 64 mg/L), as were anaerobes, Xanthomonas (Stenotrophomonas) maltophilia, pathogenic Neisseria spp., Flavobacterium spp., Pseudomonas (Burkholderia) cepacia, Alcaligenes spp. and Vibrio spp. Additional studies of isepamicin microbiology revealed: 1) MICs were adversely influenced by elevated divalent cation content of the medium; 2) minimum inoculum effects were observed by using elevated concentrations; 3) bactericidal action and concentration dependent killing was the rule; 4) excellent stability in the presence of high beta-lactam co-drug concentrations was documented in several studies; 5) predictable synergistic or additive interactions with broad spectrum antimicrobial agents such as cephalosporins, penicillins, carbapenems and fluoroquinolones was observed by numerous investigators; and 6) in vitro susceptibility testing criteria (National Committee for Clinical Laboratory Standards) and quality control guidelines are established for routine clinical use. Isepamicin's antimicrobial qualities position it as a potential alternative aminoglycoside in hospitals or in geographical areas where resistance to existing aminoglycosides has emerged. The wider stability of isepamicin to contemporary aminoglycoside inactivating enzymes, its predictable pharmacokinetics, lower toxicity risks and enhanced activity (synergy) with other broad spectrum antimicrobial agents, will make isepamicin a valuable addition to the antimicrobial armamentarium in areas where ACC(6') enzymes are prevalent (Europe, Latin America, Western Pacific) and amikacin has become less efficacious.