ANTIBACTERIAL ACTIVITIES, NEPHROTOXICITY, AND OTOTOXICITY OF A NEW AMINOGLYCOSIDE, WIN-42122-2

Win 42122-2 is a new aminoglycoside antibiotic obtained from a mutant strain of Micromonospora purpurea. In vitro and in vivo comparisons of Win 42122-2 with gentamicin and amikacin revealed that Win 42122-2 generally was less active than gentamicin against Pseudomonas and many Enterobacteriacae, especially Klebsiella and indole-negative Proteus. Against most gentamicin-susceptible isolates, Win 42122-2 was more active than amikacin. Gentamicin-resistant clinical isolates were ususally resistant to Win 42122-2, although it was active against certain gentamicin-resistant organisms, depending upon the aminoglycoside-modifying enzymes harbored by the organism. However, Win 42122-2 was markedly less toxic than gentamicin in subacute nephrotoxicity studies in rats, ototoxicity experiments in guinea pigs, and ataxia determinations in cats. This series of antibacterial determinations and toxicity evaluations indicated that the reduced toxicity of the antibiotic may be sufficient to provide an improved therapeutic ratio over gentamicin and other aminoglycosides, even though Win 42122-2 is less potent than gentamicin against some bacteria.