Comparative aminoglycoside inactivation by beta-lactam antibiotics. Effects of a cephalosporin and six penicillins on five aminoglycosides

Abstract

Gentamicin, tobramycin, netilmicin, kanamycin and amikacin were evaluated over time for biologic activity in human serum, in combination with 6 beta-lactams. Simple addition of aminoglycoside and 250 micrograms/ml penicillin produced aminoglycoside inactivation at 8 approximately 48 hours. However, all beta-lactam antibiotics exhibited decay in human serum at 37 degrees C, even when present as a single component. All aminoglycosides could be inactivated by penicillins but differed markedly in their susceptibility. Amikacin, at 20 micrograms/ml, was the least inactivated by any penicillin; netilmicin, at 10 micrograms/ml, was the next least inactivated. Tobramycin had pronounced loss of biological activity exceeding that of any aminoglycoside, appearing as early as 8 hours. The ability of the various penicillins to produce aminoglycoside inactivation, in approximate descending order, was; carbenicillin, ticarcillin, penicillin G, oxacillin, methicillin, ampicillin. Cephalothin produced minimal inactivation. Aminoglycoside inactivation also occurred at 25 degrees C, and with many samples stored at 4 degrees C, although at proportionately slower rates. For samples stored at -20 degrees C, only tobramycin had substantial loss of activity. These data indicate that adequate handling and prompt assay of the specimen are important.