Selective inactivation of aminoglycosides by newer beta-lactam antibiotics

Combinations of aminoglycoside and beta-lactam antibiotics may act synergistically against certain microorganisms. However, aminoglycosides have been shown to interact chemically with certain beta-lactam antibiotics resulting in diminished activity of the aminoglycoside. Two beta-lactam antiotics, moxalactam and cefotaxime, as well as several other beta-lactams in current use, were studied for possible inactivation of gentamicin, tobramycin and amikacin. Aqueous mixtures of each of the three aminoglycosides plus a beta-lactam antibiotic (moxalactam, cefotaxime, cephalothin, carbenicillin, ticarcillin or penicillin) were prepared in ratios of 10:1 and 50:1 (beta-lactam: aminoglycoside). Gentamicin and tobramycin were markedly inactivated by carbenicillin and ticarcillin, and to a lesser degree by penicillin (only at the 50:1 ratio), but not by cephalothin, cefotaxime, or moxalactam. Conversely, amikacin was significantly inactivated by cephalothin and moxalactam, by ticarcillin only at a 50:1 ratio, and was not significantly inactivated by carbenicillin, penicillin, or cefotaxime. Thus, there were selective differences in the susceptibilities of the aminoglycosides to inactivation as well as differences in the propensities of certain beta-lactam antibiotics to cause inactivation.