Aminoglycoside Inactivation by Penicillins and Cephalosporins and its Impact on Drug-Level Monitoring

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Abstract
The degree of in vitro inactivation of gentamicin, tobramycin, and amikacin by various penicillins and cephalosporins was investigated. Serum samples were prepared that contained one aminoglycoside and one penicillin or cephalosporin. Each aminoglycoside was combined with each of the following: penicillin, ampicillin, nafcillin, carbenicillin, ticarcillin, cephapirin, cefazolin, cefoxitin, and cefamandole. Each sample contained a final concentration of 10 μ/ml of gentamicin or tobramycin, or 35 μ/ml of amikacin, with 400 μg/ml of the β-lactam antibiotic. Control samples containing only the aminoglycoside were used for comparison. Half of each mixture was frozen at −20°C and the remainder was left at room temperature for 24 hours. The samples were assayed for aminoglycoside content by a radioimmunoassay and each combination was compared with its control value. Based on the results, the β-lactams can be divided into three groups: (1) cefazolin and cefamandole, which cause little inactivation; (2) nafcillin, cephapirin, and cefoxitin, which cause moderate inactivation; and (3) penicillin, ampicillin, carbenicillin, and ticarcillin, which cause marked inactivation. In general, tobramycin was the most reactive of the three aminoglycosides studied and amikacin the most stable. The frozen samples were much less affected than those left at room temperature. Freezing samples, if there will be a delay in assaying, and choosing aminoglycoside sampling times when the β-lactam concentration is at a trough are recommended to minimize spurious aminoglycoside level determinations due to in vitro inactivation.