Lack of in Vitro Inactivation of Tobramycin by Imipenem/Cilastatin

Abstract

OBJECTIVE: Inactivation of aminoglycosides by beta-lactam antimicrobials both in vitro and in vivo has been documented. Such an interaction has not previously been documented between carbapenems and aminoglycosides. Examination of serum concentrations of tobramycin in a patient receiving both agents suggested that this interaction might exist. The purpose of this study was to look at this question in an in vitro model. METHODS: Low concentrations of tobramycin (10 μg/mL) were incubated with imipenem/cilastatin (concentrations of 10, 20, and 40 μg/mL) in human serum at 37°C. Aliquots of these solutions were withdrawn at 0, 6, 24, 72, and 120 hours and assayed for tobramycin concentrations using a fluorescence polarization immunoassay. Aliquots of tobramycin 10 μg/mL and carbenicillin 200 μg/mL were analyzed in the same manner, as a positive control. High concentrations of tobramycin (800 μg/mL) and imipenem (5000 μg/mL)/cilastatin were incubated together at 21°C and sampled at 0, 6, 24, and 72 hours for tobramycin concentrations. RESULTS: The degradation rates for low-concentration tobramycin and the various concentrations of imipenem/cilastatin were not statistically different from those of the controlled incubations. In contrast, carbenicillin significantly enhanced the degradation rate of tobramycin at this concentration (half-life 72 hours and a 34 percent loss at 24 hours, p=0.0028). Higher in vitro concentrations of imipenem (5000 μg/mL)/cilastatin and tobramycin (800 μg/mL) resulted in significant, but moderate degradation over controlled incubations (half-life 80 hours and 10 percent loss at 12 hours, p=0.0031). CONCLUSIONS: These results suggest that inactivation of tobramycin is not a problem at common clinically achievable imipenem serum concentrations in patients.