Lack of in vitro inactivation of tobramycin by imipenem/cilastatin.
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 micrograms/mL) were incubated with imipenem/cilastatin (concentrations of 10, 20, and 40 micrograms/mL) in human serum at 37 degrees C. Aliquots of these solutions were withdrawn at 0, 6, 24, 72, and 120 hours and assayed for tobramycin concentrations using a fluorescence polarization immunoassay.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 micrograms/mL and carbenicillin 200 micrograms/mL were analyzed in the same manner, as a positive control. High concentrations of tobramycin (800 micrograms/mL) and imipenem (5000 micrograms/mL)/cilastatin were incubated together at 21 degrees 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 micrograms/mL)/cilastatin and tobramycin (800 micrograms/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.
Ariano
R E
RE
Department of Pharmacy, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
Kassum
D A
DA
Meatherall
R C
RC
Patrick
W D
WD
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002228:Carbenicillin / Q000494:pharmacology; D015377:Cilastatin / Q000494:pharmacology*; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D004347:Drug Interactions; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D066298:In Vitro Techniques; D014031:Tobramycin / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D002228:Carbenicillin; D014031:Tobramycin