Growth kinetics of multiple Acinetobacter baumannii resistotype after meropenem-based antibiotic combination exposure

Abstract

Background: Carbapenems are the treatment of choice for multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections, but the emergence of carbapenem-resistant A. baumannii (CRAB) has rendered it ineffective in the vast majority of cases. Combination therapy has grown in popularity over the last decade; this study aims to analyze A.baumannii growth kinetics after exposure to meropenem and ampicillin-sulbactam compared with meropenem and amikacin antibiotic combinations in clinically relevant concentrations.  Methods: This experimental laboratory study was conducted on the A. baumannii ATCC 19606 isolate and three clinical isolates that were intermediate or resistant to tested antibiotics. Meropenem and ampicillin-sulbactam, as well as meropenem and amikacin, were tested at four different concentrations against isolates. Turbidity measurements were taken at predetermined time points of 0, 1, 2, 4, 6, 8, and 24 hours following exposure; bacterial concentration was enumerated using the agar plate method, with the results plotted in a time-kill curve.   Results: A bactericidal effect was achieved in isolates that were intermediate to ampicillin-sulbactam and resistant to meropenem after the administration of meropenem and ampicillin-sulbactam combination with a concentration of 4 µg/ml and 16/8 µg/ml, respectively. The combination of meropenem and ampicillin-sulbactam demonstrated bacteriostatic activity against isolates that were resistant to both antibiotics. Isolates treated with resistant antibiotics showed an increased growth rate compared to the growth control.  Conclusion: The combination of meropenem and ampicillin-sulbactam could be a promising combination therapy in treating CRAB infections. The mechanism and degree of antibiotic resistance in the isolates affect the efficacy of antibiotic combinations; further research is needed to corroborate the findings of this study.