In Vitro Activities Of Ceftazidime/Avibactam Alone Or In Combination With Antibiotics Against Multi-Drug Resistant Acinetobacter baumannii Isolates

Abstract Objectives Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii are a growing problem because of the limited options for treatment. The number of antimicrobials that are currently being developed is still insufficient to control this global threat. Combination therapies of antibiotics with different antimicrobial mechanisms have been proposed as the best options for treating MDR A. baumannii infections. The objective of this study was to investigate the in vitro effectiveness of ceftazidime/avibactam alone or in combination with antibiotics against MDR A. baumannii isolates using time-kill assays. Methods Forty clinical MDR strains were screened and MIC and MBC of ceftazidime/avibactam, colistin, levofloxacin, meropenem, tigecycline, and tobramycin were determined by microbroth dilution method. The in vitro synergistic activities of ceftazidime/avibactam with antibiotics’ combinations were determined by time-kill assays at 1 x MIC and 4 x MIC against five MDR A. baumannii isolates. Results Based on MIC results, all isolates of A. baumannii were resistant to ceftazidime/avibactam, except forAB-5. All isolates were found to be resistant to meropenem and levofloxacin. At 4xMIC, all of the tested antibiotics showed bactericidal effect (≥3 log 10 killing). The synergistic activities of ceftazidime/avibactam + colistin, ceftazidime/avibactam + tobramycin and ceftazidime/avibactam + tigecycline combinations at 1xMIC were observed against studied 5/5, 4/5 and 4/5 strains, respectively. Furthermore, all of the tested combinations at 4xMIC were additive at 24 hours. No antagonism was observed. Conclusions The findings of this study suggest that a significant bactericidal effect was seen with all tested combinations. Our findings present significant implications for antibiotic choice for the treatment of infections caused by MDR A. baumannii.