In vitro activities of ceftazidime/avibactam alone or in combination with antibiotics against multidrug-resistant Acinetobacter baumannii isolates

• Published in: Journal of global antimicrobial resistance. 2019-06, Vol.17, p.137-141
• Main Authors: Mataracı Kara, Emel, Yılmaz, Mesut, Özbek Çelik, Berna
• Format: Article
• Language: English
• Subjects: Ceftazidime/avibactam; Combination; Gram-negative; Synergy; β-Lactam inhibitors
• ISSN: 2213-7165; 2213-7173
• DOI: 10.1016/j.jgar.2018.12.004

•Forty clinical multidrug-resistant A.baumannii strains were screened and the MIC and MBC of tested antibiotics and the in-vitro synergistic activities of ceftazidime/avibactam with antibiotic combinations were determined.•The synergistic and bactericidal activities of ceftazidime/avibactam with colistin combinations were seen at 1 × MIC concentrations of all the studied strains.•The in-vitro synergistic activities of ceftazidime/avibactam+tobramycin and ceftazidime/avibactam+tigecycline combinations at 1 × MIC were observed against studied 4/5 strains, respectively.•The findings have very promising implications for antibiotic choice for the treatment of multidrug-resistant A. baumannii infections. Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (A. 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. Forty clinical MDR strains were screened, and minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (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 antibiotic combinations were determined by time-kill assays at 1× MIC and 4× MIC against five MDR A. baumannii isolates. Based on MIC results, all isolates of A. baumannii were resistant to ceftazidime/avibactam, except for AB-5. All isolates were found to be resistant to meropenem and levofloxacin. At 4× MIC, all of the tested antibiotics showed bactericidal effect (≥3log10killing). The synergistic activities of ceftazidime/avibactam+colistin, ceftazidime/avibactam+tobramycin and ceftazidime/avibactam+tigecycline combinations at 1× MIC were observed against studied 5/5, 4/5 and 4/5 strains, respectively. Furthermore, all of the tested combinations at 4× MIC were additive at 24h. No antagonism was observed. The findings of this study suggest that a significant bactericidal effect was seen with all tested combinations. T