Evaluation of the synergy of ceftazidime/avibactam in combination with colistin, doripenem, levofloxacin, tigecycline, and tobramycin against OXA-48 producing enterobacterales

Abstract

This study aims to analyze the effect of ceftazidime/avibactam plus various antibiotics against OXA-48-producing Enterobacterales isolated from Intensive Care Units. Seventy-four non-duplicate OXA-48-producing Enterobacterales isolates were screened for their MICs by the microbroth dilution method. The in-vitro bactericidal and synergistic activities of ceftazidime/avibactam alone or in combination with other antibiotics were determined by time-kill curve assays. According to our results, colistin was the most active drug with higher susceptibility rates in the strains. Colistin, levofloxacin, tobramycin, and doripenem showed bactericidal effects against different isolates. The best synergistic interactions were achieved with ceftazidime/avibactam + colistin, ceftazidime/avibactam + tobramycin, and ceftazidime/avibactam + tigecycline against studied strains used at 1xMIC concentrations at 24 h. No antagonism was observed against studied OXA-48-producing Enterobacterales strains. The findings of this study suggest that ceftazidime/avibactam plus colistin, tobramycin, or tigecycline were more effective against OXA-48-producing Enterobacterales strains. This combination therapy could be an alternative antibiotic therapy for carbapenemase-producing Enterobacterales strains.