In vitro synergistic effect and mutant prevention concentration of eravacycline alone or in combination with various antibiotics against OXA-48 producing enterobacterales

This study examines the effects of combining eravacycline with various Antibiotics on carbapenem-resistant Enterobacterales (CRE) isolated from bloodstream infections. Fifty Enterobacterales isolates that produce the OXA-48 enzyme were tested for their Minimum Inhibitory Concentrations (MICs) using broth microdilution. The Mutant Prevention Concentrations (MPCs) of eravacycline, tigecycline, levofloxacin, colistin, fosfomycin, meropenem, and tobramycin were evaluated against CRE isolates. The bactericidal and synergistic effects of eravacycline, alone or in combination with Other Antibiotics, were assessed using time-kill curve (TKC) experiments. The in vitro synergistic activities of tested Antibiotics in combination with eravacycline were also determined by microbroth checkerboard technique, and results were interpreted using the fractional inhibitory concentration (FIC) index. The results of our study demonstrated that colistin exhibited the best bactericidal activity and the highest susceptibility rates among the evaluated strains. Eravacycline exhibited lower MPC values compared to tigecycline when used alone. The results of the TCK method showed that the most effective synergistic interactions were observed when eravacycline was combined with levofloxacin, colistin, or meropenem. The results obtained by microbroth checkerboard techniques also described synergistic activity with all tested eravacycline combinations against tested clinical isolates of Enterobacterales. No antagonism was detected. The study's results indicate that the combination of eravacycline with colistin, meropenem, tobramycin or levofloxacin showed synergistic activity against strains of Enterobacterales that produce OXA-48. This combination therapy may be a viable alternative for treating carbapenemase-producing Enterobacterales bacteria. In addition, eravacycline's lower MPC value suggests it may avoid the emergence of resistant mutant strains in the population.