Activity of amikacin, ertapenem, ciprofloxacin and levofloxacin alone and in combination against resistant nosocomial pathogens by time-kill

Objective: The purpose of this study was to determine the synergistic activity of amikacin/ertapenem, fluoroquinolones (ciprofloxacin and levofloxacin)lertapenem and amikacinffluoroquinolones combinations against resistant nosocomial pathogens. Methods: Time-kill studies wereperformed over 24 hours using an inoculum of5 x 106-1 X 107 cJu/mL. Antibiotics were tested at the 1 x MIC and 4 x MIC concentrations. Results: At MIC andlor 4 x MIC concentrations, the antibiotic combinations showed additive or synergistic activity against Acinetobacter strains and extended spectrum beta-lactamase producing Klebsiella pneumoniae. In Escherichia coli strains, synergy was seen when amikacin was combined with ertapenem, ciprofloxacin and levofloxacin; ertapenem in combination with fluoroquinolones demonstrated antagonism. In Pseudomonas aeruginosa strains, synergistic effect was exhibited by ertapenem plus amikacin and ertapenem plus fluoroquinolones. The antibiotic combinations showed antagonistic interaction in methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Conclusion: The antibiotic combinations showed additive or synergistic activity against many gramnegative pathogens.