In vitro activities of colistin, tigecycline and tobramycin, alone or in combination, against carbapenem-resistant enterobacteriaceae strains

Abstract

The aim of this study was to investigate the activities of various antibiotics, alone or in combination, against carbapenem-resistant Enterobacteriaceae (CRE). Minimum inhibitory concentrations (MICs) of meropenem, colistin, tigecycline and tobramycin were determined by microbroth dilution against 40 clinical strains. Carbapenemase-encoding genes were detected by PCR using specific primers. The in vitro synergistic activities of tigecycline, colistin and tobramycin in double antibiotic combinations were determined by the microbroth chequerboard technique, and results were interpreted using the fractional inhibitory concentration index (FICI). To confirm the results acquired by the chequerboard method, time-kill assays were performed on eight isolates representing four different susceptibility patterns. Based on MIC90 values, colistin was the most potent agent, followed by tigecycline and tobramycin. According to PCR studies, carbapenem resistance in tested Enterobacteriaceae isolates was most often mediated by OXA-48-type carbapenemases. With an FICI of <= 0.5 as the cut-off, synergistic interactions were most frequent with tigecycline + tobramycin (30%); other results for synergistic interactions were 23% for colistin + tobramycin and 9% for colistin + tigecycline. By time-kill assays, all tested antibiotic combinations demonstrated synergistic activity against at least three of the eight strains at 1x or 4x MIC. Overall, the combinations used in this study were effective regimens, demonstrating synergy or no interaction (indifference) against all tested strains. No antagonism was observed with either of the techniques. The findings of this study might play a useful role in selecting appropriate combinations when a single agent is inadequate against CRE strains.