Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance.

PURPOSE

To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains.

METHODS

In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 10 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination.

RESULTS

The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively.

CONCLUSIONS

The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance.