Bactericidal activities of antibiotics against vancomycin-resistant Enterococcus faecium blood isolates and synergistic activities of combinations

Abstract

The effects of teicoplanin (8 μg/ml), ampicillin (64 μg/ml), imipenem (32 μg/ml), and gentamicin (4 μg/ml), alone and in combination, against 13 unique blood isolates of vancomycin-resistant (MIC for 90% of isolates tested [MIC90], 512 μg/ml), teicoplanin-susceptible (MIC90, 2.0 μg/ml), ampicillin-resistant (MIC90, 128 μg/ml), and non-β-lactamase-producing Enterococcus faecium (vancomycin-resistant enterococci [VRE] isolates) were evaluated by time-kill studies. All 13 isolates exhibited high-level resistance to streptomycin; 7 isolates exhibited high-level gentamicin resistance (HLGR). After 24 h of incubation, ampicillin (64 μg/ml) combined with gentamicin (4 μg/ml) was bactericidal against three of the VRE isolates that did not display HLGR. Synergy between ampicillin and gentamicin was not observed against these isolates. Teicoplanin (8 μg/ml) alone was bactericidal at 24 h against five of six VRE isolates that lacked HLGR, but was not bactericidal against any HLGR VRE isolate at that time point. The addition of ampicillin (64 μg/ml) or imipenem (32 μg/ml) to teicoplanin did not significantly enhance the killing of HLGR VRE isolates as a group (P = 0.335). However, there was a trend toward improved killing of some HLGR VRE isolates by teicoplanin plus imipenem. Vancomycin (32 μg/ml) combined with ampicillin (64 μg/ml) was neither bactericidal nor synergistic against HLGR VRE isolates. Overall, bactericidal activity was attainable against 7 of 13 VRE isolates at 24 h.