Synergistic effect of vancomycin combined with cefotaxime, imipenem, or meropenem against Staphylococcus aureus with reduced susceptibility to vancomycin

Background/aim: We investigated the synergistic effect between vancomycin and beta-lactams against vancomycin-susceptible (VSSA) and non-susceptible MRSA isolates [heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA]. Materials and methods: A total of 29 MRSA including 6 VISA, 14 hVISA and 9 VSSA isolates were subjected to a microbroth dilution-minimum inhibitory concentration (MIC) checkerboard using vancomycin combined with cefotaxime, imipenem or meropenem. To confirm synergistic activity, the representative strains of VISA, hVISA and VSSA were then selected for the time-kill curve method. Results: The combination of vancomycin with imipenem, meropenem and cefotaxime exhibited synergistic effects against 17 (2 VISA, 9 hVISA and 6 VSSA), 14 (3 VISA, 9 hVISA and 2 VSSA), and 5 (3 VISA and 2 hVISA) isolates respectively. Additive and indifferent effects were found in the remaining isolates but no antagonistic effect was observed. Using time-kill assay, the vancomycin combined with either imipenem or cefotaxime demonstrated synergism against both VISA and hVISA isolates, while the synergistic effect with meropenem was obtained in the VISA isolates only. Conclusion: This study demonstrated in vitro enhanced antibacterial activity of vancomycin plus beta-lactams against clinical hVISA or VISA isolates. These combinations may be an alternative treatment for MRSA infections in clinical practice.