Beta-Lactams combinations with Vancomycin provide synergy against VSSA, hVISA, and VISA [PublishAheadOfPrint]

Background: Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant S. aureus (MRSA) infections has lead to the emergence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA). In vitro data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin susceptible Staphylococcus aureus (VSSA), hVISA, and VISA.

Methods: Fifty randomly selected clinical MRSA strains with varying susceptibility to vancomycin were evaluated for vancomycin alone and vancomycin in combination with varying concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF) minimum inhibitory concentration (MIC). The potential for synergy was assessed by 24h time-kills.

Results: Beta-lactams reduced vancomycin MIC values against all strains (4-16 fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated a similar extent of killing at 24h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (P < 0.001 for all comparisons). All single agent exposures demonstrated no activity at 24h.

Conclusions: The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA compared to any agent alone, supporting the potential use of vancomycin/beta-lactams combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these Staphylococcus strains.

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