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Novel Combination of Vancomycin (VAN) and Cefazolin (CFZ) Or Ertapenem (ERT): a Synergistic Combination for Complicated Staphylococcus Aureus Bacteraemia

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Novel Combination of Vancomycin (VAN) and Cefazolin (CFZ) Or Ertapenem (ERT): a Synergistic Combination for Complicated Staphylococcus Aureus Bacteraemia Session: P101 What is hot in Staphylococcus aureus bloodstream infection ? Category: 2b. Severe sepsis, bacteraemia & endocarditis 25 April 2017, 12:30 - 13:30 P2129 Novel combination of vancomycin (VAN) and cefazolin (CFZ) or ertapenem (ERT): a synergistic combination for complicated Staphylococcus aureus bacteraemia Meenal Malviya*1, Michael Rybak2, Nivedita Singh3, Nikki Tran4 1Wayne State University/Dmc; Infectious Disease 2Anti-Infective Research Laboratory; College of Pharmacy & Health Sciences Wayne State University 3Anti-Infective Research Laboratory; College of Pharmacy & Health Sciences Wayne State University 4College of Pharmacy & Health Sciences Wayne State University; Anti-Infective Research Laboratory, College of Pharmacy & Health Sciences Wayne State University Background: Vancomycin (VAN) treatment failure of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections has been well described. While In vitro data suggest potent synergy between several beta-lactams (BLs), the combination of VAN and CFZ or ERT has not been well studied. Our objective was to evaluate the potential for synergy with CFZ or ERT with VAN against several different antibiotic resistant phenotypes. Material/methods: VAN, ERT and CFZ MIC testing was performed on 15 randomly selected MRSA strains from the Anti-Infective Research Laboratory library by broth microdilution in duplicate. There were 9 strains of VAN susceptible MRSA, 2 Linezolid resistant (LNZ-R), 2 heteroresistant VISA (hVISA), 2 VAN intermediate susceptible aureus (VISA). VAN MIC values were evaluated in the presence of 0.5 x MIC of CFZ and ERT for all MRSA. The potential for synergy was also evaluated using 24-hour time- kill curve (TKC ) against 10 randomly selected strain from each MRSA phenotype. In TKC experiments, VAN at 0.5 x MIC was used in combination with CFZ and ERT at 0.5 x MIC. Synergy was defined as >2 log10 CFU/ml difference between combination and the most active single agent at 24 hours. Results: MIC values for VAN susceptible MRSA ranged from 0.5 – 2 µg/ml, 8 µg/ml for the 2 VISA strains, 2 µg/ml for hVISA, and 0.5 µg/ml for LNZ-R strains. Ertapenem MIC values for most organism were resistant (MIC>32). In combination MIC studies, VAN MIC decreased (0.5-2) in presence of CFZ and also decreased ( 0.3-2) in presence of ERT among all the MRSA. In TKCs, VAN + CFZ was synergistic against all phenotypes although for VISA strains it was less synergistic. VAN + ERT also showed synergy for most MRSA strains but not less for VISA strains. Overall, they were still synergistic. All single agent exposures demonstrated no activity at 24 hours. The bacterial kill with VAN +CFZ and ERT was significantly greater than VAN alone (p< 0.001). Conclusions: Our data further strengthens previous studies on synergistic combination of VAN with CFZ and for VAN with ERT combination therapy which has not been previously reported. These combinations may be of clinical use especially in cases with persistent bacteremia or complicated MRSA infections. .
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