The most efficacious antimicrobial therapy to aid in the successful elimination of\nresistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of\nS. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in\ncombination with cefazolin (CFZ). The objective of this study was to observe whether there was a\ntherapeutic improvement in adding a beta-lactam to a glycopeptide, lipopeptide, or a lipoglycopeptide.\nWe completed a series of in vitro tests including minimum inhibitory concentration testing (MIC) of\nthe antimicrobials in combination, time-kill analysis (TKA), and a 168 h (7-day) one-compartment\npharmacokinetic/pharmacodynamic (PK/PD) model on two daptomycin non-susceptible (DNS),\nvancomycin intermediate S. aureus strains (VISA), D712 and 6913. Results from our MIC testing\ndemonstrated a minimum 2-fold and a maximum 32-fold reduction in MIC values for DAL, VAN,\nand DAP in combination with CFZ, in contrast to either agent used alone. The TKAs completed\non four strains paralleled the enhanced activity demonstrated via the combination MICs. In the\none-compartment PK/PD models, the combination of DAP plus CFZ or VAN plus CFZ resulted in a\nsignificant (p < 0.001) improvement in bactericidal activity and overall reduction in CFU/ml over the\n7-day period. While the addition of CFZ to DAL improved time to bactericidal activity, DAL alone\ndemonstrated equal and more sustained overall activity compared to all other treatments. The use of\nDAL alone, with or without CFZ and the combinations of VAN or DAP with CFZ appear to result in\nincreased bactericidal activity against various recalcitrant S. aureus phenotypes.
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