Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible <i>Staphylococcus aureus</i> in a rabbit model of experimental endocarditis

Abstract Objectives To investigate if the addition of cloxacillin to vancomycin enhances activity both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods Vancomycin plus was compared with respective daptomycin. In vitro time–kill studies were performed using standard (105 cfu) high (108 inocula five MRSA, one glycopeptide-intermediate (GISA) strains. One (MSSA-678) (MRSA-277) strain selected be used vivo model. A human-like pharmacokinetics model applied equivalents 2 g/4 h IV daptomycin 6 mg/kg/day administered. optimize activity, dosage adjusted achieve an AUC/MIC ≥400. Results Daptomycin sterilized significantly more vegetations than (13/13, 100% versus 9/15, 60%; P = 0.02) showed a trend better (10/14, 71%; 0.09) against MSSA-678. Addition (13/15, 87%) effective (8/16, 50%; 0.05) similar (13/18, 72%; 0.6) MRSA-277. all treatment arms, bacterial isolates recovered from re-tested same susceptibility as original Conclusions proved synergistic bactericidal MRSA. most efficacious option settings prevalence, might good alternative empirical therapy S. aureus IE.