Impact of cefazolin co-administration with vancomycin to reduce development of vancomycin-intermediate Staphylococcus aureus

VAN MIC of both organisms increased from 1 to 4 mg/L within 144 h under subtherapeutic VAN exposure. Increase in VAN MIC was associated with increased glyco/lipopeptides MICs. Additionally, increased survival in LL-37 killing assays from 40% to >90% accompanied the increase in VAN MIC. Addition of CFZ prevented the emergence of VAN-intermediate S. aureus. PAPs demonstrated an attenuation of VAN area under the curve shift (reduced organism selection with higher MICs values) when suboptimal VAN exposure was accompanied with CFZ compared to VAN alone (MSSA 17.81 versus 36.027, MRSA −0.35 versus 17.92, respectively). Given the emerging data on the clinical benefits of β-lactam adjunctive therapy in refractory MRSA bacteremia, additional studies on a larger collection of clinical isolates are needed to establish the utility of VAN plus CFZ for treatment of MRSA bacteremia.