The combinations of cefazolin with linezolid and cefazolin with clindamycin are indifferent against methicillin-susceptible Staphylococcus aureus.

Antimicrobial combinations resulting in synergy against Staphylococcus aureus are desirable for improving clinical efficacy in the treatment of severe infections caused by this pathogen. Despite an existing biological rationale for the combination of cefazolin and linezolid for methicillin-susceptible S. aureus (MSSA), this combination has yet to be evaluated for in vitro synergy. We employed the checkerboard and E-test methods of synergy assessment to evaluate cefazolin in combination with linezolid against 19 clinical MSSA isolates from two centers and compared the findings to cefazolin in combination with another protein synthesis inhibitor, clindamycin. Synergy was determined using the fractional inhibitory concentration index (FICI) through both the checkerboard and combined E-test assays. Combinations of cefazolin with linezolid and clindamycin demonstrated indifference through both methods (median checkerboard FICI of 1.11 and 1.25 and median E-test FICI of 0.99 and 0.88, respectively). Although the studied combinations were not synergistic, results of both assays were categorically consistent and suggest that the E-test is a robust method for evaluating synergy in S. aureus isolates.IMPORTANCEThe combinations of cefazolin and linezolid and cefazolin with clindamycin are potentially clinically relevant combinations for the treatment of severe S. aureus infections. However, the synergistic effects of these combinations against clinical MSSA isolates have not been previously determined. We performed checkerboard and E-test synergy testing and demonstrated that these combinations were indifferent for MSSA isolates. Although synergy was not identified for these combinations, the methods of synergy assessment agreed, highlighting the potential benefit for the combined gradient diffusion assay in future synergy assessment. Due to ease of use and categorical agreement with the checkerboard method in this study, this method may be beneficial for further implementation in synergy testing, leading to the identification of synergistic combinations that may improve treatment success for severe S. aureus infections.