Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus. Antimicrob. Agents Chemother

Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentra-tions of bactericidal agents were compared with treatment outcomes of experimental infective endocarditis due to a methicillin-susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin combinations, in vitro synergy testing using recommended fractions of the MIC failed to predict antagonism in vivo while concentrations above the MIC corresponded with antagonism in vivo. Standardized in vitro tests of susceptibility, such as determi-nation of the MIC, correlate well with the outcomes of methicillin-susceptible Staphylococcus aureus experimental en-docarditis treated with beta-lactam monotherapy (16). Fewer data about the correspondence of in vitro and in vivo results with combinations of antimicrobial agents are available, de-spite the fact that antimicrobial combinations are recom-mended to increase the bactericidal activity, to reduce the risk for emergence of resistance, or to shorten the duration of treatment of S. aureus endocarditis