Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus.
Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentrations 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.
Brandt
C M
CM
Infectious Diseases Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905.
Rouse
M S
MS
Tallan
B M
BM
Wilson
W R
WR
Steckelberg
J M
JM
D000818:Animals; D002437:Cefazolin / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005839:Gentamicins / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009254:Nafcillin / Q000494:pharmacology; D011237:Predictive Value of Tests; D011817:Rabbits; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus / Q000187:drug effects*; D013997:Time Factors; D000097572:Cefpirome
D002437:Cefazolin; D002511:Cephalosporins; D005839:Gentamicins; D009254:Nafcillin; D012293:Rifampin; D000097572:Cefpirome