title: Failure of time-kill synergy studies using subinhibitory antimicrobial concentrations to predict in vivo antagonism of cephalosporin-rifampin combinations against Staphylococcus aureus.
abstract: 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.
authors: Infectious Diseases Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905.
authors: C M
authors: CM
authors: Brandt
authors: M S
authors: MS
authors: Rouse
authors: B M
authors: BM
authors: Tallan
authors: W R
authors: WR
authors: Wilson
authors: J M
authors: JM
authors: Steckelberg
mesh_terms: 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
chemical_list: D002437:Cefazolin; D002511:Cephalosporins; D005839:Gentamicins; D009254:Nafcillin; D012293:Rifampin; D000097572:Cefpirome