title: Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA.
abstract: Eight heterogeneous vancomycin-intermediate S. aureus (h-VISA) and seven VISA clinical isolates confirmed by the population analysis profile/area under the curve ratio (PAP/AUC) were collected. We further performed the PAP/AUC, time-killing methods and MIC tests using vancomycin/teicoplanin alone or combination with susceptible breakpoint concentrations of cefazolin, cefmetazole, cefotaxime, and cefepime for these isolates. The PAP/AUC MIC curve shifted left after addition of cephalosporins with vancomycin or teicoplanin for both h-VISA and VISA isolates. With the combination of different cephalosporins with vancomycin or teicoplanin, the AUC/Mu3 AUC ratio decreased to <0.9 for the standard Mu3 isolate which are compatible with the definition of vancomycin susceptible S. aureus. These decreases ranged between 1.81-2.02 and 2.37-2.85-fold for h-VISA treated with cephalosporins and vancomycin or teicoplanin, and 2.05-4.59, and 2.93-4,89-fold for VISA treated with cephalosporins with vancomycin or teicoplanin. As measured by time-killing assays, the combinations of different cephalosporins with vancomycin concentrations at 1/2 and 1/4 MIC, exhibited a bactericidal and bacteriostatic effect in VISA. The mean fold of MIC decline for vancomycin base combinations ranged from 1.81-3.83 and 2.71-9.33 for h-VISA and VISA, respectively. Overall, this study demonstrated the enhanced antibacterial activity of vancomycin/teicoplanin after adding cephalosporins against clinical h-VISA/VISA isolates.
authors.affiliation: Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.|Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.|Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004357:Drug Synergism; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D017334:Teicoplanin / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D006020:Glycopeptides; D017334:Teicoplanin; D014640:Vancomycin