title: Effect of antibiotic sequence on combination regimens against Pseudomonas aeruginosa in a multiple-dose, in vitro infection model.
abstract: The goal of this study was to investigate the effect of antibiotic sequence on combination regimens against Pseudomonas aeruginosa in an in vitro infection model. Ceftazidime plus ciprofloxacin and ceftazidime plus tobramycin were dosed every 12 h for 48 h using simultaneous or staggered administration. Simultaneous dosing and ceftazidime followed by ciprofloxacin or tobramycin were significantly more active at both 24 h (p = 0.03) and 48 h (p < 0.0001) than ciprofloxacin or tobramycin followed by ceftazidime. Final bacterial kill was sixfold greater with the former regimens. This study showed that antibiotic sequence had a significant and class dependent effect on antibacterial response. The clinical relevance of these observations warrants further investigations in animal models.
authors.affiliation: Faculty of Pharmacy, University of Manitobas, Winnipeg, Manitoba, Canada. zelenits@ms.umanitoba.com
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Zelenitsky
authors.forename: Harris
authors.initials: H
authors.lastname: Iacovides
authors.forename: Godfrey K M
authors.initials: GK
authors.lastname: Harding
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ariano
mesh_terms: D002442:Ceftazidime / Q000493:pharmacokinetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D014031:Tobramycin / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D002939:Ciprofloxacin; D002442:Ceftazidime; D014031:Tobramycin