title: Once versus thrice daily tobramycin alone and in combination with ceftazidime, ciprofloxacin and imipenem in an in vitro pharmacodynamic model.
abstract: The purpose of this study was to compare once daily (To24) and thrice daily (To8) tobramycin dosing regimens alone and in combination with ceftazidime, ciprofloxacin and imipenem against a clinical and ATCC strain of Pseudomonas aeruginosa. A one-compartment in vitro pharmacodynamic model was used to simulate bacteremic infection. Pharmacodynamic parameters, including rate of bacterial kill following the first dose or time to achieve a 99.9% reduction in bacterial counts (T99.9%), extent of bacterial kill with subsequent doses and bacterial count at 24 h were characterized for each regimen. Compared to To8 alone, the combination regimens had a shorter T99.9% (p = 0.045) and greater extent of bacterial kill following the first dose (p = 0.045). Compared to To24 alone, the combination regimens demonstrated similar rates (p = 0.067) and extents of bacterial kill following the first dose (p = 0.32), however, produced lower bacterial counts at 24 h (p = 0.045). The various combination regimens appeared equally effective considering rate and extent of bacterial kill following the first dose and residual inocula at 24 h. Ciprofloxacin-containing regimens demonstrated the most bacterial kill with subsequent doses, however, bacterial counts at 24 h were similar to those of other combination regimens.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada. s_zelenitsky@umanitoba.ca
authors.forename: S A
authors.initials: SA
authors.lastname: Zelenitsky
authors.forename: J A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: D J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: A
authors.initials: A
authors.lastname: Kabani
authors.forename: G G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001825:Body Fluid Compartments; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014031:Tobramycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D013845:Thienamycins; D002939:Ciprofloxacin; D015378:Imipenem; D002442:Ceftazidime; D014031:Tobramycin