Once versus thrice daily tobramycin alone and in combination with ceftazidime, ciprofloxacin and imipenem in an in vitro pharmacodynamic model.
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.
Zelenitsky
S A
SA
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada. s_zelenitsky@umanitoba.ca
Karlowsky
J A
JA
Hoban
D J
DJ
Kabani
A
A
Zhanel
G G
GG
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*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D013845:Thienamycins; D002939:Ciprofloxacin; D015378:Imipenem; D002442:Ceftazidime; D014031:Tobramycin