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 c eftazidime, ciprofloxacin and imipenem against a clinical and ATCC str ain of Pseudomonas aeruginosa. A one-compartment in vitro pharmacodyna mic model was used to simulate bacteremic infection. Pharmacodynamic p arameters, including rate of bacterial kill following the first dose o r time to achieve a 99.9% reduction in bacterial counts (T-99.9%)), ex tent of bacterial kill with subsequent doses and bacterial count at 24 h were characterized for each regimen. Compared to To8 alone, the com bination regimens had a shorter T-99.9% (p = 0.045) and greater extent of bacterial kill following the first dose (p = 0.045). Compared to T o24 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 va rious combination regimens appeared equally effective considering rate and extent of bacterial kill following the first dose and residual in ocula 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.