COMPARISON OF THE BACTERICIDAL ACTIVITIES OF PIPERACILLIN-TAZOBACTAM,TICARCILLIN-CLAVULANATE, AND AMPICILLIN-SULBACTAM AGAINST CLINICAL ISOLATES OF BACTEROIDES-FRAGILIS, ENTEROCOCCUS-FAECALIS, ESCHERICHIA-COLI, AND PSEUDOMONAS-AERUGINOSA

Owing to the broad spectrum of activity afforded by p-lactam-p-lactama se inhibitor preparations, these agents are frequently selected as emp iric therapy for the treatment of mixed infections such as intra-abdom inal and diabetic foot infections, either alone or in combination with an aminoglycoside. Twelve healthy volunteers were enrolled in a rando mized, open-label, four-way crossover trial comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and a mpicillin-sulbactam against microorganisms commonly isolated from mixe d infections, Subjects received the following regimens: (i) 3.375 g of piperacillin-tazobactam intravenously (i.v.) every 6 h (q6h), (ii) 4. 5 g of piperacillin-tazobactam i.v. q8h, (iii) 3.1 g of ticarcillin-cl avulanate i.v. q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. S erum bactericidal titers were determined and used to calculate the dur ation of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates each of Bacillus fr agilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas aerug inosa, The percentage of the dosing interval over which drug concentra tions in serum remained above the MIC for each organism was determined and compared with the observed duration of bactericidal activity. A s ignificant correlation between the predicted time above the MIC and th e duration of bactericidal activity,vas noted (r = 0.78; P < 0.001), A ll of the regimens demonstrated good activity against B. fragilis and E. coil. Against E. faecalis and P. aeruginosa, however, all of the re gimens provided bactericidal activity for less than 50% of the respect ive dosing intervals, These data suggest that use of shorter dosing in tervals or continuous-infusion regimens should be considered in combin ation with an aminoglycoside to improve the bactericidal profiles of t hese agents for E. faecalis and P. aeruginosa.