Escherichia coli, and Pseudomonas aeruginosa

Owing to the broad spectrum of activity afforded by b-lactam–b-lactamase inhibitor preparations, these agents are frequently selected as empiric therapy for the treatment of mixed infections such as intra-abdominal and diabetic foot infections, either alone or in combination with an aminoglycoside. Twelve healthy volunteers were enrolled in a randomized, open-label, four-way crossover trial comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against microorganisms commonly isolated from mixed 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-clavulanate i.v. q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. Serum bactericidal titers were determined and used to calculate the duration of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates each of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudo-monas aeruginosa. The percentage of the dosing interval over which drug concentrations in serum remained above the MIC for each organism was determined and compared with the observed duration of bactericidal activity. A significant correlation between the predicted time above the MIC and the duration of bactericidal activity was noted (r 5 0.78; P < 0.001). All of the regimens demonstrated good activity against B. fragilis an