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 beta-lactam-beta-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 regimes: (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 of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas 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 was noted (r = 0.78; P < 0.001). All of the regimens demonstrated good activity against B. fragilis and E. coli. Against E. faecalis and P. aeruginosa, however, all of the regimens provided bactericidal activity for less than 50% of the respective dosing intervals. These data suggest that use of shorter dosing intervals or continuous-infusion regimens should be considered in combination with an aminoglycoside to improve the bactericidal profiles of these agents for E. faecalis and P. aeruginosa.
Klepser
M E
ME
Department of Pharmacy, Hartford Hospital, Connecticut 06102, USA. michael-klepser@uiowa.edu
Marangos
M N
MN
Zhu
Z
Z
Nicolau
D P
DP
Quintiliani
R
R
Nightingale
C H
CH
D000328:Adult; D000667:Ampicillin / Q000493:pharmacokinetics / Q000494:pharmacology; D001441:Bacteroides fragilis / Q000187:drug effects* / Q000302:isolation & purification; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000302:isolation & purification; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D010878:Piperacillin / Q000493:pharmacokinetics / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D015610:Serum Bactericidal Test; D013407:Sulbactam / Q000493:pharmacokinetics / Q000494:pharmacology; D000078142:Tazobactam; D013982:Ticarcillin / Q000493:pharmacokinetics / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; C035444:sultamicillin; D000667:Ampicillin; D010397:Penicillanic Acid; D013982:Ticarcillin; D013407:Sulbactam; D000078142:Tazobactam; D010878:Piperacillin