Comparison of fixed concentration and fixed ratio options for testing susceptibility of gram-negative bacilli to piperacillin and piperacillin/tazobactam.
Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.
Pfaller
M A
MA
Department of Pathology, Oregon Health Sciences University, Portland 97201.
Barry
A L
AL
Fuchs
P C
PC
Gerlach
E H
EH
Hardy
D J
DJ
McLaughlin
J C
JC
D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000494:pharmacology; D010878:Piperacillin / Q000008:administration & dosage / Q000494:pharmacology*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin