title: Comparative evaluation of the in vitro activity of three combinations of beta-lactams with beta-lactamase inhibitors: piperacillin/tazobactam, ticarcillin/clavulanic acid and ampicillin/sulbactam.
abstract: Recently, two new combinations of Beta-lactam antibiotics with Beta-lactamase inhibitors became commercially available in Brazil: piperacillin/tazobactam and ampicillin/sulbactam. This study was designed to assess and compare the in-vitro activity of these new compounds, as well as that of ticarcillin/clavulanic acid, against bacteria isolated in our environment. A total of 749 bacteria isolated at São Paulo Hospital were tested using the disk diffusion method, in compliance with NCCLS standardization, using strict quality control. Only one sample per patient was included in the study. Oxacillin-resistant staphylococcus samples were not included in this study. Of the total samples tested, 84.5% were susceptible to piperacillin/tazobactam, 81.2% to ticarcillin/clavulanic acid, and 77.6% to ampicillin/sulbactam. Piperacillin/tazobactam was also found to be the most active combination of the three against Enterobacteriaceae ( n = 312), inhibiting 91.7% of the bacteria tested. Ticarcillin/clavulanic acid was active against 85.8% of the Enterobacteriaceae, while ampicillin/sulbactam inhibited 83.2% of the samples. This order of the spectrum of action (piperacillin/tazobactam > ticarcillin/clavulanic acid >ampicillin/sulbactam )was maintained for the majority of Enterobacteriaceae species analyzed. Pseudomonas aeruginosa ( n = 117) showed extremely high resistance to the three combinations. Piperacillin/tazobactam was active against 61.5% of the samples, while ticarcillin/clavulanic acid was active against 56.4% of the samples of this species. The activity of ampicillin/sulbactam against P. aeruginosa was extremely low; however, this was the most active combination against Acinetobacter baumannii ( 87.0% susceptibility). Piperacillin/tazobactam was the most active combination against Stenotrophomonas (Xanthomonas )maltophilia (100% susceptibility) and Burkholderia cepacia (90.9% susceptibility). The three combinations showed excellent activity against the Gram-positive cocci tested (97.3% to 98.2% susceptibility). In sum, piperacillin/tazobactam was more active against all Gram-negative species than the other two combinations, with the exception of A. baumannii, and showed similar activity against Gram-positive cocci.
authors.affiliation: Special Clinical Microbiology Laboratory, Department of Infectious and Parasitic Diseases, Universidade Federal de São Paulo, Brazil. heliosader@originet.com.br
authors.forename: H S
authors.initials: HS
authors.lastname: Sader
authors.forename: I
authors.initials: I
authors.lastname: Tosin
authors.forename: L
authors.initials: L
authors.lastname: Sejas
authors.forename: E
authors.initials: E
authors.lastname: Miranda
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology; D003428:Cross Infection / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D013407:Sulbactam / Q000494:pharmacology; D000078142:Tazobactam; D013982:Ticarcillin / Q000494:pharmacology; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000667:Ampicillin; D010397:Penicillanic Acid; D013982:Ticarcillin; D013407:Sulbactam; D000078142:Tazobactam; D010878:Piperacillin