Journal of Antimicrobial Chemotherapy (1986) 18, 177-184
© 1986 The British Society for Antimicrobial Chemotherapy
research-article |
Comparative activities of the ß-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads
*Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
Pediatrics Case Western Reserve University School of Medicine Cleveland, Ohio
Division of Chemotherapy, Kobe College Research Institute Nishinomiya, Japan
accepted 31 January 1986
The in-vitro synergistic activity of YTR 830, a new ß-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam. Synergy testing was performed with fixed concentrations of ß-lactamase inhibitors (8 mg/1) combined with doubling dilutions of Blactams in microdilution trays. Synergy was defined as a four-fold or greater decrease of ß-lactam MIC in the combination compared with the ß-lactam alone. For 79 ticarcillin-resistant Enterobacteriaceae, ticarcillin-YTR 830 and ticarcillin-clavulanate were synergistic against 90% of strains; for ticarcillin-sulbactam, 70% showed synergy. The synergistic activity of all three inhibitors was similar against strains resistant only to ticarcillin, for strains resistant to all four extended-spectrum penicillins, the activity of ticarcillin with YTR 830 and clavulanate was similar (synergy against 79% of strains) and superior to ticarcillin-sulbactam (synergy against 39% of strains). YTR 830 was more active than claulanate against Serratia, Citrobacter, Proteus and Providencia spp. Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8–16 mg/1, showed synergy with inhibitors against 37–87% of strains. Amongst pseudomonads, no synergy was demonstrated against Pseudomonas aeruginosa; ticarcillin produced synergy with the inhibitors against Ps. maltophilia, while piperacillin-YTR 830 and apalcillin-YTR 830 were synergistic against Ps. cepacia. YTR 830 appears to have comparable in-vitro activity to that of clavulanate, and further development of this compound is warranted.
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