Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads.
The in-vitro synergistic activity of YTR 830, a new beta-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 beta-lactamase inhibitors (8 mg/l) combined with doubling dilutions of beta-lactams in microdilution trays. Synergy was defined as a four-fold or greater decrease of beta-lactam MIC in the combination compared with the beta-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 clavulanate against Serratia, Citrobacter, Proteus and Providencia spp. Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8-16 mg/l, 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.
D000667:Ampicillin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000008:administration & dosage*; D004357:Drug Synergism; D004755:Enterobacteriaceae / Q000187:drug effects*; D008802:Mezlocillin / Q000008:administration & dosage; D009287:Naphthyridines; D010397:Penicillanic Acid / Q000008:administration & dosage*; D010406:Penicillins / Q000008:administration & dosage*; D010878:Piperacillin / Q000008:administration & dosage; D011549:Pseudomonas / Q000187:drug effects*; D013407:Sulbactam; D013982:Ticarcillin / Q000008:administration & dosage
D002969:Clavulanic Acids; D009287:Naphthyridines; D010406:Penicillins; D019818:Clavulanic Acid; C012122:apalcillin; D000667:Ampicillin; D010397:Penicillanic Acid; D013982:Ticarcillin; D008802:Mezlocillin; D013407:Sulbactam; D010878:Piperacillin