Discrepancies between disk diffusion and broth susceptibility studies of the activity of ticarcillin plus clavulanic acid against ticarcillin-resistant Pseudomonas aeruginosa.
Ticarcillin and clavulanic acid in combination were tested against 40 Pseudomonas aeruginosa isolates resistant to ticarcillin by disk diffusion. A total of 21 isolates (53%) were susceptible to ticarcillin-clavulanate by disk diffusion, under currently recommended criteria for ticarcillin susceptibility. Macro-broth dilution tests (ticarcillin plus clavulanic acid, 2 micrograms/ml) confirmed susceptibility (MIC less than or equal to 64 micrograms/ml) of only 8 (38%) of 21 isolates. Time-kill studies of disk diffusion susceptible isolates indicated 2 log10 or greater killing of most isolates at 6 h in broth containing ticarcillin (64 micrograms/ml) combined with clavulanic acid (1, 2, 5, or 10 micrograms/ml). After 6 h, regrowth was common in all concentrations of clavulanic acid except 10 micrograms/ml. Regrowth populations were resistant to ticarcillin-clavulanate by MIC determination. Poor bactericidal activity of ticarcillin-clavulanate against ticarcillin-resistant P. aeruginosa was confirmed, as most isolates did not undergo 99.9% or greater killing at 24 h in all concentrations of clavulanic acid. Serotype O-11 was our most common serotype and was associated with disk diffusion "pseudosusceptibility." Concomitant disk diffusion testing of ticarcillin-clavulanate and ticarcillin is recommended for testing the susceptibility of P. aeruginosa to ticarcillin-clavulanate by disk diffusion. P. aeruginosa isolates resistant to ticarcillin should as a rule be considered also resistant to ticarcillin-clavulanate, despite apparent susceptibility by disk diffusion.
D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D004058:Diffusion; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013982:Ticarcillin / Q000494:pharmacology*
D002969:Clavulanic Acids; D010406:Penicillins; D019818:Clavulanic Acid; D013982:Ticarcillin