Effects of azlocillin in combination with clavulanic acid, sulbactam, and N-formimidoyl thienamycin against beta-lactamase-producing, carbenicillin-resistant Pseudomonas aeruginosa

Abstract

We investigated the effects of the combination of azlocillin with the beta-lactamase inhibitors clavulanic acid and sulbactam and with N-formimidoyl thienamycin against strains of Pseudomonas aeruginosa with R-factor-mediated carbenicillin resistance. The 10 strains tested (1 R-, 9 R+) were isogenic, except for the presence of individual plasmids determining each of nine plasmid-mediated beta-lactamases found in P. aeruginosa. We utilized a checkerboard technique for testing antibiotic combinations. Low concentrations of clavulanic acid produced synergy with azlocillin against the strains producing the TEM-1, TEM-2, PSE-1, PSE-3, and PSE-4 beta-lactamases; for the strains producing the OXA-1, OXA-2, OXA-3, and PSE-2 beta-lactamases, such synergy was not found. With sulbactam, synergy was demonstrated in all strains except that producing PSE-2 beta-lactamase; for several strains, however, the concentration of sulbactam required to produce synergy was substantially higher than that for clavulanic acid. N-Formimidoyl thienamycin was highly active as a single agent against all of the strains, regardless of beta-lactamase production. The combination of N-formimidoyl thienamycin and azlocillin produced synergy against only two of the strains tested.