In vitro comparison of N-formimidoyl thienamycin (MK0787) and Azlocillin with three aminoglycosides and ticarcillin against Pseudomonas aeruginosa

Abstract

The activities of N-formimidoyl thienamycin and azlocillin were compared with those of tobramycin, gentamicin, amikacin, and ticarcillin against 175 Pseudomonas aeruginosa isolates, including 24 strains with known mechanisms of resistance to aminoglycosides. The 50% mean inhibitory concentration for azlocillin was lower than for ticarcillin, but the 90% mean inhibitory concentration was similar for both drugs. All susceptible and multidrug-resistant strains were susceptible to N-formimidoyl thienamycin.Serious infections caused by Pseudomonas aeruginosa are associated with a high mortality rate, especially in patients with serious underlying disease, (1,2,6). N-Formimidoyl thienamycin (MK0787), a more stable P-lactam antibiotic than the parent compound, and azlocillin, a new ureido penicillin, have been shown to possess potent activity against many microbial strains, including P. aeruginosa (3-5, 7-13, 15, 17, 18 ml) and for azlocillin were 16 and 128 ,ug/ml (GmMIC 26 ,ug/ml), respectively. The activity of N-formimidoyl thienamycin and azlocillin was compared with reference antibiotics against 151 isolates of P. aeruginosa. The MIC50, MIC90, range, and GmMIC in micrograms per milliliter were as follows: N-formimidoyl thienamycin, 2, 4, 0.5 to 32, and 2.5; azlocillin, 16, 128, 4 to 1,024, and 26.5; tobramycin, 1, 4, 0.125 to >64, and 1.7; gentamicin, 4, 16, 0.125 to >512, and 517; amikacin, 8, 32, 0.5 to 64, and 7.7; and ticarcillin, 32, 128, 8 to >1,024, and 39.8. Table 1 shows the activity of N-formimidoyl thienamycin against strains resistant to one or more reference antibiotics. We found that 4 ,ug/ml of N-formimidoyl thienamycin inhibited >86% of the P. aeruginosa strains tested and that 32 ,ug/ ml inhibited all of the P. aeruginosa strains tested. The activity of N-formimidoyl thienamycin against seven strains intermediate or highly resistant to azlocillin and reference antibiotics showed that five strains were inhibited by <4 ,ug/ml and all strains were inhibited by 32 ,ug of N-formimidoyl thienamycin per ml. For 24 strains of P. aeruginosa with known mechanisms of resistance for amikacin, tobramycin, or both, all but one strain was inhibited by <8 ,ug/ ml of N-formimidoyl thienamycin (Table 2). Of these 24 strains resistant to azlocillin (MIC 364 ,ug/ml) 14 were susceptible to z 8 ,ug/ml of Nformimidoyl thienamycin.Our data compare closely with published studies which included smaller numbers of P. aeruginosa strains (4,8,9,11,12,15