Comparative antimicrobial activity of FK037, cefpirome, ceftazidime and cefepime against aminoglycoside-sensitive and aminoglycoside-resistant Pseudomonas aeruginosa and Pseudomonas spp.

The activities of FK037, cefpirome, ceftazidime and cefepime against 71 aminoglycoside-resistant, 35 aminoglycoside-sensitive, 29 cystic fibrosis Pseudomonas aeruginosa isolates, and 31 Pseudomonas spp. strains were studied using the agar dilution technique (final inoculum 10(4) c.f.u./spot). The MIC90 for aminoglycoside-sensitive P. aeruginosa against FK037, cefpirome, ceftazidime and cefepime was 32, 16, 8 and 16 mg/l, respectively. The MIC90 for P. aeruginosa strains resistant to one or more aminoglycosides was similar for FK037, cefpirome and ceftazidime (128 mg/l) and two dilutions lower for cefepime (32 mg/l). The MIC90 for P. aeruginosa isolates highly resistant to all three aminoglycosides (MIC > or = 128 mg/l) was 64 mg/l for FK037 and cefpirome, and 32 mg/l for ceftazidime and cefepime. The MIC90 for P. aeruginosa from patients with cystic fibrosis was 32 mg/l for all four cephalosporins tested, and 8, 32 and 64 for tobramycin, gentamicin and amikacin, respectively. Xanthomonas maltophilia was resistant to all four cephalosporins and three aminoglycosides. The activity of ceftazidime and cefepime was one to two dilutions greater against P. cepacia and P. picketti than of FK037 and cefpirome. The activity of ceftazidime was two dilutions greater than the other three cephalosporins against P. fluorescens. In kinetic time kill curves against P. aeruginosa, all four cephalosporins demonstrated similar activity at 6 and 24 h when tested at 1 x MIC. At 2 x MIC, regrowth was less at 24 h for cefepime, cefpirome and FK037 than for ceftazidime. In time kill curves for P. aeruginosa, synergy was clearly demonstrated at 1/4 MIC and 1/2 MIC concentrations for FK037 and tobramycin.