Antibacterial activity of apalcillin (PC-904) against gram-negative bacilli, especially ampicillin-, carbenicillin-, and gentamicin-resistant clinical isolates

Apalcillin (PC-904) is active against carbenicillin- and ampicillin-resistant strains of gram-negative bacilli. Among Pseudomonas aeruginosa strains highly resistant to carbenicillin (>/=3,200 mug/ml), half of them were susceptible to PC-904 at a concentration of 50 to 1,600 mug/ml. The minimal inhibitory concentration of PC-904 against P. aeruginosa strains resistant to carbenicillin (400 to 1,600 mug/ml) ranged from 3.1 to 25 mug/ml. Ampicillin- and carbenicillin-resistant Enterobacteriaceae strains were similarly susceptible to PC-904. However, drug resistance to PC-904 was already apparent among some strains of P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, and P. morganii, recently isolated in Japan; i.e., 4, 35, 32, 4, 6, and 14% of strains isolated were resistant. PC-904 was more active, on the Other hand, than ampicillin and carbenicillin against antibiotic-susceptible Enterobacteriaceae and also showed high activity against most species of Pseudomonadaceae, especially P. cepacia and P. aeruginosa. The minimum inhibitory concentrations of PC-904 were greatly affected by inoculum size when the organisms tested were strains producing large amounts of Beta-lactamase.