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. AmongPseudomonas aeruginosa strains highly resistant to carbenicillin (≥3,200 μg/ml), half of them were susceptible to PC-904 at a concentration of 50 to 1,600 μg/ml. The minimal inhibitory concentration of PC-904 againstP. aeruginosa strains resistant to carbenicillin (400 to 1,600 μg/ml) ranged from 3.1 to 25 μg/ml. Ampicillin- and carbenicillin-resistantEnterobacteriaceae strains were similarly susceptible to PC-904. However, drug resistance to PC-904 was already apparent among some strains ofP. aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris , andP. 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-susceptibleEnterobacteriaceae and also showed high activity against most species ofPseudomonadaceae , especiallyP. cepacia andP. 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.