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PC-904, sodium 6-{d(-)-alpha-(4-hydroxy-1,5-naphthyridine-3-carboxamido) phenylacetamido}-penicillanate, is a novel semisynthetic penicillin derivative that possesses a broad spectrum of in vitro and in vivo antibacterial activities. In low concentrations, PC-904 inhibits growth against large proportions of the gram-positive and gram-negative organisms susceptible to carbenicillin and gentamicin. In addition, PC-904 is several times more potent than carbenicillin against organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Shigella, Salmonella, Neisseria gonorrhoeae, and Bacteroides fragilis. Most striking are the inhibitory effects of PC-904 against P. aeruginosa and K. pneumoniae. Against these two clinical isolates, PC-904 is, respectively, 35 and 100 times more active than carbenicillin. The minimum inhibitory concentrations of PC-904 against P. aeruginosa are comparable to those of gentamicin. PC-904 acts bactericidally. The effect of inoculum size on the antibacterial activity is often small and generally comparable to carbenicillin. The rate of binding to serum protein is high (88 to 98%), but the effect of the addition of serum on the drug's activity is not marked, because such binding is reversible. It is confirmed that PC-904 has a very potent in vivo antibacterial activity against gram-negative and gram-positive organisms. Against systemic infections with P. aeruginosa, K. pneumoniae, and E. coli in mice, PC-904 is 7 to 10 times, over 8 times, and 2 to 15 times more active than carbenicillin, respectively.

PC-904, a Novel Broad-Spectrum Semisynthetic Penicillin with Marked Antipseudomonal Activity: Microbiological Evaluation