Moxalactam (6059-S), a novel 1-oxa-beta-lactam with an expanded antibacterial spectrum: laboratory evaluation

Abstract

Moxalactam (6059-S) {7beta-[2-carboxy-2-(4-hydroxyphenyl)acetamido]-7alpha-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]-methyl]-1-oxa-1-dethia-3-cephem-4- carboxylic acid disodium salt} is a new semisynthetic 1-oxa-beta-lactam derivative for parenteral use. It was highly active against a broad range of gram-negative microorganisms, including those resistant to other cephalosporins. Moreover, it had widely expanded antibacterial spectra which included Haemophilus influenzae, indole-positive Proteus, Enterobacter, Serratia marcescens, Pseudomonas aeruginosa, and Bacteroides fragilis. When a large number of clinical isolates of the above-named bacilli were tested by the agar dilution method, using an inoculum size of one loopful of 10(6) or 10(8) organisms or both per ml, the 70% minimal inhibitory concentrations at the lower inoculum were 0.2, 0.2, 0.4, 0.8, 25, and 0.8 mug/ml, respectively. Its activity appeared to be independent of inoculum size and addition of serum. In these organisms, morphological response of the exposed cells revealed that the bacteriolytic effect of 6059-S was initiated by a concentration equivalent to the minimal inhibitory concentration. 6059-S was markedly bactericidal to both beta-lactamase-producing and -nonproducing strains of Escherichia coli; this was well reflected by its extraordinary stability to microbial beta-lactamase degradation. Administered subcutaneously in mice, 6059-S attained plasma levels and a half-life similar to those of cefazolin and exhibited potent protective efficacy against systemic infections; it also proved to be significantly more effective than either sulbenicillin or piperacillin against Pseudomonas aeruginosa and than either cefazolin or cefmetazole against a variety of other gram-negative bacteria.