title: 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.
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D002513:Cephamycins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004352:Drug Resistance, Microbial; D006207:Half-Life; D006801:Humans; D051379:Mice; D009070:Moxalactam; D013045:Species Specificity
chemical_list: D002511:Cephalosporins; D002513:Cephamycins; D009070:Moxalactam