Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation

Nocardicin A, a new monocyclic beta-lactam antibiotic, exerts a comparatively potent antimicrobial activity against gram-negative organisms, especially Pseudomonas aeruginosa, the indole-positive and indole-negative Proteus groups (except Pr. morganii), Serratia marcescens and the Neisseria groups. The in vitro antimicrobial activity of nocardicin A against clinical isolates of Ps. aeruginosa was about twice that of carbenicillin. The mean MICs of nocardicin A for Pr. mirabilis, Pr. rettgeri and Pr. inconstans ranged from 3.13 to 12.5 microgram/ml and were 25 similar to 50 microgram/ml for Pr. vulgaris. Nocardicin A in concentrations of 12.5 similar to 50 microgram/ml inhibited 30 strains (48 percent) of S. marcescens usually resistant to beta-lactam antibiotics. However, nocardicin A had no significant in vitro activity against Staphylococci and Escherichia coli. No cross-resistance was seen between nocardicin A and other beta-lactam antibiotics. This antibiotic was stable to beta-lactamase. The in vitro activity of nocardicin A against Ps. aeruginosa and Pr. mirabilis was greatly influenced by the assay media used. Nocardicin A was bactericidal and appeared to act synergistically with serum bactericidal factors against Ps. aeruginosa and with polymorphonuclear leukocytes against Ps. aeruginosa, E. coli and Pr. vulgaris. The bactericidal activity of nocardicin A against the above 3 organisms, therefore, increased markedly in the presence of fresh serum and polymorphonuclear leukocytes.