Cefamandole, a Cephalosporin Antibiotic with an Unusually Wide Spectrum of Activity

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Abstract
The in vitro activity of cefamandole, 7-d-mandelamido-3-(1 methyl-1H-tetrazol-5 yethiomethyl)-3-cephem-4 carboxylic acid, was investigated. The majority of streptococci and pneumococci were inhibited by 0.1 mug/ml. Activity against Staphylococcus aureus was below that of cephalothin, but most strains were inhibited by 0.4 mug/ml. Enterococci were not inhibited by less than 25 mug/ml. Cefamandole was very active against most members of the Enterobacteriaceae, with 70% of Escherichia coli, 86% of Klebsiella pneumoniae, and 88% of Proteus mirabilis inhibited by 1.6 mug/ml. A number of Enterobacter aerogenes, Proteus vulgaris, and Serratia marcescens strains were inhibited by less than 25 mug/ml. Pseudomonas species were resistant. Cefamandole was more active than cephalothin, cephaloridine, or cephalexin against members of the Enterobacteriaceae. Inoculum size and type of medium had variable effects on the minimal inhibitory concentration, depending upon the particular strain tested. Strains of Enterobacter, Serratia, indole-positive Proteus species showed the greatest inoculum effect. Similarly, these species showed a several-fold difference of bactericidal and inhibitory levels. Resistance of cefamandole to hydrolysis by gram-negative beta-lactamase played a partial role in its activity, but some strains that hydrolyzed the agent were susceptible.