HR 756, a Highly Active Cephalosporin: Comparison with Cefazolin and Carbenicillin

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Abstract
HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus spp. (indole positive), Enterobacter spp., Salmonella typhi, Serratia marcescens, Providencia stuartii , and Staphylococcus aureus . In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of Streptococcus pyogenes , Lancefield group D streptococci, and Neisseria gonorrhoeae ; with ampicillin against Haemophilus influenzae ; and with cefoxitin against Bacteriodes fragilis . HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against S. pyogenes ; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms ( P. aeruginosa and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 μg/ml. A series of seven transfers of selected strains of E. coli, Klebsiella spp., S. aureus , and P. aeruginosa through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium.