BL-S786 (Ceforanide), a New Parenteral Cephalosporin: In Vitro Studies

Abstract

BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 ,.g/ml, it inhibited greater than 75% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Essentially no activity was observed against isolates of Serratia marcescens, and only miniimal activity was observed against Enterobacter spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except S. aureus and S. pyogenes. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms. G-resistant, and those isolates inhibited by 0.10 ,ug or less per ml were selected as penicillin G-susceptible, as determined by a broth dilution method. All gramnegative bacilli were cultured from blood specimens obtained from cancer patients at this institution. Gram-positive cocci were cultured from various sites from hospitalized patients, some of whom did not have cancer.All isolates of gram-negative bacilli and of S. aureus were incubated in Mueller-Hinton broth at 370C for 18 h. Isolates of S. pyogenes and S. pneumoniae were incubated in tryptose-phosphate broth in a 370C C02 incubator for 18 h.

Evaluation of ceforanide as treatment for staphylococcal and streptococcal endocarditis

“…One patient developed eosinophilia (25%) and asymptomatic hepatitis with a rise in hepatocellular enzymes to seven times the normal level by week 3 of therapy. Upon admission his liver function assays were elevated, but they decreased to near-normal levels during the first 10 hospital days before they increased again. The second patient developed eosinophilia (19%), mild neutropenia, erythema multiforme, and arthritis during week 3 of therapy.…”

“…Two patients were withdrawn from the study; one was transferred to another hospital and a second patient was infected with a tolerant organism against which adequate serum bactericidal activity could not be achieved. (10). The clinical significance of tolerance is still being debated, but it may be more important in patients with endocarditis for whom bactericidal therapy is considered essential (2,3,9).…”