Laboratory Evaluation of BL-S786, a Cephalosporin with Broad-Spectrum Antibacterial Activity

Abstract

Biological and physicochemical properties of BL-S786 were compared with those of cephalothin, cephaloridine, and cefazolin. With few exceptions, BL-S786 was more active than the reference compounds against major gram-negative pathogenic species and its antibacterial spectrum was broader than that of cephalosporins currently available for clinical use. Although BL-S786 was generally less active than the control cephalosporins against gram-positive pathogens, it inhibited their growth at concentrations that should readily be achieved in humans after standard parenteral dosage. Streptococcus faecalis, a species relatively unsusceptible to cephalosporins in general, was an exception. BL-S786 was an effective bactericidal agent for strains of various gram-negative organisms. After intramuscular administration to mice, BL-S786 achieved high concentrations in blood, and its biological half-life was longer than that of the other three cephalosporins.BL-S786 (Fig. 1) is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity. The following is a report on biological and physicochemical properties of BL-S786 in comparison with those pfcephalothin, cephaloridine, and cefazolin, three cephalosporins widely used clinically in the United States and abroad. MATERIALS AND METHODSCephalosporins. BL-S786, 7-[a-(2-aminomethylphenyl)acetamidol-3-[(1-carboxymethyltetrazol-5-ylthio)methyl]-3-cephem-4-carboxylic acid, was synthesized by members of the Product Development Department, Bristol Laboratories (W.

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

“…In our study, BL-S786 was not as active against isolates of Enterobacter spp. as reported elsewhere (3)(4)(5)(6), but the activity of cefamandole, cefoxitin, and cephalothin against these isolates compared well with earlier studies in our laboratory (2) (1).…”

“…Earlier studies compared its activity to that of cephalothin (1,(3)(4)(5), cefamandole, and cefoxitin (1,4,6). In general, our results were similar, but Shadomy et al…”

“…methyl)}-3-cephem-4-carboxylic acid, is a new semisynthetic, parenteral cephalosporin which has been shown to have a broader spectrum of activity in vitro than currently available cephalosporins and comparable activity to investigational drugs such as cefamandole and cefoxitin (1,(3)(4)(5). Its activity against major pathogens, which are a cause of morbidity and mortality among hospitalized patients, warranted further study to confirm these original observations.…”

“…In vivo studies have shown that BL-S786 reached higher peak serum concentrations, that its concentration declined at a slower rate than other cephalosporins, and that it was the most efficacious drug in treatment of infections in mice (5,6).…”

Antibacterial Activity of a New Parenteral Cephalosporin—HR 756: Comparison with Cefamandole and Ceforanide

“…This parenteral drug is a representative of a newer group of cephalosporin antibiotics which shows relative resistance to beta-lactamases of gram-negative bacilli. This group includes cefoxitin, cefamandole (CFM), cefuroxime, and ceforanide (CFN) (7)(8)(9)(10)(11)13). Due in part to this resistance, the newer cephalosporins may demonstrate activity against certain bacteria such as Enterobacter species, Seratia, and indole-positive Proteus strains, the majority of which are ordinarily resistant to other cephalosporin antibiotics.…”