7-[α-(1-Methyl-4-Pyridinothio)-Acetamido] Cephalosporanic Acid

Abstract

7-[α-(1-Methyl-4-pyridiniothio)-acetamido] cephalosporanic acid, referred to herein as BL-S 217, is a new broad-spectrum semisynthetic cephalosporin that offers several advantages over cephalothin. A comparison of the activity in vitro of these antibiotics indicates that BL-S 217 is about eightfold more effective against Streptococcus pyogenes and Diplococcus pneumoniae . Against gram-negative bacteria, BL-S 217 possesses a broader antibacterial spectrum than cephalothin, particularly against members of the Enterobacteriaceae family; e.g., BL-S 217 inhibited over 20% more strains of both Escherichia coli and Klebsiella than cephalothin and also showed some advantage in tests against Salmonella and Enterobacter . Overall, of 208 strains of Enterobacteriaceae tested, 172 were susceptible to BL-S 217 compared to 149 for cephalothin. BL-S 217 was less bound to human serum proteins than cephalothin and gave higher peak blood levels in mice after intramuscular administration. The LD ₅₀ of BL-S 217 in mice after subcutaneous administration was in excess of 4,000 mg/kg. When administered by the same route to mice experimentally infected with cephalothin-sensitive bacterial strains, this new cephalosporin was 20 times more effective than cephalothin in S. pyogenes and D. pneumoniae infections and 3 to 4 times more efficacious in an E. coli infection. Its therapeutic efficacy was comparable to that of cephalothin in infections produced by strains of Staphylococcus aureus, Klebsiella pneumoniae , and Proteus mirabilis .