CEPHAMYCIN DERIVATIVES: COMPARISON OF THE IN VITRO AND IN VIVO ANTIBACTERIAL ACTIVITIES OF SQ 14, 359, CS-1170, AND CEFOXITIN

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SQ 14, 359 is a new cephamycin-type (7α-OCH₃) antibiotic belonging to a series containing a 7α-ureidoacetyl substituent. The compound is the most potent extended spectrum derivative of this type yet reported, surpassing CS-1170 and cefoxitin by a wide margin. This activity in vitro which extends throughout the Enterobacteriaceae is particularly prominent against Gram-negative organisms that are producers of "cephalosporinase-type" β-lactamases such as Enterobacter, Serratia, Citrobacter and indole-positive Proteus species. Superior activity also is demonstrated in vitro against streptococci, β-lactamase-producing staphylococci, Haemophilus influenzae, Neisseria gonorrhoeae, and many Gram-negative pathogens resistant to aminoglycoside antibiotics. Experimental chemotherapeutic studies have confirmed these observations in wound and selected systemic infections in mice as well as acute pyelonephritis and meningitis in rats. The pharmacokinetics for each drug including antibiotic bound to serum was similar in both mice and rats. The pharmacokinetic profile in blood and cerebrospinal fluid favored SQ 14, 359.