In vitro activity of SCE-2787, a new cephalosporin with potent activity against Pseudomonas aeruginosa and members of the family Enterobacteriaceae

Abstract

The in vitro activity of SCE-2787, 7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3- yl)-2-methoxyiminoacetamido]-3-(1-imidazo[1,2-b]pyridazinium)methy l-3- cephem-4-carboxylate, was compared with those of ceftazidime, ceftriaxone, and imipenem against recent clinical isolates. SCE-2787 inhibited 50% of tested isolates of the family Enterobacteriaceae at < or = 0.25 micrograms/ml. SCE-2787 was equally active as or more active than ceftazidime and ceftriaxone against members of the Enterobacteriaceae, with the exception of Proteus vulgaris. The MIC of SCE-2787 at which 90% of the isolates of Pseudomonas aeruginosa were inhibited was 2 micrograms/ml, two- to fourfold lower than those of imipenem and ceftazidime, respectively. SCE-2787, like ceftazidime and imipenem, did not inhibit the majority of strains of Pseudomonas cepacia and Xanthomonas maltophilia. SCE-2787 inhibited beta-hemolytic streptococci at < or = 0.12 micrograms/ml, but it did not inhibit Enterococcus faecalis, Listeria monocytogenes, or the anaerobic species tested. Methicillin-resistant staphylococci required SCE-2787 MICs of > or = 16 micrograms/ml, whereas methicillin-susceptible staphylococci were inhibited by 2 micrograms/ml. No difference between the MICs and MBCs was noted, except for P. aeruginosa, for which there was a fourfold difference. SCE-2787 was active over a pH range of 6 to 8. The inoculum size of 10(5) to 10(7) CFU caused only a twofold change in the MIC for Escherichia coli and Staphylococcus aureus but a 4- to 16-fold change in Enterobacter cloacae and P. aeruginosa. beta-Lactamases from Bush groups 1, 2a, and 2b did not hydrolyze SCE-2787. There was significant hydrolysis of SCE-2787 by the beta-lactamases designated 2b', i.e., TEM-3, TEM-5, TEM-7, and TEM-9, and by the group 2d beta-lactamases. SCE-2787 had poor affinity for group 1 and group 2b enzymes and constitutively produced chromosomal beta-lactamases such as P-99 of Enterobacter cloacae and plasmid-mediated TEM-1 of E. coli. SCE-2787 has in vitro activity comparable to that of current parenteral cephalosporin and is more active against P. aeruginosa and S. aureus.