IN-VITRO ACTIVITY OF SCE-2787, A NEW CEPHALOSPORIN WITH POTENT ACTIVITY AGAINST PSEUDOMONAS-AERUGINOSA AND MEMBERS OF THE FAMILY ENTEROBACTERIACEAE

The in vitro activity of SCE-2787, [1,2-b]pyridazinium)methyl-3-cephem -4-carboxylate, was compared with those of ceftazidime, ceftriaxone, a nd imipenem against recent clinical isolates. SCE-2787 inhibited 50% o f tested isolates of the family Enterobacteriaceae at less than or equ al to 0.25 mu g/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 mu g/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 maltop hilia. SCE-2787 inhibited beta-hemolytic streptococci at less than or equal to 0.12 mu g/ml, but it did not inhibit Enterococcus faecalis, L isteria monocytogenes, or the anaerobic species tested. Methicillin-re sistant staphylococci required SCE-2787 MICs of greater than or equal to 16 mu g/ml, whereas methicillin-susceptible staphylococci were inhi bited by 2 mu g/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 Escherich ia coli and Staphylococcus aureus but a 4- to 16-fold change in Entero bacter cloacae and P. aeruginosa. beta-Lactamases from Bush groups 1, 2a, and 2b did not hydrolyze SCE-2787. There was significant hydrolysi s 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 pro duced 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 ac tive against P. aeruginosa and S. aureus.