In-vitro antibacterial activity of DQ-2556 and its stability to various beta-lactamases.
DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram-positive and -negative organisms. The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime. DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime. With the exception of Ps. aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC. DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps. aeruginosa. DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases. The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins. The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells.
Fujimoto
T
T
Episome Institute, Seta-gun, Japan.
Watanabe
M
M
Inoue
M
M
Mitsuhashi
S
S
D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004355:Drug Stability; D004755:Enterobacteriaceae / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism; D000097572:Cefpirome
D002442:Ceftazidime; D002511:Cephalosporins; D001618:beta-Lactamases; D000097572:Cefpirome; C050465:DQ 2556