In vitro and in vivo activities of DQ-2556 and its mode of action.
DQ-2556 is a recently developed cephalosporin with a broad spectrum of antibacterial activity against both gram-positive and gram-negative bacteria. Its in vitro activity was roughly comparable to those of cefuzonam and cefpirome and greater than those of ceftazidime, cefepime, and cefclidin against gram-positive bacteria. Against gram-negative bacteria, DQ-2556 showed almost the same activity as those shown by cefpirome and cefepime. The activity was largely unaffected by culture medium pH or the addition of human serum. The protective effect of DQ-2556 in experimental gram-positive pathogen and Escherichia coli infections in mice was greater than those of ceftazidime, cefuzonam, cefepime, and cefclidin and was similar to that of cefpirome. Against Pseudomonas aeruginosa and Acinetobacter calcoaceticus infections, DQ-2556 was more active than cefuzonam and had activity similar to or less than those of ceftazidime, cefpirome, cefepime, and cefclidin. When cells of E. coli were exposed to various concentrations of DQ-2556, filamentous cells were observed at concentrations of 0.0008 micrograms/ml and greater, spheroplasts started to form at 0.025 micrograms/ml, and subsequent cell lysis was observed. The affinity of DQ-2556 to PBP 3 of E. coli, which participates in septum formation, as suggested by morphological observation, was two times greater than that of ceftazidime. DQ-2556 also had high affinities for PBPs 1B and 1A of E. coli. These results suggest that DQ-2556 is worthy for subsequent clinical trials.
Tanaka
M
M
Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Otsuki
M
M
Nishino
T
T
D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002511:Cephalosporins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects; D006602:Hexosyltransferases; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000187:drug effects / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D003470:Culture Media; D046915:Penicillin-Binding Proteins; C050465:DQ 2556; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase