title: [In vitro and in vivo activities of sulopenem compared with those of imipenem and cephalosporins].
abstract: The in vitro and in vivo antibacterial activities of sulopenem (CP-70,429),a new parenteral penem antibiotic, were compared with those of imipenem (IPM), flomoxef, cefuzonam (CZON) and cefotaxime. Sulopenem possessed broad-spectrum activities against Gram-positive bacteria and Gram-negative bacteria. Antibacterial activities of sulopenem against methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae were equivalent to or somewhat superior to those of IPM. Against members of the family Enterobacteriaceae, sulopenem was 4- to 260-fold more active than reference antibiotics with broad-spectra. In a killing kinetics study for Haemophilus influenzae, sulopenem showed a 99.9% decrease of viable cells after 8 hours at a concentration of 0.20 micrograms/ml. This effect was obtained at a concentration 8-fold lower than that of IPM. The protective effects of sulopenem in murine experimental systemic infections were superior to those of imipenem/cilastatin. In murine experimental mixed infection with Escherichia coli and Bacteroides fragilis, sulopenem had lower ED50, in other words stronger antimicrobial activities than IPM. The therapeutic effect of sulopenem are related well with its MIC value. In guinea pigs experimental lung infection with Klebsiella pneumoniae, sulopenem was more effective than CZON or cefotiam.
authors.affiliation: Department of Microbiology, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagashima
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: H
authors.initials: H
authors.lastname: Shimohira
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001442:Bacteroides Infections / Q000188:drug therapy; D001441:Bacteroides fragilis; D002439:Cefotaxime / Q000494:pharmacology; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000188:drug therapy; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006168:Guinea Pigs; D015378:Imipenem / Q000494:pharmacology; D007710:Klebsiella Infections / Q000188:drug therapy; D007769:Lactams; D008171:Lung Diseases / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D013845:Thienamycins / Q000494:pharmacology; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D007769:Lactams; D013845:Thienamycins; C082897:sulopenem; D015378:Imipenem; C049934:cefuzonam; D015296:Ceftizoxime; D002439:Cefotaxime; C045693:flomoxef