title: CW-270033, a novel pyrrolidinyl-thio carbapenem, has potent antimicrobial activity in vitro and in vivo.
abstract: CW-270033, an injectable carbapenem, is a novel, synthesized pyrrolidinyl-thio carbapenem. In the present study, the in-vitro and in-vivo antibacterial activities of CW-270033 against wild-type strains and clinical isolates were compared with those of imipenem and meropenem. CW-270033 was more active than imipenem against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) clinical isolates, but was slightly less active than meropenem. Against the Gram-positive clinical isolates methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), CW-270033 was slightly more active than meropenem, but was less active than imipenem. CW-270033 displayed potent in-vivo activity against E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus SMITH in the mouse systemic infection model; the efficacy of CW-270033 in this model was 2--7 fold higher than that of meropenem. This activity was comparable to the in-vitro activity of CW-270033. An intravenous injection of CW-270033 showed that the half-life of CW-270033 in serum in mice was about 20 min, which was about two times that of meropenem. CW-270033 was also found to be resistant to hydrolysis by the mouse renal dehydropeptidase I (DHP-I) enzyme.
authors.affiliation: Department of Microbiology, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: JongMyeung
authors.initials: J
authors.lastname: Kim
authors.forename: Jong Ryul
authors.initials: JR
authors.lastname: Ha
authors.forename: Se Woong
authors.initials: SW
authors.lastname: Oh
authors.forename: Hong Gi
authors.initials: HG
authors.lastname: Kim
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Lee
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong Guk
authors.initials: JG
authors.lastname: Kim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001424:Bacterial Infections / Q000382:microbiology / Q000517:prevention & control*; D015780:Carbapenems / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015377:Cilastatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007275:Injections, Intravenous; D000077731:Meropenem; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011759:Pyrrolidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013845:Thienamycins / Q000008:administration & dosage / Q000494:pharmacology; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; C522104:CW-270033; D015780:Carbapenems; D011480:Protease Inhibitors; D011759:Pyrrolidines; D013845:Thienamycins; D015377:Cilastatin; D000077731:Meropenem