CW-270033, a Novel Pyrrolidinyl-thio Carbapenem, Has Potent Antimicrobial Activity in Vitro and in Vivo

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  • Kim JongMyeung
    Department of Microbiology, Kyungpook National University
  • Ha Jong Ryul
    Central Research Institute, ChoongWae Pharmaceutical Corp.
  • Oh Se Woong
    Central Research Institute, ChoongWae Pharmaceutical Corp.
  • Kim Hong Gi
    Central Research Institute, ChoongWae Pharmaceutical Corp.
  • Lee Jin-Man
    Department of Herb & Food Science, Kyongbuk College of Science
  • Lee Dong Gun
    Department of Microbiology, Kyungpook National University
  • Lee Sang-Han
    Department of Food Science & Technology, Kyungpook National University
  • Kim Jong Guk
    Department of Microbiology, Kyungpook National University

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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.

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