Comparison of in vivo nephrotoxicity in the rabbit by a pyrrolidinyl-thio carbapenem CW-270031

CW-270031 is a novel synthesized carbapenem antibiotic with a broad antimicrobial activity. Carbapenem antibiotics are well known for their nephrotoxicity. In this study, we evaluated the nephrotoxicity potential of this compound in rabbits, which are known for being more sensitive than other animals to renal insult. CW-270031 was administered to NZW male rabbits via an ear vein (200 mg/kg, single injection). Blood samples were collected on 2, 3, and 4 days after treatment. Urea nitrogen and creatinine in plasma were quantified. Four days after the treatment, all animals were autopsied and histopathological examinations were performed on their kidneys, revealing that cephaloridine and imipenem were highly nephrotoxic, and cefazolin had mild renal toxicity, whereas CW-270031 as well as meropenem and tienam had no toxicity to the kidney. The present findings suggest that CW-270031 is a potential carbapenem antibiotic with no nephrotoxicity.