The in vitro and in vivo activity of BO-2727,a carbapenem antibiotic, against resistant clinical isolates of Pseudomonasaeruginosa was studied. The geometric meanMICsagainst three groups of clinical isolates resistant to imipenem, meropenem and both carbapenems were 4.28, 4.08 and 5.44 /zg/ml, respectively. BO-2727 also inhibited multiply antibiotic resistant isolates and laboratory mutants including a nalB-typQ mutant, which showed resistance to antibiotics such as imipenem, meropenem, ceftazidime, and/or ciprofloxacin, at less than 1.56 /ig/ml. Overall, BO-2727 was 4-fold more active than biapenem, meropenem, panipenem and imipenem with an MIC90of less than 6.25/Lig/mlThe presence of basic amino acids in minimal mediumless affected the antipseudomonal activity to a minimal extent, suggesting that BO-2727has diverse penetration routes through the outer membraneother than OprDchannel, which facilitates the diffusion of basic amino acids and carbapenems. The in vitro activity of BO-2727reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results suggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem-and/or meropenem-resistant P. aeruginosa as well as a broad spectrum encompassing Gram-positive and -negative bacteria.Since the discovery of thienamycin1^carbapenem antibiotics are knownto have a broad spectrum encompassing both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. However, the recent problems are the emergenceof carbapenem-resistant P. aeruginosa, in which the mechanismsof resistance are a) deficiency or decreased amount of OprDof the outer membrane, which facilitates the diffusion of carbapenem and basic amino acids2~5), b) nalB mutation responsible for multiple resistance to cephems, quinolones, tetracyclines as well as meropenem5) and c) the evolution of a class B metallo-/Mactamase capable of hydrolyzing carbapenems6).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.