A novel ketolide, RBx 14255, with activity against multidrug-resistant Streptococcus pneumoniae.

Autor:	Raj VS; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India vethakkani.raj.g6@dsin.co.in., Barman TK; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Kalia V; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Purnapatre K; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Dube S; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., G R; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Bhateja P; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Mathur T; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Chaira T; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Upadhyay DJ; Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Surase YB; Department of Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Venkataramanan R; Department of Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Chakrabarti A; Department of Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Das B; Department of Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India., Bhatnagar PK; Department of Chemistry, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Gurgaon, India.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2014 Aug; Vol. 58 (8), pp. 4283-9. Date of Electronic Publication: 2014 Feb 18.
DOI:	10.1128/AAC.01589-13
Abstrakt:	We present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for its in vitro and in vivo activities against sensitive and macrolide-resistant Streptococcus pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae, including an in-house-generated telithromycin-resistant strain (S. pneumoniae 3390 NDDR). RBx 14255 also showed potent protein synthesis inhibition against telithromycin-resistant S. pneumoniae 3390 NDDR. The binding affinity of RBx 14255 toward ribosomes was found to be more than that for other tested drugs. The in vivo efficacy of RBx 14255 was determined in murine pulmonary infection induced by intranasal inoculation of S. pneumoniae ATCC 6303 and systemic infection with S. pneumoniae 3390 NDDR strains. The 50% effective dose (ED50) of RBx 14255 against S. pneumoniae ATCC 6303 in a murine pulmonary infection model was 3.12 mg/kg of body weight. In addition, RBx 14255 resulted in 100% survival of mice with systemic infection caused by macrolide-resistant S. pneumoniae 3390 NDDR at 100 mg/kg four times daily (QID) and at 50 mg/kg QID. RBx 14255 showed favorable pharmacokinetic properties that were comparable to those of telithromycin. (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu