A novel ketolide RBx 14255 with activity against multi-drug resistant Streptococcus pneumoniae.

We present a novel ketolide RBx14255, a semi-synthetic macrolide derivative obtained by derivatization of clarithromycin, for its in vitro and in vivo activity against sensitive and macrolide-resistant S. pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae including in-house generated telithromycin-resistant strain (S. pneumoniae 3390 NDDR). RBx 14255 showed potent protein synthesis inhibition against telithromycin-resistant S. pneumoniae 3390 NDDR. The binding affinity of RBx 14255 towards ribosome was found to be more than 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 of S. pneumoniae 3390 NDDR strains. The ED50 of RBx 14255 was 3.12 mg/kg against S. pneumoniae ATCC 6303 in murine pulmonary infection model. In addition, RBx 14255 showed 100% survival of animals in murine systemic infection caused by macrolide-resistant S. pneumoniae 3390 NDDR at 100 and 50 mg/kg, QID. RBx 14255 showed favorable pharmacokinetic properties and comparable to telithromycin.
PMID: 24550341 [PubMed - as supplied by publisher]

Source: Antimicrobial Agents and Chemotherapy - February 18, 2014 Category: Microbiology Authors: Raj VS, Barman TK, Kalia V, Purnapatre K, Dube S, Ramkumar G, Bhateja P, Mathur T, Chaira T, Upadhyay DJ, Surase YB, Venkataramanan R, Chakrabarti A, Das B, Bhatnagar PK Tags: Antimicrob Agents Chemother Source Type: research