Activity of a novel ketolide A against haemophilus influenzae using in vitro and in vivo pharmacodynamic models

• DOI: 10.1016/j.ijid.2016.02.321
• Publication Date: 2016-03-28T22:03:37Z
• Authors: M. Pandya; M. Rao; T.K. Barmana; R. Sood; S. Dube; R. Venkataramanan
• Keywords: Ketolide; Telithromycin

Background: Haemophilus influenzae causes community-acquired respiratory tract and invasive infections in humans. Resistance to macrolides fluoroquinolones is emerging H. limiting its therapeutic options. In the present study we demonstrated vitro vivo potential of this novel ketolide against influenzae. Methods & Materials: MIC fresh clinical isolates (n=145) (β- lactamase producer, non-producer strains standard ATCC quality control strains) from tertiary care centers India was evaluated using microbroth dilution method (CLSI). Bactericidal time kill kinetics 3 strains. Immunocompromised mouse rat pneumonia model were performed 2 Plasma ELF concentrations estimated HPLC analysis Microbiological method. Results: Ketolide A showed range 0.03 - 4 μg/ml bactericidal different at 4X concentration results comparable with telithromycin. >1 log10 reduction CFU/lungs compared h 100 mg/kg BW PO bid immunocompromised pulmonary infection models. The efficacy correlated accumulation lung tissue much above levels (1-2 μg/ml) upto 8h. Conclusion: Efficacy rodent models high warrants further investigation for treatment infections.