La telithromycine (Ketek~R),une innovation pour la prise en charge des infections respiratories communautaires de l'adulte

摘要

After many years of susceptibility of S.pneumoniae and S.pyogenes of beta-lactams and macrolide,bacterial resistance emerged to these antibiotic classes and has been disseminated world wide.Search for new compounds or derivatives of preceding antibiotics has resulted in the development of a new class,the ketolides,derivatives of erythromycin A.The first molecule of this class is telithromycin,characterised by:1) a substitution in position C11-C12 by a carbamate;2) an improved stability in acidic media;3) non-induction of resistance to macrolides;4) antibacterial activity characterised by a wide antibacterial spectrum,an improved activity against H.influenzae compared to macrolides,and a notable activity against S.pyogenes and S.pneumoniae resistant to macrolides.Moreover telithromycin is not affected by 2 mechanisms of resistance seen in S.pneumoniae (mefE+ermB).Pharmacodynamics of the drug indicated that the ratio AUC/MIC is predicative of anti bacterial activity and a long post-antibiotic affect has been found against S.pneumoniae.Bio-availability of telithromycin is 57% by oral route and elimination is mainly achieved by entero-hepatic route.Plasma kinetics studies showed a peak of 1.9 mg/l and an elimination half-life of 10-12 hours.Protein binding occurs in plasma to albumin and for 12 to 30% to alpha1-glycoprotein;tissue distribution of the drug permits to achieve high concentrations in respiratory tissues,fluids and intracellularly.It clinical efficacy has been conformed in community-acquired pneumonia,in acute exacerbations of chronic bronchitis.Side effects seen during Phase III studies were limited and interactions with enzymes of cytochrome P450 were reversible.These was no alteration of kinetics of warfarin,theophyllin,paroxetin when telithromycin was co-administered