Ketolides: pharmacological profile and rational positioning in the treatment of respiratory tract infections

Expert Opinion on Pharmacotherapy
Françoise Van BambekePaul M Tulkens

Abstract

Ketolides differ from macrolides by removal of the 3-O-cladinose (replaced by a keto group), a 11,12- or 6,11-cyclic moiety and a heteroaryl-alkyl side chain attached to the macrocyclic ring through a suitable linker. These modifications allow for anchoring at two distinct binding sites in the 23S rRNA (increasing activity against erythromycin-susceptible strains and maintaining activity towards Streptococcus pneumoniae resistant to erythromycin A by ribosomal methylation), and make ketolides less prone to induce methylase expression and less susceptible to efflux in S. pneumoniae. Combined with an advantageous pharmacokinetic profile (good oral bioavailability and penetration in the respiratory tract tissues and fluids; prolonged half-life allowing for once-a-day administration), these antimicrobial properties make ketolides an attractive alternative for the treatment of severe respiratory tract infections such as pneumonia in areas with significant resistance to conventional macrolides. For telithromycin (the only registered ketolide so far), pharmacodynamic considerations suggest optimal efficacy for isolates with minimum inhibitory concentration values < or = 0.25 mg/l (pharmacodynamic/pharmacokinetic breakpoint), calling f...Continue Reading

References

Apr 1, 1977·Antimicrobial Agents and Chemotherapy·N E Allen
Sep 1, 1989·Antimicrobial Agents and Chemotherapy·H A Kirst, G D Sides
Oct 23, 1997·Antimicrobial Agents and Chemotherapy·C AgouridasJ F Chantot
Aug 4, 1998·Antimicrobial Agents and Chemotherapy·D VazifehM T Labro
Sep 16, 1998·Clinical Therapeutics·M S NiedermanR Popovian
May 29, 1999·The American Journal of Medicine·M D Poole
Mar 20, 2001·Annals of Internal Medicine·R J CooperUNKNOWN Centers for Disease Control
Apr 4, 2001·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·A Bryskier
Jun 1, 2001·Annals of Emergency Medicine·R J CooperUNKNOWN Centers for Disease Control and Prevention
Jun 5, 2001·The Journal of Antimicrobial Chemotherapy·O A KhairR Wise
Jun 22, 2001·The Journal of Antimicrobial Chemotherapy·C Slater-RadostiD D Jaworski
Jun 22, 2001·The Journal of Antimicrobial Chemotherapy·M GuittonA Bonnefoy
Sep 22, 2001·The Journal of Antimicrobial Chemotherapy·S Douthwaite, W S Champney
Sep 22, 2001·The Journal of Antimicrobial Chemotherapy·M R HammerschlagC M Bébéar
Oct 16, 2001·Antimicrobial Agents and Chemotherapy·C Muller-SerieysA Andremont
Oct 17, 2001·Pharmacotherapy·D T BeardenK W Garey
Sep 27, 2002·Current Opinion in Pharmacology·Angela M Nilius, Zhenkun Ma
Nov 5, 2002·The European Respiratory Journal·G J HuchonP M Preux
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Ken B WaitesLynn B Duffy
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·Cristina SeralFrançoise Van Bambeke
Jul 3, 2003·Journal of Bacteriology·Rita BerisioAda Yonath
Aug 15, 2003·The Journal of Antimicrobial Chemotherapy·Fiona WalshSebastian Amyes
Aug 20, 2003·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·C CarbonP Decosta
Jan 9, 2004·Infectious Disease Clinics of North America·Stéphane CarrynPaul M Tulkens
Jan 27, 2004·Antimicrobial Agents and Chemotherapy·James H JorgensenCynthia G Whitney

❮ Previous
Next ❯

Citations

Dec 20, 2003·Lancet·Thomas M File
Feb 7, 2012·Biochemistry·Mariya MorarGerard D Wright
Apr 23, 2011·The Journal of Antimicrobial Chemotherapy·Takafumi SatoNaomasa Gotoh
Nov 26, 2009·Antimicrobial Agents and Chemotherapy·Hidetoshi FuruieJingoro Shimada
May 29, 2009·Expert Opinion on Therapeutic Patents·Giovanna PoceMariangela Biava
Jul 22, 2010·Expert Opinion on Therapeutic Patents·Herbert A Kirst
Feb 6, 2016·Expert Review of Anti-infective Therapy·Françoise Van Bambeke, Paul M Tulkens
Jan 19, 2008·Expert Opinion on Pharmacotherapy·Javier AspaFelipe Rodríguez de Castro
Mar 1, 2009·Expert Opinion on Drug Discovery·Georg Schitter, Tanja M Wrodnigg
Aug 27, 2014·Expert Opinion on Investigational Drugs·Nafsika H Georgopapadakou
Dec 28, 2010·Bioorganic & Medicinal Chemistry Letters·Mirjana Bukvić KrajačićNedjeljko Kujundžić
Nov 19, 2013·Molecular Cell·Pulkit GuptaNora Vázquez-Laslop
Apr 18, 2013·Bioorganic & Medicinal Chemistry Letters·Jie-Wei JiangQi-Dong You
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Lisa S McCoyYitzhak Tor
Oct 21, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Rajesh ChavanMahesh Patel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.