Document Detail

Ketolides in the treatment of respiratory infections.
MedLine Citation:
PMID:  11866679     Owner:  NLM     Status:  MEDLINE    
The ketolides are a new class of macrolides specifically designed to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A. There are currently two ketolides in the late stages of clinical development in the US (telithromycin [HMR-364, Kelek; Aventis] and ABT-773 [Abbot Laboratories]), as well as newer compounds in earlier stages of testing. Ketolides have a mechanism of action very similar to that of erythromycin A. They potently inhibit protein synthesis by interacting close to the peptidyl transferase site of the bacterial 50S ribosomal subunit. Ketolides bind to ribosomes with higher affinity than macrolides. The ketolides exhibit good activity against Gram-positive and some Gram-negative aerobes and have are active against macrolide-resistant Streptococcus species, including most mef A and erm B strains of Streptococcus pneumoniae. Ketolides have pharmacokinetics which allow once-daily dosing and extensive tissue distribution with very high uptake into respiratory tissues and fluids relative to serum. Evidence suggests the ketolides are primarily metabolised by the cytochrome P450 (CYP) enzyme system in the liver and that elimination is a combination of biliary, hepatic and urinary excretion. Clinical trial data are only available for telithromycin and have focused on respiratory tract infections (RTIs) including community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), sinusitis and streptococcal pharyngitis. Bacteriological and clinical cure rates have been similar to comparators. Ketolides have similar safety profiles to the newer macrolides. In summary, early clinical trials support the clinical efficacy of the ketolides in common RTIs, including activity against macrolide-resistant pathogens.
George G Zhanel; Daryl J Hoban
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on pharmacotherapy     Volume:  3     ISSN:  1465-6566     ISO Abbreviation:  Expert Opin Pharmacother     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-27     Completed Date:  2002-09-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100897346     Medline TA:  Expert Opin Pharmacother     Country:  England    
Other Details:
Languages:  eng     Pagination:  277-97     Citation Subset:  IM    
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Canada.
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MeSH Terms
Anti-Bacterial Agents / adverse effects,  economics,  pharmacokinetics,  pharmacology,  therapeutic use*
Bacteria / drug effects
Clinical Trials as Topic
Drug Interactions
Drug Resistance, Microbial
Erythromycin / adverse effects,  analogs & derivatives*,  pharmacokinetics,  pharmacology,  therapeutic use*
Respiratory Tract Infections / drug therapy*,  economics,  microbiology
Tissue Distribution
Reg. No./Substance:
0/Anti-Bacterial Agents; 114-07-8/Erythromycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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