JAC Advance Access published online on April 29, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh169
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Institute of Medical Microbiology, National Reference Centre
for Streptococci, Pauwelsstrasse 30,
52074 Aachen, Germany
* To whom correspondence should be addressed. E-mail: reinert{at}rwth-aachen.de.
Ketolides are a new class of semi-synthetic agents
derived from erythromycin A designed to overcome erythromycin A
resistance in Streptococcus pneumoniae. Telithromycin
(HMR 3647) is the first member of this new class to be approved
for clinical use. Cethromycin (ABT-773) has been developed up to
Phase III, but its further development seems questionable at the
moment. Other ketolides are only in the first stages of preclinical
development and may not be available within the foreseeable future.
Ketolide compounds inhibit bacterial protein synthesis by interacting
with the peptidyl transferase site of the 50S ribosomal subunit,
and interact closely with domains II at A752 and V at A2058 and
A2059 of the 23S rRNA. These compounds also inhibit the formation
of the 50S subunit of the ribosome. Ketolides show good activity
against the Gram-positive bacteria responsible for respiratory tract
infections including penicillin G- and erythromycin
A-resistant S. pneumoniae. The 15 clinical
trials with telithromycin published to date include four randomized, double-blind
comparative trials and three open-label studies in community-acquired
pneumonia, three randomized double-blind trials in acute exacerbation
of chronic bronchitis, two randomized double-blind trials in pharyngitis,
and two double-blind comparative trials and one open-label trial
in acute maxillary sinusitis. Clinical response rates were favourable
in all clinical trials, with eradication rates in patients with pneumococcal
bacteraemia and penicillin G- and erythromycin A-resistant pneumococcal
infections at least as high as those of comparators. As resistance
to macrolides continues to emerge, the availability of other ketolides
besides telithromycin and a development programme for the application
of ketolides in children would appear to be warranted to obtain
a new class of antibiotics that may one day replace macrolides.
Review
Clinical efficacy of ketolides in the treatment
of respiratory
tract infections
Abstract 
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