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JAC Advance Access published online on June 23, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh339
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received February 23, 2004
Revised April 29, 2004
Accepted May 26, 2004

Original article

Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides

Lorenzo Drago 1*, Elena De Vecchi 1, Lucia Nicola 1, Alberto Colombo 1, Maria Rita Gismondo 1

1 Laboratory of Clinical Microbiology, Department of Clinical Sciences ‘L. Sacco’ Teaching Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy

* To whom correspondence should be addressed. E-mail: microbio{at}unimi.it.


  Abstract

Objective: The in vitro abilities of telithromycin, azithromycin and clarithromycin to select for resistance were compared by testing isolates of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and {beta}-haemolytic streptococci.

Methods: Five strains each of {beta}-lactamase-positive and {beta}-lactamase-negative H. influenzae, {beta}-lactamase-positive and {beta}-lactamase-negative M. catarrhalis, S. pneumoniae, {beta}-haemolytic group A, group C and group G streptococci and three strains of {beta}-lactamase-negative ampicillin-resistant H. influenzae were evaluated. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MIC values were determined after five serial passages on antibiotic-gradient plates and after 10 serial passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of ≥4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on plates containing antibiotics at concentrations equal to the highest NCCLS breakpoints.

Results: Azithromycin, clarithromycin and telithromycin gave a ≥4-fold increase in 20, 20 and 10 streptococcus strains, in 4, 5 and 0 H. influenzae strains and in 2, 7 and 4 M. catarrhalis strains, respectively. After 10 passages on antibiotic-free plates, 21/26 strains for azithromycin, 22/32 for clarithromycin and 1/14 for telithromycin maintained high MIC values. In single-step studies, the frequency of mutations was <10-10 for H. influenzae and M. catarrhalis for telithromycin, azithromycin and clarithromycin. Telithromycin induced mutations at a lower rate than azithromycin and clarithromycin in streptococcal strains.

Conclusion: Telithromycin showed a very limited ability to select for resistance in respiratory pathogens compared with azithromycin and clarithromycin.

Keywords: azithromycin; clarithromycin; ketolides; in vitro selection of resistance; respiratory pathogens.
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