Journal Article

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

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

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 2, pages 542-545
Published in print August 2004 | ISSN: 0305-7453
Published online August 2004 | e-ISSN: 1460-2091 | DOI:
Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides

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  • Medical Oncology
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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 β-haemolytic streptococci.

Methods: Five strains each of β-lactamase-positive and β-lactamase-negative H. influenzae, β-lactamase-positive and β-lactamase-negative M. catarrhalis, S. pneumoniae, β-haemolytic group A, group C and group G streptococci and three strains of β-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

Journal Article.  1939 words. 

Subjects: Medical Oncology ; Critical Care

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