JAC Advance Access published online on March 31, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh178
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Medical
Microbiology, Medical School, University of Edinburgh, Edinburgh
EH8 9AG, UK;
* Corresponding author. E-mail: fwalsh{at}staffmail.ed.ac.uk.
Received 31 October 2003
; revised 2 February 2004
; accepted 10 February 2004
Objectives: The first objective was
to investigate the in vitro activity of telithromycin
against respiratory tract pathogens in comparison with other antimicrobial
agents. The second objective was to identify the influence of the erm(B) and mef(A) genes on the
susceptibility of Streptococcus pneumoniae to telithromycin. Methods: The in vitro activity
of telithromycin against S. pneumoniae, Moraxella
catarrhalis and Haemophilus influenzae, isolated
from the UK and 40 macrolide-resistant S. pneumoniae from
four different countries was compared with a variety of antimicrobial
agents. The 140 isolates were examined for the presence of the erm(B) and mef(A) genes. The impact
of 5% CO2 on susceptibility testing was also
investigated. Results: Telithromycin showed greatest activity
against S. pneumoniae, but also had good activity
against M. catarrhalis and H. influenzae,
which was independent of their resistance profiles to other antibiotics.
The MIC90 of telithromycin for S. pneumoniae was
0.12 mg/L, which was 64-fold lower than the lowest macrolide MIC;
21% of the S. pneumoniae were macrolide
resistant. Thirty-eight per cent of the macrolide-resistant strains
were erm(B)-positive and 62% were mef(A)-positive, but no strain
contained both genes. The activity of telithromycin was similar
to that of azithromycin against both M. catarrhalis and H. influenzae, Erythromycin was slightly less active:
1% and 8% of M. catarrhalis and H. influenzae, respectively, were resistant to erythromycin,
but none were resistant to telithromycin. Five per cent of the S. pneumoniae strains and 4% of the H. influenzae strains changed from telithromycin
susceptible to non-susceptible entirely because of the incubation
conditions. The MIC50s and MIC90s of S.
pneumoniae, M. catarrhalis and H.
influenzae increased by one dilution when incubated in CO2. Conclusions: Telithromycin has shown high in vitro activity against S. pneumoniae,
including those strains that are macrolide susceptible and resistant
as well as M. catarrhalis and H. influenzae.
This study has also demonstrated that there is no cross-resistance
between erythromycin and telithromycin. The impact of 5% CO2 on
susceptibility testing should be investigated further before providing
definite guidelines on telithromycin susceptibility testing.
Keywords: resistance, erm(B), ketolides
Comparative in vitro activity
of telithromycin against
macrolide-resistant and -susceptible Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus
influenzae
2 Aventis Pharma
Ltd, Kings Hill, West Malling, Kent ME19 4AH, UK
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