The PROTEKT global study (year 4) demonstrates a continued lack of resistance development to telithromycin in Streptococcus pneumoniae

David J. Farrell* and David Felmingham

GR Micro Limited, 7–9 William Road, London NW1 3ER, UK


* Corresponding author. Tel: +44-20-73804469; Fax: +44-20-73887324; E-mail: d.farrell{at}grmicro.co.uk

Keywords: S. pneumoniae , ketolides , macrolides

Sir,

In the early 1990s, against a background of already worrying rates of erythromycin resistance among isolates of Streptococcus pneumoniae, further sharp increases in the prevalence of macrolide resistance were observed 1 to 2 years after the introduction of the macrolides azithromycin and clarithromycin into Europe and the USA.1 This increase strongly correlated with the consumption of these antibiotics in most countries and overall.1 A more recent study in Portugal, using molecular epidemiological investigation, demonstrated that the emergence of macrolide resistance had a high correlation with azithromycin usage in that country.2

Telithromycin is the first clinically available ketolide, a new class of antimicrobial within the macrolide–lincosamide–streptogramin B (MLSB) group, which is characterized by potent in vitro and clinical activity against Gram-positive cocci including MLSB and multidrug-resistant strains.3 Telithromycin was introduced into clinical practice in Germany in October 2001, followed shortly after by Italy, Spain, Mexico, Brazil and France. The PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study is a global, longitudinal, international surveillance programme established in 1999 to study the antimicrobial susceptibility of common bacterial pathogens associated with community-acquired respiratory tract infections, which has now completed its fourth year. One of the primary goals of PROTEKT is to monitor the development of telithromycin resistance post-introduction. In this correspondence, we update our analysis of the first 3 years of this study with year 4 data.4

MICs of telithromycin were determined using CLSI (NCCLS) standard methods.5 Genotyping and serotyping were performed as described previously.6 Statistical analysis was performed using GraphPad Prism software (GraphPad Software, Inc., San Diego, CA, USA). One-way ANOVA was used to examine overall variance of means and Tukey's multiple comparison test was used to compare the variance of each year with each of the other 3 years.7

During the four respiratory seasons (1999–2003), 21 out of 20 750 (0.1%) S. pneumoniae isolates demonstrated low-level resistance to telithromycin (MICs of 4–8 mg/L) (Table 1). Among these 21 isolates, 13 different MLST types and seven different serotypes were identified. In addition, clonally-related strains could not be found consistently in the same centres in any of the four years studied. Nineteen of the 21 isolates harboured erm(B), and two isolates harboured both erm(B) and mef(A). The MIC distribution did not change significantly over the 4 years (P = 0.75), and the MIC distribution in any one year was not significantly different from any other year (P > 0.05 for each year pair). In the 4 years the study has been conducted in the countries described above, more than 5 million courses of telithromycin have been prescribed since its introduction in 2001.


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Table 1. Distribution of telithromycin MICs in 20 750 isolates of Streptococcus pneumoniae isolated from the PROTEKT global antimicrobial surveillance studies, 1999–2003

 
Unlike the rapid increase in resistance that occurred within 2 years of the introduction of azithromycin and clarithromycin, resistance to telithromycin amongst isolates of S. pneumoniae has not increased since its introduction in 2001.1,4 However, as with any antimicrobial, the development of resistance needs to be carefully monitored.

Acknowledgements

We are grateful to our colleagues worldwide for the supply of bacterial isolates as part of the PROTEKT study and the GR Micro PROTEKT team who performed the MIC determinations. Sanofi-Aventis is acknowledged for their financial support of the PROTEKT study.

References

1. Baquero F. Evolving resistance patterns of Streptococcus pneumoniae: a link with long-acting macrolide consumption? J Chemother 1999; 11 Suppl 1: 35–43.[ISI][Medline]

2. Dias R, Caniça M. Emergence of invasive erythromycin-resistant Streptococcus pneumoniae strains in Portugal: contribution and phylogenetic relatedness of serotype 14. J Antimicrob Chemother 2004; 54: 1035–9.[Abstract/Free Full Text]

3. Leclercq R. Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin. J Antimicrob Chemother 2001: 48 Topic 1: 9–23.[Abstract/Free Full Text]

4. Farrell DJ, Felmingham D. Activities of telithromycin against 13,874 Streptococcus pneumoniae isolates collected between 1999 and 2003. Antimicrob Agents Chemother 2004; 48: 1882–4.[Abstract/Free Full Text]

5. National Committee for Clinical Laboratory Standards (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA, USA, 2000.

6. Farrell DJ, Jenkins SG, Reinert RR. Global distribution of Streptococcus pneumoniae serotypes isolated from paediatric patients during 1999–2000 and the in vitro efficacy of telithromycin and comparators. J Med Microbiol 2004; 53: 1109–17.[Abstract/Free Full Text]

7. GraphPad. The Prism Guide to Interpreting Statistics. http://www.graphpad.com/articles/interpret/ANOVA/choosing_test.htm (1 July 2005, date last accessed).





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