Eijkman-Winkler Center, UMCU, Room G04.614, PO Box 85500, 3508 GA Utrecht, The Netherlands
Keywords: AZD2563, ermB, pneumococcus
Sir,
The treatment of Streptococcus pneumoniae infections is increasingly threatened by the emergence of penicillin- and macrolide-resistant strains. Macrolide-resistant or not fully susceptible S. pneumoniae isolates often contain either ermB, mefE or both determinants. In some cases a mutant ribosomal protein has been detected. Methylation of ribosomal RNA by the ermB-encoded methylase prevents the action of macrolides. The mefE gene encodes a macrolide efflux system. ermB-carrying isolates often have, for unexplained reasons, higher MIC values for macrolides than mefE-containing isolates, and cross-resistance for ermB-harbouring isolates is also higher.1 This would potentially limit the therapeutic usefulness of these antibiotic compounds.
AZD2563 is a new oxazolidinone with activity against Gram-positive bacteria. It acts by interfering with ribosome function and thus protein synthesis,2 as do macrolides. Therefore, the MICs of AZD2563 were determined for ermB-containing isolates.
S. pneumoniae isolates were collected from across Europe. Only one isolate per patient was allowed. The isolates were identified at the source and when deemed clinically significant by local criteria, and sent to the EijkmanWinkler Center using Amies Charcoal Medium transport swabs (Difco, Chicago, IL, USA). Isolates were cultured on blood agar and stored at 70°C using Microbank (Oxoid, Basingstoke, UK) until further testing. Isolate identity was confirmed using optochin discs (Oxoid). Nearly all isolates were obtained from blood culture, sputa, bronchoalveolar lavage and throat swabs. The MICs of erythromycin, clindamycin and AZD2563 were determined using a broth microdilution (Trek Diagnostic Systems, Westlake, OH, USA) method and standard methods defined by the NCCLS.3 The erythromycin-resistant isolates were tested by ermB-specific PCR as described by Sutcliffe et al.4
A total of 77 S. pneumoniae isolates were erythromycin resistant and ermB positive. These isolates came from Belgium (n = 2), Denmark (n = 1), France (n = 12), Italy (n = 5), Luxembourg (n = 21), The Netherlands (n = 5), Poland (n = 3), Portugal (n = 1), Spain (n = 3), Switzerland (n = 4) and Turkey (n = 20). All isolates except six were also clindamycin resistant.
The MICs of AZD2563 for these isolates ranged from 0.12 to 2 mg/L (Table 1). Only one isolate had an MIC of 2 mg/L. Both the MIC50 and MIC90 values for all ermB-positive isolates were 0.5 mg/L. In a surveillance study with a collection of S. pneumoniae isolates with similar origins, the MIC50 and MIC90 values were 0.5 and 1 mg/L, respectively.5
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Acknowledgements
We wish to thank J. Møller, S. Ünal, D. Gür, R. Martin Alvarez, M. Struelens, D. Costa, G.-C. Schito, E. IJzerman, B. Sumerkan, J. Bille, F. Schneider, J. Etienne, J. Ngyen, W. Hryniewicz and L. Spanjaard for the shipment of isolates. We also thank A. Florijn, M. Klootwijk, K. Kusters and S. de Vaal for expert technical help.
Footnotes
* Corresponding author. Tel: +31-30-250-7630; Fax: +31-30-254-1770; E-mail: A.C.Fluit{at}lab.azu.nl
References
1 . Schmitz, F.-J., Verhoef, J., Milatovic, D. & Fluit, A. C. (2001). Treatment options for Streptococcus pneumoniae strains resistant to macrolides, tetracycline, quinolones, or trimethoprim/sulfamethoxazole. European Journal of Clinical Microbiology and Infectious Diseases 20, 8279.[CrossRef][ISI][Medline]
2 . Daly, J. S., Eliopoulos, G. M., Reiszner, E. & Moellering, R. C., Jr (1988). Activity and mechanisms of action of Du 105 and DuP 721, new oxazolidinone compounds. Journal of Antimicrobial Chemotherapy 21, 72130.[Abstract]
3 . National Committee for Clinical Laboratory Standards. (1999). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard M7-A4. NCCLS, Wayne, PA, USA.
4 . Sutcliffe, J., Grebe, T., Tait-Kamradt, A. & Wondrack, L. (1996). Detection of erythromycin-resistant determinants by PCR. Antimicrobial Agents and Chemotherapy 40, 25626.[Abstract]
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Fluit, A. C., Schmitz, F.-J., Verhoef, J. & Milatovic, D. (2002). In vitro activity of AZD2563, a novel oxazolidinone, against European Gram-positive isolates. Journal of Antimicrobial Chemotherapy 50, 2716.
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