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Antimicrobial Agents and Chemotherapy, November 2000, p. 2999-3002, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

In Vitro Activity of the New Ketolide Telithromycin Compared with Those of Macrolides against Streptococcus pyogenes: Influences of Resistance Mechanisms and Methodological Factors

Pascale Bemer-Melchior,1,* Marie-Emmanuelle Juvin,1 Sandrine Tassin,1 Andre Bryskier,2 Gian Carlo Schito,3 and Henri-B. Drugeon1

Department of Microbiology, Laënnec University Hospital, Nantes,1 and Clinical Pharmacology of Anti-Infectives, Hoechst Marion Roussel, Romainville,2 France, Institute of Microbiology, University of Genoa, Genoa, Italy3

Received 19 May 2000/Returned for modification 22 June 2000/Accepted 2 August 2000

One hundred and seven clinical isolates of Streptococcus pyogenes, 80 susceptible to macrolides and 27 resistant to erythromycin A (MIC >0.5 µg/ml), were examined. The erythromycin A-lincomycin double-disk test assigned 7 resistant strains to the M-phenotype, 8 to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLSB) phenotype, and 12 to the constitutive MLSB resistance (cMLSB) phenotype. MICs of erythromycin A, clarithromycin, azithromycin, roxithromycin, and clindamycin were determined by a broth microdilution method. MICs of telithromycin were determined by three different methods (broth microdilution, agar dilution, and E-test methods) in an ambient air atmosphere and in a 5 to 6% CO2 atmosphere. Erythromycin A resistance genes were investigated by PCR in the 27 erythromycin A-resistant isolates. MICs of erythromycin A and clindamycin showed six groups of resistant strains, groups A to F. iMLSB strains (A, B, and D groups) are characterized by two distinct patterns of resistance correlated with genotypic results. A- and B-group strains were moderately resistant to 14- and 15-membered ring macrolides and highly susceptible to telithromycin. All A- and B-group isolates harbored erm TR gene, D-group strains, highly resistant to macrolides and intermediately resistant to telithromycin (MICs, 1 to 16 µg/ml), were all characterized by having the ermB gene. All M-phenotype isolates (C group), resistant to 14- and 15-membered ring macrolides and susceptible to clindamycin and telithromycin, harbored the mefA gene. All cMLSB strains (E and F groups) with high level of resistance to macrolides, lincosamide, and telithromycin had the ermB gene. The effect of 5 to 6% CO2 was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates.

* Corresponding author. Mailing address: Department of Microbiology, Laënnec University Hospital, Bd J. Monod, 44093 Saint-Herblain Cedex 1, France. Phone: (33) 2 40 16 54 57. Fax: (33) 2 40 16 54 55. E-mail: pascale.bemermelchior{at}chu-nantes.fr.

Antimicrobial Agents and Chemotherapy, November 2000, p. 2999-3002, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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