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Antimicrobial Agents and Chemotherapy, March 2006, p. 893-898, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.893-898.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of Efflux on Telithromycin and Macrolide Susceptibility in Haemophilus influenzae

Tatiana Bogdanovich,¹ Bülent Bozdogan,² and Peter C. Appelbaum^1*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,¹ Mikrobiyoloji ve Klinik Mikrobiyoloji AD, Adnan Menderes Universitesi Tp Fakültesi, Aydn, Turkey 09100²

Received 29 August 2005/ Returned for modification 27 October 2005/ Accepted 20 December 2005

This study investigated the presence of telithromycin and azithromycin efflux in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [³H]telithromycin and [N-methyl-³H]azithromycin in the presence and absence of carbonyl m-chlorophenylhydrazone (CCCP), a protonophore. In 17 strains for which the telithromycin MICs were 0.06 to 0.5 µg/ml (azithromycin MICs, 0.06 to 0.125 µg/ml; clarithromycin MICs, 0.06 to 2 µg/ml), telithromycin and azithromycin accumulations were high without CCCP and not affected by its addition, which indicates absence of efflux. In 22 strains for which the telithromycin MICs were 0.25 to 4 µg/ml (azithromycin MICs, 0.25 to 1 µg/ml; clarithromycin MICs, 1 to 8 µg/ml), initially low levels of telithromycin accumulation became higher after addition of CCCP, indicating a functioning efflux pump. Nineteen strains for which the telithromycin MICs were 2 µg/ml had efflux as well as various mutations in ribosomal proteins L4, L22, and/or 23S rRNA (domains II and V). Of these 19 strains, the telithromycin MICs (8 µg/ml) for 17 of them were significantly raised (azithromycin, MICs 4 to >32 µg/ml; clarithromycin MICs, 8 to >32 µg/ml). From these results we conclude that telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the telithromycin MICs were very low.

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* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu.

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Antimicrobial Agents and Chemotherapy, March 2006, p. 893-898, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.893-898.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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