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Antimicrobial Agents and Chemotherapy, March 2005, p. 903-907, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.903-907.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Emergence of Resistance to Rifampin and Rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis

Departments of Pediatrics,¹ Medicine, SUNY Downstate Medical Center, Brooklyn, New York²

Received 26 May 2004/ Returned for modification 15 September 2004/ Accepted 18 November 2004

Although rifamycins have excellent activity against Chlamydophila pneumoniae and Chlamydia trachomatis in vitro, concerns about the possible development of resistance during therapy have discouraged their use for treatment of chlamydial infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is the most active antimicrobial against C. pneumoniae and C. trachomatis in vitro, indicating its potential for treatment of acute and chronic C. pneumoniae and C. trachomatis infections. We investigated the effect of serial passage of two C. pneumoniae isolates and two serotypes of C. trachomatis in subinhibitory concentrations of rifalazil and rifampin on the development of phenotypic and genotypic resistance. C. trachomatis developed resistance to both antimicrobials within six passages, with higher level resistance to rifampin (128 to 256 µg/ml) and lower level resistance to rifalazil (0.5 to 1 µg/ml). C. pneumoniae TW-183 developed only low-level resistance to rifampin (0.25 µg/ml) and rifalazil (0.016 µg/ml) after 12 passages. C. pneumoniae CWL-029 failed to develop resistance to either drug. Two unique mutations emerged in the rpoB gene of rifampin (L456I) and rifalazil (D461E)-resistant C. pneumoniae TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil-resistant C. trachomatis UW-3/Cx/D, and a unique mutation (V136F) was found in rifalazil-resistant BU-434/L₂. No mutations were detected in the entire rpoB gene of rifampin-resistant BU-434/L₂. This is the first description of antibiotic resistance-associated mutations in C. pneumoniae and of rifampin resistance in C. trachomatis not associated with mutations in the rpoB gene.

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