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 microg/ml) and lower level resistance to
rifalazil (0.5 to 1 microg/ml). C. pneumoniae TW-183 developed only low-level resistance to
rifampin (0.25 microg/ml) and
rifalazil (0.016 microg/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/L(2). No mutations were detected in the entire rpoB gene of
rifampin-resistant BU-434/L(2). 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.