title: Emergence of resistance to rifampin and rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis.
abstract: 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.
authors.affiliation: Department of Pediatrics, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 49, Brooklyn, NY 11203, USA. kutlin@downstate.edu
authors.forename: Andrei
authors.initials: A
authors.lastname: Kutlin
authors.forename: Stephan
authors.initials: S
authors.lastname: Kohlhoff
authors.forename: Patricia
authors.initials: P
authors.lastname: Roblin
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hammerschlag
authors.forename: Paul
authors.initials: P
authors.lastname: Riska
mesh_terms: D001483:Base Sequence; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000235:genetics; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*
chemical_list: D012294:Rifamycins; C068980:KRM 1648; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin
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