title: Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41).
abstract: OBJECTIVE
  Antibiotic therapy of pulmonary Mycobacterium abscessus infection is based on a combination treatment including clarithromycin. Recent data demonstrated that M. abscessus may carry a chromosomal, inducible erm gene coding for the ribosomal methylase Erm(41). The purpose of this study was to investigate whether in patients with chronic M. abscessus infection undergoing clarithromycin therapy, M. abscessus acquires clarithromycin resistance mutations in the rrl gene in addition to the presence of an inducible Erm(41) methylase.
  
  
  METHODS
  We determined clarithromycin MICs, erm(41) and rrl sequences for 29 clinical M. abscessus subsp. abscessus isolates of five different patients. The isolates were obtained between 2007 and 2011 covering a longitudinal observation period of 2-4 years for the individual patients.
  
  
  RESULTS
  In three out of five patients with an initial rrl wild-type isolate, follow-up isolates demonstrated acquisition of resistance mutations in the rrl gene in addition to the presence of an inducible Erm methylase.
  
  
  CONCLUSIONS
  Our results show that in M. abscessus, clarithromycin resistance mutations in the 23S rRNA peptidyltransferase region provide an additional selective advantage independent of a functional erm(41) gene.
authors: Institut für Medizinische Mikrobiologie, Nationales Zentrum für Mykobakterien, Universität Zürich, 8006 Zürich, Switzerland. florian.maurer@imm.uzh.ch
authors: Florian P
authors: FP
authors: Maurer
authors: Vera
authors: V
authors: Rüegger
authors: Claudia
authors: C
authors: Ritter
authors: Guido V
authors: GV
authors: Bloemberg
authors: Erik C
authors: EC
authors: Böttger
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D020459:Genes, rRNA; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009161:Mycobacterium / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy / Q000382:microbiology; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017291:Clarithromycin