Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41)

Abstract

Objectives: 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.