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

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Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41). / Maurer, Florian P; Rüegger, Vera; Ritter, Claudia; Bloemberg, Guido V; Böttger, Erik C.

In: J ANTIMICROB CHEMOTH, Vol. 67, No. 11, 11.2012, p. 2606-11.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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@article{2d7385c4bdfe40b5811edb00be44e110,
title = "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.",
keywords = "Anti-Bacterial Agents, Clarithromycin, DNA, Bacterial, Drug Resistance, Bacterial, Genes, rRNA, Humans, Microbial Sensitivity Tests, Mutation, Mycobacterium, Mycobacterium Infections, Nontuberculous, Sequence Analysis, DNA, Journal Article, Research Support, Non-U.S. Gov't",
author = "Maurer, {Florian P} and Vera R{\"u}egger and Claudia Ritter and Bloemberg, {Guido V} and B{\"o}ttger, {Erik C}",
year = "2012",
month = nov,
doi = "10.1093/jac/dks279",
language = "English",
volume = "67",
pages = "2606--11",
journal = "J ANTIMICROB CHEMOTH",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41)

AU - Maurer, Florian P

AU - Rüegger, Vera

AU - Ritter, Claudia

AU - Bloemberg, Guido V

AU - Böttger, Erik C

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

KW - Anti-Bacterial Agents

KW - Clarithromycin

KW - DNA, Bacterial

KW - Drug Resistance, Bacterial

KW - Genes, rRNA

KW - Humans

KW - Microbial Sensitivity Tests

KW - Mutation

KW - Mycobacterium

KW - Mycobacterium Infections, Nontuberculous

KW - Sequence Analysis, DNA

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/jac/dks279

DO - 10.1093/jac/dks279

M3 - SCORING: Journal article

C2 - 22833642

VL - 67

SP - 2606

EP - 2611

JO - J ANTIMICROB CHEMOTH

JF - J ANTIMICROB CHEMOTH

SN - 0305-7453

IS - 11

ER -