Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41)
Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm(41)
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DOI：
10.1093/jac/dks279
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发表时间：
2012-11-01
影响因子：
5.2
通讯作者：
Boettger, Erik C.
中科院分区：
文献类型：
--
作者：
Maurer, Florian P.;Rueegger, Vera;Boettger, Erik C.
肺部脓肿分枝杆菌感染的抗生素治疗是基于包括克拉霉素在内的联合治疗。最近的数据表明，脓肿分枝杆菌可能携带一个染色体上可诱导的erm基因，编码核糖体甲基酶Erm(41)。本研究的目的是调查在接受克拉霉素治疗的慢性脓肿分支杆菌感染患者中，脓肿分支杆菌除了存在可诱导的Erm(41)甲基酶外，是否还获得克拉霉素耐药突变的RRL基因。五种不同患者的脓肿分离株。这些分离株是在2007年至2011年期间获得的，每个患者的纵向观察期为24年。在最初的RRL野生型分离株的5名患者中，有3名患者的后续分离株显示，除了存在可诱导的Erm甲基酶外，还获得了RRL基因的耐药性突变。我们的结果表明，在脓肿分枝杆菌中，克拉霉素耐药突变在23S rRNA肽转移酶区域提供了独立于erm(41)基因的额外选择优势。
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.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 24 years for the individual patients.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.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.