Brown-Elliott Barbara A, Vasireddy Sruthi, Vasireddy Ravikiran, Iakhiaeva Elena, Howard Susan T, Nash Kevin, Parodi Nicholas, Strong Anita, Gee Martha, Smith Terry, Wallace Richard J
Mycobacteria/Nocardia Laboratory, University of Texas Health Science Center at Tyler, Tyler, Texas, USA
Mycobacteria/Nocardia Laboratory, University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
J Clin Microbiol. 2015 Apr;53(4):1211-5. doi: 10.1128/JCM.02950-14. Epub 2015 Feb 4.
The erm(41) gene confers inducible macrolide resistance in Mycobacterium abscessus subsp. abscessus, calling into question the usefulness of macrolides for treating M. abscessus subsp. abscessus infections. With an extended incubation (14 days), isolates with MICs of ≥8 μg/ml are considered macrolide resistant by current CLSI guidelines. Our goals were to determine the incidence of macrolide susceptibility in U.S. isolates, the validity of currently accepted MIC breakpoints, and the erm(41) sequences associated with susceptibility. Of 349 isolates (excluding those with 23S rRNA gene mutations), 85 (24%) had clarithromycin MICs of ≤8 μg/ml. Sequencing of the erm(41) genes from these isolates, as well as from isolates with MICs of ≥16 μg/ml, including ATCC 19977T, revealed 10 sequevars. The sequence in ATCC 19977T was designated sequevar (type) 1; most macrolide-resistant isolates were of this type. Seven sequevars contained isolates with MICs of >16 μg/ml. The T28C substitution in erm(41), previously associated with macrolide susceptibility, was identified in 62 isolates (18%) comprising three sequevars, with MICs of ≤2 (80%), 4 (10%), and 8 (10%) μg/ml. No other nucleotide substitution was associated with macrolide susceptibility. We recommend that clarithromycin susceptibility breakpoints for M. abscessus subsp. abscessus be changed from ≤2 to ≤4 μg/ml and that isolates with an MIC of 8 μg/ml have repeat MIC testing or erm sequencing performed. Our studies suggest that macrolides are useful for treating approximately 20% of U.S. isolates of M. abscessus subsp. abscessus. Sequencing of the erm gene of M. abscessus subsp. abscessus will predict inducible macrolide susceptibility.
erm(41)基因可使脓肿分枝杆菌脓肿亚种产生诱导型大环内酯类耐药性，这使得大环内酯类药物在治疗脓肿分枝杆菌脓肿亚种感染方面的有效性受到质疑。按照当前美国临床和实验室标准协会（CLSI）指南，经过延长培养（14天）后，最低抑菌浓度（MIC）≥8μg/ml的分离株被视为大环内酯类耐药。我们的目标是确定美国分离株中大环内酯类药物敏感性的发生率、当前公认的MIC断点的有效性以及与敏感性相关的erm(41)序列。在349株分离株（不包括那些23S rRNA基因突变的分离株）中，85株（24%）的克拉霉素MIC≤8μg/ml。对这些分离株以及MIC≥16μg/ml的分离株（包括ATCC 19977T）的erm(41)基因进行测序，发现了10个序列变体。ATCC 19977T中的序列被指定为序列变体（类型）1；大多数大环内酯类耐药分离株属于这种类型。7个序列变体包含MIC>16μg/ml的分离株。在62株（18%）分离株中鉴定出erm(41)基因中的T28C替换，这些分离株包含三个序列变体，MIC分别为≤2μg/ml（80%）、4μg/ml（10%）和8μg/ml（10%）。没有其他核苷酸替换与大环内酯类药物敏感性相关。我们建议将脓肿分枝杆菌脓肿亚种的克拉霉素敏感性断点从≤2μg/ml改为≤4μg/ml，并且MIC为8μg/ml的分离株应进行重复MIC检测或erm基因测序。我们的研究表明，大环内酯类药物可用于治疗约20%的美国脓肿分枝杆菌脓肿亚种分离株。对脓肿分枝杆菌脓肿亚种的erm基因进行测序将预测诱导型大环内酯类药物敏感性。
