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关于脓肿分枝杆菌亚种和erm41序列变异体的抗生素敏感性测试和耐药基因分型的标准化解读

Standardized interpretation of antibiotic susceptibility testing and resistance genotyping for Mycobacterium abscessus with regard to subspecies and erm41 sequevar.

作者信息

Mougari Faiza, Amarsy Rishma, Veziris Nicolas, Bastian Sylvaine, Brossier Florence, Berçot Béatrice, Raskine Laurent, Cambau Emmanuelle

机构信息

National Reference Center for Mycobacteria and Antimycobacterial Resistance, Paris, France APHP, Hôpital Lariboisière, Laboratory of Bacteriology, Paris, France Univ Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, France.

APHP, Hôpital Lariboisière, Laboratory of Bacteriology, Paris, France Univ Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, France.

出版信息

J Antimicrob Chemother. 2016 Aug;71(8):2208-12. doi: 10.1093/jac/dkw130. Epub 2016 May 4.

Abstract

OBJECTIVES

The objective of this study was to provide standardized antibiotic susceptibility testing (AST) for Mycobacterium abscessus with regard to subspecies.

METHODS

One hundred and sixty-five clinical isolates were tested for susceptibility to 15 antibiotics using a commercial microdilution method, at two reading times: (i) early reading time (ERT), when the growth control was first positive; and (ii) late reading time (LRT), of 14 days, for detecting inducible resistance. In addition, genes or mutations involved in resistance were studied [erm(41), rrl and rrs].

RESULTS

Three patterns were observed for clarithromycin: (i) MIC >16 mg/L at ERT (median 5 days) for 15 isolates [10 subsp. abscessus erm(41) sequevar T28, 3 subsp. bolletii and 2 subsp. massiliense] among which 9 harboured an a2058g/c rrl mutation; (ii) MIC ≤16 mg/L at ERT, but >16 mg/L at LRT, for 106 isolates [84 abscessus erm(41) T28 and 22 bolletii] showing intrinsic inducible resistance; and (iii) MIC ≤4 mg/L at ERT and LRT for 44 isolates [18 abscessus erm(41) C28 and 26 massiliense]. Amikacin MIC was >64 mg/L for eight isolates [five abscessus erm(41) T28, two massiliense and one bolletii] among which seven harboured the a1408g rrs mutation, but ≤64 mg/L for the remaining isolates without mutation. For the other antibiotics, only one WT pattern was observed, with cefoxitin, tigecycline and linezolid showing MIC values compatible with susceptibility.

CONCLUSIONS

Standard AST can predict clarithromycin and amikacin resistance using interpretation rules with regard to subspecies. For other antibiotics, since only one pattern is observed, there is no need for systematic phenotypic or genotypic testing.

摘要

目的

本研究的目的是针对脓肿分枝杆菌亚种提供标准化的抗生素敏感性试验(AST)。

方法

采用商业微量稀释法,在两个读数时间对165株临床分离株进行15种抗生素的敏感性测试:(i)早期读数时间(ERT),即生长对照首次呈阳性时;(ii)14天的晚期读数时间(LRT),用于检测诱导性耐药。此外,还研究了与耐药相关的基因或突变[erm(41)、rrl和rrs]。

结果

观察到克拉霉素的三种模式:(i)15株分离株在ERT(中位数5天)时MIC>16 mg/L[10株脓肿亚种erm(41)序列变体T28、3株博莱亚种和2株马赛亚种],其中9株存在a2058g/c rrl突变;(ii)106株分离株在ERT时MIC≤16 mg/L,但在LRT时>16 mg/L[84株脓肿亚种erm(41) T28和22株博莱亚种],显示固有诱导性耐药;(iii)44株分离株在ERT和LRT时MIC≤4 mg/L[18株脓肿亚种erm(41) C28和26株马赛亚种]。8株分离株[5株脓肿亚种erm(41) T28、2株马赛亚种和1株博莱亚种]的阿米卡星MIC>64 mg/L,其中7株存在a1408g rrs突变,但其余无突变的分离株MIC≤64 mg/L。对于其他抗生素,仅观察到一种野生型模式,头孢西丁、替加环素和利奈唑胺的MIC值显示与敏感性相符。

结论

标准AST可使用关于亚种的解释规则预测克拉霉素和阿米卡星耐药性。对于其他抗生素,由于仅观察到一种模式,无需进行系统的表型或基因型检测。

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