Department of Bacteriology and Immunology, Beijing Chest Hospitalgrid.414341.7, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou District, Beijing, People's Republic of China.
Department of Laboratory Medicine, The Eighth Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang, People's Republic of China.
Microbiol Spectr. 2022 Jun 29;10(3):e0057422. doi: 10.1128/spectrum.00574-22. Epub 2022 May 31.
The emergence of Mycobacterium abscessus complex (MABC) infection is the most noteworthy health care problem. Clarithromycin (CLA) and amikacin (AMK) constitute the cornerstone of treatment for patients infected with MABC; thus, early detection of resistance to these two drugs is essential for formulating effective therapeutic regimens. In the present study, we aimed to validate the use of MeltPro MAB assay, a melting curve analysis with dually labeled probes, on a set of clinical isolates to detect CLA and AMK resistance. A total of 103 clinical MABC strains were collected in our analysis, including 76 strains of M. abscessus . (MAA) and 27 strains of M. abscessus (MAM). susceptibility testing revealed that two isolates exhibited intrinsic CLA resistance by harboring A2270T mutation in , and inducible resistance was noted in 42 isolates. Additionally, two MAA isolates with erm(41)T28 genotype were susceptible to CLA. Notably, we found three out of 44 isolates had two melting curve peaks, representing the simultaneous presence of mutant and the wild type in these specimens. In contrast, no known mutations were identified in six AMK-resistant isolates. Further analysis revealed that MeltPro yielded 100% and 96.67% sensitivity and specificity for detecting CLA resistance. In summary, this study firstly demonstrates that MeltPro is a promising diagnostic for early detection of CLA resistance for MABC isolates, which significantly improves the turnaround time within 2 h. Approximate two fifths of MABC isolates are resistant to CLA by 23S rRNA mutation or its methylation, emphasizing the urgent need for early detection of CLA resistance prior to empirical treatment of MABC infections. Mycobacterium abscessus complex (MABC) has attracted increasing attention due to the numerous cases of infection. This pathogen is notorious for its intrinsic drug resistance, which complicates clinical management of patients with MABC infections. Clarithromycin (CLA) and amikacin (AMK) are the cornerstone of treatment regimens for MABC. Herein, our data firstly demonstrates that MeltPro is a promising diagnostic for early detection of CLA resistance for MABC isolates. The high frequency of CLA-resistant MABC isolates in China emphasizes the urgent need for early detection of CLA resistance prior to empirical treatment of MABC infections.
分支杆菌脓肿复合体（MABC）感染的出现是最值得关注的医疗保健问题。克拉霉素（CLA）和阿米卡星（AMK）构成了治疗感染 MABC 的患者的基石；因此，早期检测对这两种药物的耐药性对于制定有效的治疗方案至关重要。在本研究中，我们旨在通过熔解曲线分析带有双重标记探针的 MeltPro MAB 测定法验证其在一组临床分离株中检测 CLA 和 AMK 耐药性的应用。我们的分析共收集了 103 株临床 MABC 菌株，包括 76 株脓肿分枝杆菌（MAA）和 27 株脓肿分枝杆菌（MAM）。药敏试验显示，两个分离株由于在 23S rRNA 上存在 A2270T 突变而表现出内在的 CLA 耐药性，并且在 42 个分离株中观察到诱导性耐药性。此外，两个具有 erm(41)T28 基因型的 MAA 分离株对 CLA 敏感。值得注意的是，我们发现 44 个分离株中有 3 个具有两个熔解曲线峰，代表这些标本中同时存在突变体和野生型。相比之下，在 6 个 AMK 耐药分离株中未发现已知突变。进一步分析表明，MeltPro 检测 CLA 耐药性的敏感性和特异性均为 100%和 96.67%。总之，本研究首次表明，MeltPro 是一种有前途的诊断方法，可用于早期检测 MABC 分离株的 CLA 耐药性，将周转时间缩短至 2 小时内。约五分之二的 MABC 分离株通过 23S rRNA 突变或其甲基化对 CLA 耐药，这强调了在经验性治疗 MABC 感染之前急需早期检测 CLA 耐药性。分支杆菌脓肿复合体（MABC）由于感染病例众多而受到越来越多的关注。该病原体因其固有耐药性而臭名昭著，这增加了临床管理 MABC 感染患者的难度。克拉霉素（CLA）和阿米卡星（AMK）是治疗 MABC 的基石。在此，我们的数据首次表明，MeltPro 是一种有前途的诊断方法，可用于早期检测 MABC 分离株的 CLA 耐药性。中国 CLA 耐药 MABC 分离株的高频率强调了在经验性治疗 MABC 感染之前急需早期检测 CLA 耐药性。
