Abstract：
The multidrug resistance of nontuberculous mycobacteria (NTM) poses a significant therapeutic challenge. Rapid and reliable drug susceptibility testing is urgently needed for evidence-based treatment decision, especially for macrolides. This study evaluated the utility of nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (NMTMS) in detecting clarithromycin resistance. Sixty-four clinical isolates were identified to species by NMTMS, and mutations associated with clarithromycin resistance were detected. Twenty-three M. abscessus (MAB) isolates and 30 M. intracellulare isolates (including M. intracellulare alone and M. intracellulare in combination with other SGM species) were included for analysis. The predictive sensitivity of NMTMS in detecting clarithromycin resistance was 82.35% (95% CI, 56.57% to 96.20%), with an AUC of 0.89 (95% CI, 0.77 to 0.96) in all MAB and M. intracellulare (n = 53), and up to 93.33% (95% CI, 68.05% to 99.83%) in MAB alone (n = 23). The assay provides a rapid, high-throughput, and highly sensitive tool for detecting clarithromycin resistance in NTM, especially in MAB. Optimization of the panel is necessary to enhance diagnostic accuracy.
摘要：
非结核分枝杆菌（NTM）的多药耐药性提出了重大的治疗挑战。基于证据的治疗决策迫切需要快速可靠的药敏试验。尤其是大环内酯类。这项研究评估了核苷酸基质辅助激光解吸/电离飞行时间质谱（NMTMS）在检测克拉霉素耐药性中的实用性。通过NMTMS鉴定了64种临床分离株，并检测到与克拉霉素耐药相关的突变。包括23个脓肿分枝杆菌(MAB)分离株和30个胞内分枝杆菌分离株(包括单独的胞内分枝杆菌和与其他SGM物种组合的胞内分枝杆菌)用于分析。NMTMS检测克拉霉素耐药的预测灵敏度为82.35%(95%CI,56.57%~96.20%),所有MAB和细胞内分枝杆菌（n=53）的AUC为0.89（95％CI，0.77至0.96），单用MAB高达93.33%(95%CI，68.05%至99.83%)(n=23)。该测定法提供了一种快速，高通量，和用于检测NTM中克拉霉素耐药性的高灵敏度工具，尤其是MAB。面板的优化对于提高诊断准确性是必要的。
