Tornheim J A, Intini E, Gupta A, Udwadia Z F
Center for Clinical Global Health Education, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Respiratory Medicine, A. Gemelli University Hospital, Catholic University of the Sacred Heart, Rome, Italy.
J Clin Tuberc Other Mycobact Dis. 2020 Jul 24;20:100175. doi: 10.1016/j.jctube.2020.100175. eCollection 2020 Aug.
Multidrug-resistant tuberculosis (MDR-TB) is an increasing problem worldwide, and 24% occurs in India. Linezolid is associated with improved MDR-TB treatment outcomes but causes significant side-effects and drug susceptibility testing (DST) is rarely available. This study assessed whether clinical factors could predict linezolid resistance.
An observational cohort of adults and adolescents with MDR-TB at a tertiary care hospital in Mumbai, India was analyzed for clinical, laboratory, and radiographic findings associated with linezolid resistance.
In total, 343 MDR-TB patients had linezolid DST performed, and 23 (6.7%) had linezolid-resistant MDR-TB. Univariable analysis associated linezolid resistance with underweight (odds ratio (OR)-1.07, 95% confidence interval (CI):1.01-1.12); number of previous providers (OR:1.03, 95% CI:1.00-1.05); previous treatment with linezolid (OR:1.12, 95% CI:1.06-1.05), bedaquiline (OR:1.55, 95% CI:1.22-1.98), or clofazimine (OR:1.08 95% CI:1.03-1.16); cavitary disease (OR:1.10, 95% CI:1.04-1.16) and percent lung involvement (OR:1.02, 95% CI:1.01-1.03) on radiograph. DST associated linezolid resistance with resistance to fluoroquinolones (OR:1.08, 95% CI:1.01-1.14), injectables (OR:1.09, 95% CI:1.03-1.15), ethionamide (OR:1.09, 95% CI:1.03-1.15), and PAS (OR:1.13, 95% CI:1.06-1.21). In multivariate analysis, only prior linezolid and percent lung involvement were associated with linezolid resistance.
To maximize treatment benefits while minimizing toxicity, DST remains an important tool to identify linezolid resistance.
耐多药结核病（MDR-TB）在全球范围内是一个日益严重的问题，其中24%发生在印度。利奈唑胺与改善耐多药结核病治疗结果相关，但会引起严重副作用，且很少有药物敏感性试验（DST）。本研究评估了临床因素是否可预测利奈唑胺耐药性。
对印度孟买一家三级护理医院的成年和青少年耐多药结核病观察队列进行分析，以确定与利奈唑胺耐药性相关的临床、实验室和影像学检查结果。
共有343例耐多药结核病患者进行了利奈唑胺DST，其中23例（6.7%）为耐利奈唑胺的耐多药结核病。单变量分析显示，利奈唑胺耐药性与体重不足（比值比（OR）-1.07，95%置信区间（CI）：1.01-1.12）、既往治疗医生数量（OR：1.03，95%CI：1.00-1.05）、既往使用利奈唑胺治疗（OR：1.12，95%CI：1.06-1.05）、贝达喹啉（OR：1.55，95%CI：1.22-1.98）或氯法齐明（OR：1.08，95%CI：1.03-1.16）、空洞性疾病（OR：1.10，95%CI：1.04-1.16）以及胸部X线片上的肺部受累百分比（OR：1.02，95%CI：1.01-1.03）有关。DST显示，利奈唑胺耐药性与对氟喹诺酮类药物（OR：1.08，95%CI：1.01-1.14）、注射用药物（OR：1.09，95%CI：1.03-1.15）、乙硫异烟胺（OR：1.09，95%CI：1.03-1.15）和对氨基水杨酸（OR：1.13，95%CI：1.06-1.21）的耐药性有关。多变量分析显示，只有既往使用利奈唑胺和肺部受累百分比与利奈唑胺耐药性有关。
为了在使毒性最小化的同时最大化治疗益处，DST仍然是识别利奈唑胺耐药性的重要工具。
