Division of Infectious Diseases.
J Infect Dis. 2014 Jun 1;209(11):1754-63. doi: 10.1093/infdis/jiu040. Epub 2014 Jan 16.
Patients with multidrug-resistant (MDR) tuberculosis may have phenotypic heterogeneity in results of drug-susceptibility tests (DSTs). However, the impact of this on clinical outcomes among patients treated for MDR tuberculosis is unknown.
Phenotypic DST heterogeneity was defined as presence of at least 1 Mycobacterium tuberculosis isolate susceptible to rifampicin and isoniazid recovered <3 months after MDR tuberculosis treatment initiation from a patient with previous documented tuberculosis due to M. tuberculosis resistant to at least rifampicin and isoniazid. The primary outcome was defined as good (ie, cure or treatment completion) or poor (ie, treatment failure, treatment default, or death). A secondary outcome was time to culture conversion. Cox proportional hazard models were used to determine the association between phenotypic DST heterogeneity and outcomes.
Phenotypic DST heterogeneity was identified in 33 of 475 patients (7%) with MDR tuberculosis. Poor outcome occurred in 126 patients (28%). Overall, patients with MDR tuberculosis who had phenotypic DST heterogeneity were at greater risk of poor outcome than those with MDR tuberculosis but no phenotypic DST heterogeneity (adjusted hazard ratio [aHR], 2.1; 95% confidence interval [CI], 1.2-3.6). Among HIV-infected patients with MDR tuberculosis, the adjusted hazard for a poor outcome for those with phenotypic DST heterogeneity was 2.4 (95% CI, 1.3-4.2) times that for those without phenotypic DST heterogeneity, whereas among HIV-negative patients with MDR tuberculosis, the adjusted hazard for those with phenotypic DST heterogeneity was 1.5 (95% CI, .5-4.3) times that for those without phenotypic DST heterogeneity. HIV-infected patients with MDR tuberculosis with phenotypic DST heterogeneity also had a longer time to culture conversion than with HIV-infected patients with MDR tuberculosis without phenotypic DST heterogeneity (aHR, 2.9; 95% CI, 1.4-6.0).
Phenotypic DST heterogeneity among persons with HIV infection who are being treated for MDR tuberculosis is associated with poor outcomes and longer times to culture conversion.
耐多药结核病（MDR-TB）患者的药敏试验（DST）结果可能存在表型异质性。然而，这对 MDR-TB 治疗患者的临床结局的影响尚不清楚。
表型 DST 异质性定义为在 MDR-TB 治疗开始后 <3 个月，从先前有记录的耐至少利福平异烟肼的结核分枝杆菌导致的结核病患者中，至少分离出 1 株对利福平异烟肼敏感的结核分枝杆菌分离株。主要结局定义为良好（即治愈或治疗完成）或不良（即治疗失败、治疗中断或死亡）。次要结局是培养转换时间。使用 Cox 比例风险模型来确定表型 DST 异质性与结局之间的关联。
在 475 例 MDR-TB 患者中，有 33 例（7%）存在表型 DST 异质性。126 例患者（28%）发生不良结局。总体而言，与无表型 DST 异质性的 MDR-TB 患者相比，表型 DST 异质性的 MDR-TB 患者不良结局的风险更高（调整后的危险比[aHR]，2.1；95%置信区间[CI]，1.2-3.6）。在 HIV 感染的 MDR-TB 患者中，表型 DST 异质性患者不良结局的调整后的危险比为无表型 DST 异质性患者的 2.4 倍（95%CI，1.3-4.2），而在 HIV 阴性的 MDR-TB 患者中，表型 DST 异质性患者的调整后的危险比为无表型 DST 异质性患者的 1.5 倍（95%CI，0.5-4.3）。表型 DST 异质性的 HIV 感染的 MDR-TB 患者的培养转换时间也长于无表型 DST 异质性的 HIV 感染的 MDR-TB 患者（aHR，2.9；95%CI，1.4-6.0）。
在接受 MDR-TB 治疗的 HIV 感染者中，表型 DST 异质性与不良结局和培养转换时间延长相关。
