Rockwood Neesha, Wojno Justyna, Ghebrekristos Yonas, Nicol Mark P, Meintjes Graeme, Wilkinson Robert J
Department of Medicine, Imperial College, London, United Kingdom
Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
J Clin Microbiol. 2017 May;55(5):1508-1515. doi: 10.1128/JCM.00025-17. Epub 2017 Mar 1.
The utility of a line probe assay (Genotype MTBDR) performed directly on 2-month sputa to monitor tuberculosis treatment response is unknown. We assessed if direct testing of 2-month sputa with MTBDR can predict 2-month culture conversion and long-term treatment outcome. Xpert MTB/RIF-confirmed rifampin-susceptible tuberculosis cases were recruited at tuberculosis diagnosis and followed up at 2 and 5 to 6 months. MTBDR was performed directly on 2-month sputa and on all positive cultured isolates at 2 and 5 to 6 months. We also investigated the association of a positive direct MTBDR at 2 months with subsequent unsuccessful tuberculosis treatment outcome (failure/death during treatment or subsequent disease recurrence). A total of 279 patients (62% of whom were HIV-1 coinfected) were recruited. Direct MTBDR at 2 months had a sensitivity of 78% (95% confidence interval [CI], 65 to 87) and specificity of 80% (95% CI, 74 to 84) to predict culture positivity at 2 months with a high negative predictive value of 93% (95% CI, 89 to 96). Inconclusive genotypic susceptibility results for both rifampin and isoniazid were seen in 26% of MTBDR tests performed directly on sputum. Compared to a reference of MTBDR performed on positive cultures, the false-positive resistance rate for direct testing of MTBDR on sputa was 4% for rifampin and 2% for isoniazid. While a positive 2-month smear was not significantly associated with an unsuccessful treatment outcome (adjusted odds ratio [aOR], 2.69; 95% CI, 0.88 to 8.21), a positive direct MTBDR at 2 months was associated with an unsuccessful outcome (aOR 2.87; 95% CI, 1.11 to 7.42). There is moderate utility of direct 2-month MTBDR to predict culture conversion at 2 months and also to predict an unfavorable outcome.
直接对2个月的痰液进行线性探针分析（Genotype MTBDR）以监测结核病治疗反应的效用尚不清楚。我们评估了使用MTBDR直接检测2个月的痰液是否可以预测2个月的培养转化和长期治疗结果。在结核病诊断时招募Xpert MTB/RIF确诊的利福平敏感结核病病例，并在2个月和5至6个月时进行随访。MTBDR直接对2个月的痰液以及2个月和5至6个月时所有阳性培养分离株进行检测。我们还研究了2个月时直接MTBDR阳性与随后结核病治疗结果不佳（治疗期间失败/死亡或随后疾病复发）之间的关联。共招募了279名患者（其中62%合并感染HIV-1）。2个月时直接MTBDR预测2个月时培养阳性的敏感性为78%（95%置信区间[CI]，65至87），特异性为80%（95%CI，74至84），阴性预测值较高，为93%（95%CI，89至96）。直接对痰液进行的MTBDR检测中，26%的利福平和异烟肼基因易感性结果不确定。与对阳性培养物进行MTBDR检测的参考结果相比，直接对痰液进行MTBDR检测的利福平假阳性耐药率为4%，异烟肼为2%。虽然2个月时涂片阳性与治疗结果不佳无显著关联（调整优势比[aOR]，2.69；95%CI，0.88至8.21），但2个月时直接MTBDR阳性与治疗结果不佳相关（aOR 2.87；95%CI，1.11至7.42）。直接进行2个月的MTBDR对预测2个月时的培养转化以及预测不良结果具有中等效用。
