Mixed Mycobacterium tuberculosis-Strain Infections Are Associated With Poor Treatment Outcomes Among Patients With Newly Diagnosed Tuberculosis, Independent of Pretreatment Heteroresistance
Mixed Mycobacterium tuberculosis-Strain Infections Are Associated With Poor Treatment Outcomes Among Patients With Newly Diagnosed Tuberculosis, Independent of Pretreatment Heteroresistance
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DOI：
10.1093/infdis/jiy480
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发表时间：
2018-12-15
影响因子：
6.4
通讯作者：
Zetola, Nicola M.
中科院分区：
文献类型：
--
作者：
Shin, Sanghyuk S.;Modongo, Chawangwa;Zetola, Nicola M.
背景。异抗性结核分枝杆菌感染（定义为耐药菌株和药物敏感菌株的同时感染）可以解释在混合菌株结核分枝杆菌感染的患者中观察到的结核病治疗结果不佳的风险较高。我们在博茨瓦纳开始一线结核病治疗的结核病患者人群样本中研究了混合菌株感染的临床效果，同时控制了治疗前的异质耐药性。方法。我们对基线原代培养分离株进行了 24 位分枝杆菌散布重复单位变量串联重复分析和靶向深度测序，以分别检测混合感染和异质耐药性。药物敏感型、微观异型耐药、宏观异型耐药和固定耐药感染被定义为在inhA启动子、katG基因和rpoB基因的耐药赋予结构域中耐药频率分别= 95%的感染。 结果。在该研究纳入的 260 名结核病患者中，25 名（9.6%）患有混合感染，30 名（11.5%）治疗结果不佳。异烟肼存在微观异抗性、宏观异抗性和固定耐药性，其中异烟肼分别为 11 例（4.2%）、2 例（0.8%）和 11 例（4.2%），利福平分别为 21 例（8.1%）、0 例（0%）和 10 例（3.8%）。在多变量分析中，混合感染而非异质耐药感染独立预测不良治疗结果。结论。在博茨瓦纳开始一线结核病治疗的患者中，混合感染与结核病治疗结果不佳相关，与异质耐药性无关。
Background. Heteroresistant Mycobacterium tuberculosis infections (defined as concomitant infection with drug-resistant and drug-susceptible strains) may explain the higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections while controlling for pretreatment heteroresistance in a population-based sample of patients with tuberculosis starting first-line tuberculosis therapy in Botswana.Methods. We performed 24-locus mycobacterial interspersed repetitive unit-variable number tandem-repeat analysis and targeted deep sequencing on baseline primary cultured isolates to detect mixed infections and heteroresistance, respectively. Drug-sensitive, micro-heteroresistant, macro-heteroresistant, and fixed-resistant infections were defined as infections in which the frequency of resistance was = 95%, respectively, in resistance-conferring domains of the inhA promoter, the katG gene, and the rpoB gene.Results. Of the 260 patients with tuberculosis included in the study, 25 (9.6%) had mixed infections and 30 (11.5%) had poor treatment outcomes. Micro-heteroresistance, macro-heteroresistance, and fixed resistance were found among 11 (4.2%), 2 (0.8%), and 11 (4.2%), respectively, for isoniazid and 21 (8.1%), 0 (0%), and 10 (3.8%), respectively, for rifampicin. In multivariable analysis, mixed infections but not heteroresistant infections independently predicted poor treatment outcomes.Conclusions. Among patients starting first-line tuberculosis therapy in Botswana, mixed infections were associated with poor tuberculosis treatment outcomes, independent of heteroresistance.