Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.
Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.
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DOI：
10.1097/qai.0000000000000650
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发表时间：
2015-08-15
期刊：
影响因子：
--
通讯作者：
Padayatchi N
中科院分区：
文献类型：
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作者：
OʼDonnell MR;Pillay M;Pillay M;Werner L;Master I;Wolf A;Mathema B;Coovadia YM;Mlisana K;Horsburgh CR;Padayatchi N
卷曲霉素是治疗广泛耐药结核病（XDR-TB）的关键抗分枝杆菌药物。在南非，对新诊断的广泛耐药结核病没有常规进行卷曲霉素药敏试验。本研究旨在评估南非夸祖鲁-纳塔尔地区新诊断的广泛耐药结核病患者卷曲霉素耐药的患病率、临床意义和分子流行病学。对结核病转诊医院收治的既往未接受过广泛耐药结核治疗的连续广泛耐药结核患者进行的回顾性队列研究。一个子集的分离株进行了扩展DST（包括卷曲霉素），突变分析和IS 6110限制性片段长度多态性（RFLP）测定。确定了216名符合条件的广泛耐药结核患者。大多数接受卷曲霉素治疗（72%），为年轻（中位年龄35.5岁）和女性（56%）。165人（76%）为艾滋病毒阳性，109人（66%）正在接受抗逆转录病毒治疗。52例患者的亚组进行了完整的DST。47/52例（90.4%）广泛耐药结核患者对卷曲霉素耐药。卷曲霉素耐药患者的死亡率和培养转化率比卷曲霉素敏感患者更差，但差异无统计学意义。rrs基因A1401 G突变与卷曲霉素耐药相关。卷曲霉素耐药菌株以F15/LAM 4/KZN谱系为主（80%），且常见聚集性（92.5%）。卷曲霉素耐药性在夸祖鲁-纳塔尔的广泛耐药结核病患者中很常见，主要是由于一种高度耐药菌株正在全省范围内传播，并与高死亡率有关。卷曲霉素应包括在所有广泛耐药结核患者的常规DST中。不包括注射剂的新药物治疗方案应作为广泛耐药结核的经验性治疗进行操作试验。
Capreomycin is a key antimycobacterial drug in treatment of extensively drug-resistant tuberculosis (XDR-TB). Drug susceptibility testing (DST) for capreomycin is not routinely performed in newly diagnosed XDR-TB in South Africa. We performed this study to assess the prevalence, clinical significance, and molecular epidemiology of capreomycin resistance in newly diagnosed XDR-TB patients in KwaZulu-Natal, South Africa. Retrospective cohort study of consecutive XDR-TB patients admitted to a TB referral hospital without prior XDR-TB treatment. A subset of isolates had extended DST (including capreomycin), mutational analysis and IS6110 restriction fragment length polymorphism (RFLP) assays. 216 eligible XDR-TB patients were identified. The majority were treated with capreomycin (72%), were young (median age 35.5) and female (56%). 165 (76%) were HIV+, and 109 (66%) were on antiretroviral therapy. A subset of 52 patients had full DST. 47/52 (90.4%) XDR-TB patients were capreomycin resistant. Capreomycin-resistant patients experienced worse mortality and culture conversion than capreomycin susceptible though this difference was not statistically significant. The A1401G mutation in the rrs gene was associated with capreomycin resistance. The majority of capreomycin resistant strains were F15/LAM4/KZN lineage (80%), and clustering was common in these isolates (92.5%). Capreomycin resistance is common in patients with XDR-TB in KwaZulu-Natal, is predominantly due to ongoing province-wide transmission of a highly resistant strain, and is associated with high mortality. Capreomycin should be included in routine DST in all XDR-TB patients. New drug regimens that do not include injectable agents should be operationally tested as empiric treatment in XDR-TB.