Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Department of Internal Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
Lancet. 2014 Apr 5;383(9924):1230-9. doi: 10.1016/S0140-6736(13)62675-6. Epub 2014 Jan 17.
Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps.
Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing.
All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16-26·04). Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6-26·4). Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003).
In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment.
European and Developing Countries Clinical Trials Partnership, South African National Research Foundation (SARChI), and the South African Medical Research Council.
广泛耐药结核病（XDR）患者的长期治疗相关结局尚不清楚。我们对一组患者进行了随访，以解决知识空白。
2008 年 3 月至 2012 年 8 月，我们前瞻性地随访了来自南非三个省的 107 例患者，这些患者在 2002 年 8 月至 2008 年 2 月期间被诊断为 XDR 结核病。从 56 例患者中获得的可利用分离株进行了基因分型，以建立菌株类型并进行扩展药敏试验。
所有患者均接受了住院经验性治疗，中位数使用了 8 种药物（IQR 6-10）。44 例（41%）患者 HIV 阳性。56 株分离株中有 36 株（64%）至少对 8 种药物耐药，耐药药物种类越多与北京基因型相关（p=0·01）。在 24 个月的随访中，17 例（16%）患者结局良好（即治疗治愈或完成），49 例（46%）死亡，7 例（7%）失访（连续中断治疗至少 2 个月），25 例（23%）治疗失败。在 60 个月时，12 例（11%）患者结局良好，78 例（73%）死亡，4 例（4%）失访，11 例（10%）治疗失败。45 例患者出院，其中 26 例（58%）实现了痰培养转阴，19 例（42%）治疗失败。出院后治疗失败患者的中位生存时间为 19.84 个月（IQR 4.16-26.04）。基因分型方法显示，治疗失败并出院的患者及其家庭中存在病例聚类和传播。22 例（21%）患者实现了净痰培养转阴，净痰培养转阴的中位时间为 8.7 个月（IQR 5.6-26.4）。净痰培养转阴的独立预测因素为无耐多药结核病史（p=0·0007）和使用氯法齐明（p=0·0069）。总生存的独立预测因素为净痰培养转阴（p<0·0001）和氯法齐明治疗（p=0·021）。在 HIV 患者中，抗逆转录病毒治疗也是生存的预测因素（p=0·003）。
在南非，广泛耐药结核病患者的长期结局较差，无论 HIV 状况如何。由于适当的长期住院或姑息治疗设施稀缺，大量治疗失败且痰培养阳性的广泛耐药结核病患者已从医院出院，很可能将疾病传播到更广泛的社区。迫切需要测试新的联合方案，政策制定者应实施干预措施，以尽量减少治疗失败患者传播疾病的风险。
欧洲和发展中国家临床试验合作组织、南非国家研究基金会（SARChI）和南非医学研究理事会。
