Abstract
BackgroundLimited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Relevant data about mortality of XDR-TB patients in literature are limited and likely underestimate the real situation in China, since the majority of patients with XDR-TB are lost to follow-up after discharge from TB hospitals. In this study, we sought to investigate the mortality and associated risk factors of Human Immunodeficiency Virus (HIV)-negative patients with XDR-TB in China.MethodsAll patients who were diagnosed with XDR-TB for the first time in four TB care centers across China between March 2013 and February 2015 were consecutively enrolled. Active tracking through contacting patients or family members by phone or home visit was conducted to obtain patients’ survival information by February 2017. Multivariable Cox regression models were used to evaluate factors associated with mortality.ResultsAmong 67 patients enrolled, the mean age was 48.7 (Standard Deviation [SD] = 16.7) years, and 51 (76%) were men. Fourteen patients (21%) were treatment naïve at diagnosis indicating primary transmission. 58 (86.8%) patients remained positive for sputum smear or culture when discharged. During a median follow-up period of 32 months, 20 deaths occurred, with an overall mortality of 128 per 1000 person-years. Among patients who were dead, the median survival was 5.4 months (interquartile range [IQR]: 2.2–17.8). Seventeen (85%) of them died at home, among whom the median interval from discharge to death was 8.4 months (IQR: 2.0–18.2). In Cox proportional hazards regression models, body mass index (BMI) < 18.5 kg/m2 (adjusted hazard ratio [aHR] = 4.5, 95% confidence interval [CI]: 1.3–15.7), smoking (aHR = 4.7, 95%CI:1.7–13.2), or a clinically significant comorbidity including heart, lung, liver, or renal disorders or auto-immune diseases (aHR = 3.5, 95%CI: 1.3–9.4), were factors independently associated with increased mortality.ConclusionOur study suggested an alarming situation of XDR-TB patients in China with a sizable proportion of newly transmitted cases, a high mortality rate, and a long period in community. This observation calls for urgent actions to improve XDR-TB case management in China, including providing regimens with high chances of cure and palliative care, and enhanced infection control measures.
Highlights
Limited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide
Outcomes of Extensive drug-resistant (XDR)-TB patients Among the 67 patients, 3 patients died during hospitalization, 6 patients discharged from the hospital while sputum smear/culture converted to negative, and 58 (86.8%) patients remained positive for sputum smear or culture when discharged
In patients who died during the tracked period, the median survival was only 5.4 (IQR: 2.2–17.8) months; three of them died in the hospital, 17 (85%) died at home, Seventeen (85%) of them died at home, among whom the median interval from discharge to death was 8.4 months (IQR: 2.0–18.2) and the median time from discharge to death was 8.4 (IQR: 2.0–18.2) months
Summary
Limited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Tuberculosis (TB) is one of the top 10 causes of human death [1]. Based on 2017 Global Tuberculosis Report [1], more than 100 countries reported cases of XDR-TB in 2016, the rate of treatment success of XDR-TB were reported merely 30% in 2014. 89 territories and countries had started using bedaquiline and 54 had used delamanid by June 2017 to improve outcomes for Multi-drug resistant tuberculosis (MDR-TB) /XDR-TB, the mortality of XDR-TB reported from treatment cohorts were still above 30% [1,2,3,4,5]. The high treatment-associated costs are unsustainable in the middle-income and low-income countries that account for over 95% of tuberculosis related deaths [6]. The “transmitted resistance”-XDR-TB has well described and confirmed throughout the world [7, 8]
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