Risk Factors for Poor Treatment Outcomes in Patients with MDR-TB and XDR-TB in China: Retrospective Multi-Center Investigation

Background

The treatment of patients with MDR- and XDR-TB is usually more complex, toxic and costly and less effective than treatment of other forms of TB. However, there is little information available on risk factors for poor outcomes in patients with MDR- and XDR-TB in China.

Methodology/Principal Findings

We retrospectively analyzed the clinical records of HIV-negative TB Patients with culture-proven MDR- or XDR-TB who were registered from July 2006 to June 2011 at five large-scale Tuberculosis Specialized Hospitals in China. Among 1662 HIV-seronegative TB cases which were culture-positive for M. tuberculosis complex and had positive sputum-smear microscopy results, 965 cases (58.1%) were DR-TB, and 586 cases (35.3%) were classified as having MDR-TB, accounting for 60.7% of DR-TB. 169 cases (10.2%) were XDR-TB, accounting for 17.5% of DR-TB, 28.8% of MDR-TB. The MDR-TB patients were divided into XDR-TB group (n=169) and other MDR-TB group (non-XDR MDR-TB) (n=417). In total, 240 patients (40.95%) had treatment success, and 346 (59.05%) had poor treatment outcomes. The treatment success rate in other MDR-TB group was 52.2%, significantly higher than that in the XDR-TB group (13%, P<0.001). In multivariate logistic regression analysis, poor outcomes were associated with duration of previous anti-TB treatment of more than one year (OR, 0.077; 95% CI, 0.011-0.499, P<0.001), a BMI less than 18.5 kg/m² (OR, 2.185; 95% CI, 1.372-3.478, P<0.001), XDR (OR, 13.368; 95% CI, 6.745-26.497, P<0.001), retreatment (OR, 0.171; 95% CI, 0.093-0.314, P<0.001), diabetes (OR, 0.305; 95% CI, 0.140-0.663, P=0.003), tumor (OR, 0.095; 95% CI, 0.011-0.795, P=0.03), decreased albumin (OR, 0.181; 95% CI, 0.118-0.295, P<0.001), cavitation (OR, 0.175; 95% CI, 0.108-0.286, P<0.001).

Conclusions/Significance

The patients with MDR-TB and XDR-TB have poor treatment outcomes in China.The presence of extensive drug resistance, low BMI, hypoalbuminemia, comorbidity, cavitary disease and previous anti-TB treatment are independent prognostic factors for poor outcome in patients with MDR-TB.     

Clinical Benefit of Delamanid (OPC-67683) in the Treatment of Multidrug-Resistant Tuberculosis Patients in China

The cure rates are much lower for multidrug-resistant (MDR) tuberculosis (TB) patients. Delamanid (OPC-67683) has been evaluated in phase-II MDR-TB clinical trials. Herein, we reviewed MDR-TB cases in which treatment regimens, with/without delamanid, were administered. Thirty-eight patients were enrolled; 26 received delamanid-containing regimens (treatment group) while 12 received placebo-containing regimens (control group) for 56 days. Data regarding clinical/radio-microbiological characteristics, drug tolerability, and treatment outcomes were collected. We found that all patients had isolates resistant to a median of 5 (range 2–7) drugs; 24 (92.3 %) patients in treatment group and 11 (91.7 %) in control group had cavities. Culture conversion was obtained in 32 pulmonary TB cases (median 74.5 days). At data censure, 30/38 patients successfully completed therapy with documented negative cultures for at least 18 months before the end of treatment. Two patients (5 consecutive negative cultures) are still on treatment. Six patients had poor outcome (3 failures/2 lost/1 death). In 13 patients, adverse events were observed that included mental disorder, QT interval prolongation, and increased blood cortisol whereas only 3 patients stopped delamanid treatment because of adverse events. It was, therefore, concluded that delamanid was well-tolerated, had low rates of discontinuation, and could be effective for treating MDR-TB.     

杉木人工林土壤真菌遗传多样性

为探明杉木人工林土壤真菌遗传多样性及其与环境因子的关系,采用454测序技术对土壤真菌的遗传多样性进行了分析,测定了黄丰桥林场杉木人工林土壤真菌的遗传多样性与环境因子的相关性。试验结果表明:①不同代数、林龄的杉木人工林土壤理化性质及林下植被多样性均有显著差异。第1代杉木幼林林土壤肥力较高,有机质、全N、速效K的均值分别为88.02g/kg、2.56 g/kg、84.96 mg/kg均高于第2代和第3代杉木幼林林,速效N和含水量的均值分别为22.86 mg/kg和26.28%低于其他样地。杉木幼林林下植被多样性最为丰富。②通过454测序技术分析发现第1代杉木幼林真菌Ace丰富度指数、Chao丰富度指数及群落遗传多样性指数均大于第2代杉木幼林和第3代杉木幼林。杉木人工林土壤中粪壳菌纲(Sordariomycetes)真菌为优势种群。不同栽培代数杉木人工林的真菌群落存在差异,其中块菌科(Tuberaceae)为第2代和第3代杉木林特有真菌,而不同发育阶段的杉木人工林的真菌群落差异不明显。③经RDA分析,杉木人工林土壤主要真菌群落受含水量、有机质、速效P、速效K影响较大。土壤真菌群落遗传多样性Shannon-Wiener多样性指数与林下植被多样性、土壤全N显著正相关,土壤真菌Chao指数与土壤真菌Shannon-Wiener多样性指数、土壤全N含量显著正相关。本研究表明不同栽培代数杉木人工林的真菌群落存在差异,土壤真菌群落与环境因子之间具有相关性。     

Increased Cytokines Response in Patients with Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease

Objectives

To explore the change and its significance of cytokines in patients with pulmonary tuberculosis complicated with COPD.

Methods

The immune function of 152 cases of pulmonary tuberculosis with COPD was detected to compare with 150 cases of patients with pulmonary tuberculosis, 157 cases of patients with COPD and 50 cases of healthy volunteers who were in the hospital during the same period. T lymphocyte cell population in peripheral blood was detected by flow cytometry. The serum levels of sIL-2R, IL-6, IFN-γ, TNF-α were measured using ELISA.

Results

The percentage of CD4+ T cells in TB patients with or without COPD and COPD patients without TB was significantly lower than that in control group. The percentage of CD4+ T cells in patients with TB and COPD was significantly lower than that in the non-COPD TB patients. The percentage of CD8+ T cells was higher in the TB patients group than that in control group. The CD4+/CD8+ ratio in the TB patients group was significantly lower than that in control group. The concentrations of sIL-2R, IL-6, TNF-α, IFN-γ in TB patients with or without COPD and COPD patients without TB were significantly higher than those in control group. In addition, sIL-2R, IL-6, TNF-α concentrations in the patients with TB and COPD were higher than those in the non-COPD TB patients. The concentrations of sIL-2R, IL-6, TNF-α, IFN-γ in COPD patients with TB were significantly higher than those in COPD patients without TB. There was a significant negative correlation between serum levels of TNF-α, IL-6 and FEV1 (%, predicted) in COPD without TB group.

Conclusions

The patients with pulmonary tuberculosis complicated with COPD were impaired in cellular immunity, and its extent of immune impairment is more serious than those of the patients with pulmonary tuberculosis and the patients with COPD.