Background About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. Methods A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. Results A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups ( P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ 2 = 6.077, P = 0.014). There was no statistically significant difference ( P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) ( P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups ( P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) ( P = 0.754). Conclusion The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It’s urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.

Objective: To assess the efficacy of different antibiotics combined on Mycobacterium abscessus subspecies abscessus pulmonary disease（M.abscessus-PD） and analyze the influencing factors of treatment outcomes for 6 months. Methods: Sixty-six patients in Beijing Chest Hospital, Capital Medical University diagnosed with M.abscessus-PD were enro1led prospectively from January 1st, 2016 to October 1st, 2022. Clinical information of the patients were collected, including gender, age, body mass index, clinical manifestations, history of past illness and anti-tuberculosis treatment, imaging examinations, laboratory examinations and medications. The factors influencing treatment outcomes of M.abscessus-PD for 6 months among different therapicregimens was compared. Results: After 6 months of treatment, 32（48.5%） achieved sputum culture conversion and 34（51.5%） didn’t among the 66 patients. The result shows that the 6-month sputum culture conversion rate of azithromycin users（57.4%, 27/47） was higher than clarithromycin users（26.3%, 5/19）, with statistically significant（χ~2=5.250,P=0.022）. In 24 cases（36.4%, 24/66） treated with imipenem, 17（70.8%, 17/24） achieved 6 months sputum culture conversion, which was higher than that of non-imipenem（35.7%, 15/42）, with statistically significant difference（χ~2=7.542, P=0.006）. The efficacy of multidrug therapy regimen showed that macrolide combined with amikacin, imipenem, linezolid and clofazimine achieved 68.4%（13/19） culture conversion rate after 6 months. Multivariate analysis shows that patients treated with macrolide combined with imipenem were more likely to achieve sputum culture conversion within 6 months（OR（95%CI）=0.229（0.077-0.676））. Conclusion: In the initial stage of treatment, at least 4 weeks of injection use（amikacin and imipenem）, and the combination of macrolides with amikacin, clofazimine, and linezolid in the continued treatment, may have good curative effect on M.abscessus-PD.

Objective: To understand the characteristics of nontuberculous mycobacteria（NTM） pulmonary disease, and provide evidence for clinical diagnosis and treatment of NTM pulmonary disease. Methods: The clinical data of 93 patients with NTM pulmonary disease admitted to Beijing Chest Hospital affiliated to Capital Medical University between January 2018 and December 2019 were analyzed retrospectively. Treatment effectivenesses were compared for different treatment. Results: Among 93 patients with NTM pulmonary disease, there were 49 cases infected with Mycobacterium intracellular, 28 cases with Mycobacterium abscesses, 4 cases with Mycobacterium avium, 4 cases with Mycobacterium kansasii, 3 cases with Mycobacterium xenopi, 2 case co-infected with Mycobacterium abscesses and Mycobacterium intracellular, one case with Mycobacterium gordonii, Mycobacterium fortuitum or Mycobacterium stutzeri each. 61 patients（65.59%） had received antituberculosis treatment before the diagnosis of NTM pulmonary disease. 90（96.77%） patients had complications, of which 52（57.78%） patients had bronchiectasis, followed by 12（13.33%） patients with chronic obstructive pulmonary disease（COPD）. 83 cases（89.25%） received anti-NTM treatment, and 47 cases（56.63%） completed the course of treatment among whom the success rate of the treatment of pulmonary disease with Mycobacterium avium complex was 51.85%（14/27） while the treatment success rate of Mycobacterium abscesses pulmonary disease was 76.92%（10/13）. 48 cases（57.83%） had adverse drug reactions of different degrees during the treatment, and 15 cases（18.07%） discontinued the treatment. 16 patients（19.28%） were lost to follow-up. Conclusion: Mycobacterium intracellular lung disease is the most common NTM pulmonary disease. Most patients were complicated with bronchiectasis, COPD and other basic lung diseases. The clinical characteristics of NTM pulmonary disease and pulmonary tuberculosis are similar, which are easily misdiagnosed as pulmonary tuberculosis. The cure rate of NTM pulmonary disease is low, and the rate of treatment interruption and loss to follow-up is high.

目的:分析复治肺结核治疗新方案(简称"新方案")与复治标准方案(简称"标准化方案")治疗首次复治敏感肺结核的有效性及安全性.方法:采用多中心前瞻性队列研究方法,选取2019年1月至2021年12月期间在中国14个省及3个直辖市中的24家结核病定点医疗机构住院确诊的592例首次复治肺结核患者(包括敏感、单耐药、多耐药及部分菌阴复治肺结核),将患者随机纳入新方案组[4H-L2-E-Z-Lfx/4H-L2-E;H:异烟肼(体质量＜50 kg,0.3 g/d;体质量 ≥50 kg,0.4～0.5 g/d),L:利福喷丁(0.6 g/次,2 次/周),E:乙胺丁醇(体质量＜50 kg,0.75 g/d;体质量≥50 kg,0.75～1.0 g/d),Z:吡嗪酰胺(1.5 g/d),Lfx:左氧氟沙星(0.5～0.6 g/d)]和标准化方案组(3H-R-E-Z/6H-R-E,常规剂量;R:利福平).本研究参照纳排标准选取其中首次复治敏感肺结核患者(均为涂阳培阳)为研究对象,比较新方案组患者和标准化方案组的治疗成功率、失败率、不良反应发生率等,以评估新方案在复治敏感肺结核患者中的有效性及安全性.结果:共纳入首次复治敏感肺结核患者238例,其中新方案组172例(72.3％),标准化方案组66例(27.7％).新方案组治疗成功率[77.3％(133/172)]高于标准化方案组[62.1％(41/66)],治疗失败率[4.7％(8/172)]低于标准化方案组[27.3％(18/66)],差异均有统计学意义(x2=5.609,P=0.018;x2=25.083,P=0.000),但两组患者不良反应发生率[4.7％(8/172)和3.0％(2/66)]差异无统计学意义(Fisher精确概率法,P=0.731).结论:新方案可提高首次复治敏感肺结核的治疗成功率及降低治疗失败率,总体治疗效果及安全性均较好.

Background and objective Retreatment pulmonary tuberculosis (PTB) still accounts for a large proportion of tuberculosis, and the treatment outcome is unfavorable. The recurrence of retreatment PTB based on long-term follow-up has not been well demonstrated. This study aimed to evaluate effect of a modified regimen on drug-sensitive retreated pulmonary tuberculosis. Methods This multicenter cohort study was conducted in 29 hospitals from 23 regions of China from July 1, 2009, to December 31, 2020. Patients were divided into two treatment regimen groups including experimental group [modified regimen (4H-Rt2-E-Z-S(Lfx)/4H-Rt2-E)]and control group [standard regimen (2H-R-E-Z-S/6H-R-E or 3H-R-E-Z/6H-R-E)]. The patients enrolled were followed up of 56 months after successful treatment. We compared the treatment success rate, treatment failure rate, adverse reaction rate, and recurrence rate between two regimens. Multivariate Cox regression model was used to identify the potential risk factors for recurrence after successful treatment with proportional hazards assumptions tested for all variables. Results A total of 381 patients with retreatment PTB were enrolled, including 244 (64.0%) in the experimental group and 137 (36.0%) in the control group. Overall, the treatment success rate was significant higher in the experimental group than control group (84.0 vs. 74.5%, P = 0.024); no difference was observed in adverse reactions between the two groups (25.8 vs. 21.2%, P > 0.05). A total of 307 patients completed the 56 months of follow-up, including 205 with the modified regimen and 102 with the standard regimen. Among these, 10 cases (3.3%) relapsed, including 3 in the experimental group and 7 in the control group (1.5% vs 6.9%, P = 0.035). Reduced risks of recurrence were observed in patients treated with the modified regimen compared with the standard regimen, and the adjusted hazard ratio was 0.19 (0.04–0.77). Conclusion The modified retreatment regimen had more favorable treatment effects, including higher treatment success rate and lower recurrence rate in patients with retreated drug-sensitive PTB.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis(Mtb), continues to be an important global health problem. Hence, gaining a comprehensive understanding of the immune characteristics in TB could aid the improvement of vaccines and therapeutics for TB, especially for severe TB.Methods: Single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing were applied to dissect the peripheral immune responses of active TB and reveal the molecular mechanisms of TB pathogenesis. Single-cell transcriptional profiles were obtained from 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases) and integrated with 2 published profiles of latent TB infection.Findings: We observed a decrease in multiple peripheral immune cells (e.g., NKs, DCs and MAIT), and an increase in monocytes and megakaryocytes in TB patients, particularly with severe disease. We also discovered a significant increase in monocytes resembling myeloid-derived suppressor cells in severe patients that may be involve in immune paralysis. The immune landscape in severe patients were characterized by widespread immune exhaustion in Th1, CD8+ T and NK cells, high cytotoxic state in CD8+ T and NK cells, and significant activation of cell apoptosis and migration pathways in T and NK cells. Systemic upregulation of pro-inflammatory cytokines and inflammatory response genes, mainly by monocytes, and similarly increased pro-inflammatory cytokine concentrations in the plasma may contribute to the inflammatory cytokine storms previously observed in severe patients.Interpretation: This comprehensive single-cell analysis of peripheral immune landscape will improve the understanding of TB immunopathogenesis, offering potential targets for therapies and vaccines for TB control.Funding Information: This work was supported by grants from National Key Research and Development Program of China (Grant Nos. 2021YFC2301101, 2021YFC2301102), Public service development and reform pilot project of Beijing Medical Research Institute (BMR2019-11), National natural science foundation of China (81970900, 82100011), Beijing Public Health Experts Project (2022-3-040), Beijing Social Science Foundation Project (19GLB033), Key Project of the Department of Science and Technology, Beijing, China (Grant Nos.D181100000418003, Z191100006619078).Declaration of Interests: The lead author and guarantor affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.Ethics Approval Statement: The ethical approval for this study was obtained from the Beijing Chest Hospital ethics committee (ethical approval No. YNLX-2022-006). Written informed consent was acquired from each participant.

目的 评价优化方案治疗复治药物敏感肺结核患者的临床疗效及安全性.方法 采取多中心、随机、开放、平行、对照的前瞻性队列研究,中心单位统一发放随机号随机分组,选取复治涂阳培阳或涂阴培阳肺结核患者共381例为研究对象,其中优化治疗方案组(简称"优化方案组")244例和标准化治疗方案组(简称"标准方案组")137例.采用SPSS 19.0软件进行数据统计,计数资料采用x2检验,当理论频数＜1时,采用Fisher确切概率法检验,以P＜0.05为差异有统计学意义.比较两组方案治疗成功率及不良反应发生等情况.结果 疗程结束,优化方案组治愈175例,完成治疗30例,治疗成功率为84.0％(205/244);标准方案组治愈92例,完成治疗10例,治疗成功率为74.5％(102/137),两组比较差异有统计学意义(x2 =5.128,P=0.024).优化方案组和标准方案组不良反应发生率分别为25.8％(63/244)和21.2％(29/137),两组比较差异无统计学意义(x2 =1.037,P=0.309);严重不良反应发生率分别为2.5％(6/244)和4.4％(6/137),两组差异无统计学意义(x2=0.525,P = 0.469).结论 优化方案可提高复治药物敏感肺结核患者治疗成功率,且不增加药物不良反应的发生率.

目的 探讨复治肺结核合并糖尿病患者的影响因素,为制定肺结核合并糖尿病防治政策提供相关依据.方法 2009年10月-2012年12月选择我国22家结核病定点医疗机构确诊并进行治疗的复治肺结核患者395例进行调查,按照是否合并糖尿病分为单纯复治肺结核组及合并糖尿病组,运用x2检验比较两组患者在社会学特征等方面的差异,运用多因素非条件logistic回归分析肺结核合并糖尿病的危险因素.结果 共纳入395例患者,其中合并糖尿病60例,占15.2％;单纯肺结核患者335例,占84.8％.两组患者在年龄(x2 = 10.459,P= 0.005 3),体质指数(BMI)(x2= 15.070,P= 0.000 5),职业(x2 = 11.620,P = 0.002 9),婚姻状况(x2 = 9.999,P = 0.006 7)差异具有显著性.复治肺结核患者40～59岁年龄组和≥60岁年龄组,BMI＜18.5(kg/m2)及BMI≥24.0(kg/m2),已婚是复治肺结核合并糖尿病的危险因素,OR(95％CI)值分别为2.159(1.050～4.439),5.017(1.485～16.951)、4.946(1.279～8.705)、5.732(1.918～17.133)及4.476(1.248～10.504).结论 复治肺结核合并糖尿病与患者的年龄、体重指数、婚姻状态有关.

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120 minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30 minutes interval and 120 minutes interval were 21.8 ± 2.0 and 19.2 ± 2.0 μg/mL for rifampin, 1.6 ± 0.2 and 2.1 ± 0.2 μg/mL for isoniazid (INH), 1.5 ± 0.1and 1.5 ± 0.2 μg/mL for ethambutol (EMB), and 49.2 ± 3.7 and 41.5 ± 3.9 μg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ± 0.4 μg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ± 1.0 μg/mL), and slow acetylator (2.5 ± 1.0 μg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).

糖尿病(diabetes mellitus,DM)患者逐年增加.2017年全球估算有4.25亿人患有糖尿病,预计到2045年糖尿病患者将增至6.29亿人.其中95％为2型DM[1].糖尿病患者是结核病(tuberculosis, TB)的易感人群.全球结核病患者中,约15％患者合并DM,其中40％的病例来自印度和中国 [2].目前中国是世界上糖尿病患者最多的国家,2019年中国估算有1.16亿名成年人患有糖尿病.DM增加了结核病患病风险,甚至更高.我国是全球结核病高负担国家之一,耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)和利福平耐药结核病(rifampicin-resistant tuberculosis,RR-TB)的疫情非常严重.WHO报告 [3],2018年全球RR-TB新发病例48.4万,其中MDR-TB约37万例,而其治疗成功率仅为56％,死亡率达15％.结核病的持续存在与糖尿病的急剧增加,导致双重疾病共患(TB-DM)人数逐年增加,对人类健康造成重大威胁,成为消灭结核病的一大障碍,急需应对两病并存的策略. 糖尿病(diabetes mellitus,DM)患者逐年增加.2017年全球估算有4.25亿人患有糖尿病,预计到2045年糖尿病患者将增至6.29亿人.其中95％为2型DM[1].糖尿病患者是结核病(tuberculosis, TB)的易感人群.全球结核病患者中,约15％患者合并DM,其中40％的病例来自印度和中国 [2].目前中国是世界上糖尿病患者最多的国家,2019年中国估算有1.16亿名成年人患有糖尿病.DM增加了结核病患病风险,甚至更高.我国是全球结核病高负担国家之一,耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)和利福平耐药结核病(rifampicin-resistant tuberculosis,RR-TB)的疫情非常严重.WHO报告 [3],2018年全球RR-TB新发病例48.4万,其中MDR-TB约37万例,而其治疗成功率仅为56％,死亡率达15％.结核病的持续存在与糖尿病的急剧增加,导致双重疾病共患(TB-DM)人数逐年增加,对人类健康造成重大威胁,成为消灭结核病的一大障碍,急需应对两病并存的策略.

Objective Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. Methods A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

Tuberculosis (TB) patient serum cytokine levels may be predictive of anti-tuberculosis treatment progress. Here, serum levels of cytokines TNF-α, IL-4, sIL-2R and IFN-γ were measured then correlated to clinical TB manifestations, bacterial burden, chest imaging findings and clinical course. Study subjects included 67 newly diagnosed pulmonary TB (PTB) patients with active disease admitted to Beijing Chest Hospital for anti-TB chemotherapeutic treatment. Blood was drawn at 0 months (pre-treatment), 1–2 months (at any time between 1 and 2 month) and after 6 months completion of treatment and serum TNF-α, IL-4, sIL-2R and IFN-γ levels were measured in duplicate using enzyme-linked immunosorbent assays (ELISAs). Correlation analysis was conducted to evaluate sensitivity and specificity of cytokine levels as predictors of disease activity and treatment progress. The results indicated that the pre-treatment serum TNF-α level of the smear-negative group was lower than that of the smear 1+ group, while serum TNF-α after 6 months completion of treatment and IFN-γ levels at 1–2 months and after 6 months completion of treatment were significantly lower, respectively, than at 0 months (before treatment) (P < 0.05). Using a cut-off value of 845 pg/ml, serum TNF-α level was predictive of treatment progress, with a sensitivity of 51%, specificity of 60% and AUC of 0.594 (P = 0.013). Meanwhile, using a cut-off value of 393 pg/ml, serum IFN-γ provided superior monitoring efficacy, with a sensitivity of 60%, specificity of 64% and AUC of 0.651 (P = 0.017). In conclusion, both serum TNF-α and IFN-γ levels might be useful biomarkers for monitoring treatment progress.

目的 评估糖尿病对肺结核患者治疗反应的影响.方法 选择首都医科大学附属北京胸科医院2012年1月至2014年12月收治的1950例成年肺结核患者,其中于1640例非糖尿病患者中随机抽取126例作为单纯肺结核组,于310例同时患有肺结核和糖尿病的患者中随机抽取126例作为糖尿病合并肺结核组.比较两组患者临床表现和影像学表现以及抗结核治疗期间的细菌学反应的差异,评估两组患者抗结核治疗2个月后痰培养阴转率.结果 两组患者的临床症状相似.与单纯肺结核组比较,糖尿病合并肺结核组患者初始痰抗酸杆菌的涂阳率较高,初次胸片上出现空洞性病变的比例较低(P<0.05).两组患者经积极抗结核治疗2个月后,糖尿病合并肺结核组64例(50.8％)痰培养仍呈阳性,而单纯肺结核组为31例(24.6％).结论 糖尿病合并肺结核患者抗结核治疗2个月后痰培养阴转延迟的比例较高.对糖尿病患者应加强结核病相关症状的健康教育,降低对活动性结核病的评估阈值,密切监测糖尿病合并肺结核患者痰菌阴转情况.

目的 探讨复治菌阳肺结核治疗成功后再次复发患者的相关危险因素.方法 采取多中心、随机、开放、平行、对照的前瞻性队列研究,联合国内22家结核病防治机构共同参与.对复治肺结核满疗程治疗成功后的300例患者,在2013年3月至2019年1月进行了近6年的随访,共发现有23例治疗成功后的肺结核患者再次复发(复发组),治疗成功后有277例未复发者(未复发组).对两组在既往(初治时和复治时)累计用药时间、此次治疗前是否存在耐药、此次复治方案、此次治疗时服用利福平或利福喷丁(简称“利福类药物”)剂量,以及治疗成功时胸片显示的空洞情况进行分析,探讨其治疗成功后再次复发的危险因素.统计方法采用SPSS 19.0软件进行数据的统计学分析,计数资料采用x2检验或Fisher确切概率法;两组患者的临床指标与复发间的关系采用logistic回归分析,以P＜0.05为差异有统计学意义.结果 复发组胸片显示空洞闭合率[7.1％(1/14)]明显低于未复发组[49.2％(90/183)],差异具有统计学意义(x2=9.246,P=0.002).单因素分析复发与未复发两组在既往(此次治疗前)累计使用一线抗结核药物时间≥7个月者分别为60.9％(14/23)和29.1％(80/275),差异具有统计学意义(x2=9.926,P=0.002).在此次治疗前药物敏感性试验结果存在耐药者复发组占63.6％ (14/22),与未复发组[35.8％ (93/260)]比较,差异也具有统计学意义(x2=6.690,P=0.010).多因素分析既往累计用药时间和此次复治前是否存在耐药与再次复发有相关性,OR值(95％CI值)分别为4.911(1.885～12.792)和3.085 (1.204～7.902)(P=0.001和P=0.019);另外发现此次复治方案中使用低剂量利福类药物对再次复发有影响,OR值(95％CI值)为3.499(1.302～9.404)(P=0.013).结论 既往累计抗结核用药时间≥7个月、此次复治前存在耐药、此次复治方案中使用低剂量利福类药物,以及治疗结束时胸片仍显示有空洞者是复治肺结核再次复发的危险因素.

Background Our aim was to assess whether the use of cycloserine (CS) would bring additional benefit for multidrug-resistant tuberculosis (MDR-TB) patients, and to estimate the incidence and associated risk factors of adverse drug reactions (ADRs) from CS. Patients and methods In this study, we retrospectively reviewed the clinical outcomes and ADRs of MDR-TB patients treated with CS containing regimens between January 2012 and June 2015 in China. Results A total of 623 MDR-TB cases enrolled in this study received regimens containing CS. Of these cases, in 411 of the patients 374 (66.0%) were “cured” and 37 (5.9%) “complete treatment” by the end of the study. The elderly, patients with prolonged previous exposure to and history of anti-TB drugs, and pre-existing co-morbidity were more likely to be associated with adverse outcomes of MDR-TB patients (P<0.05). Hyperuricemia (22.8%, 142/623) was the most frequently observed ADR among these cases, while the most noted ADRs associated with the administration of CS was psychiatric symptoms, accounting for 4.3% (27/623) of study population. Nineteen (70.4%) out of 27 cases with psychiatric symptoms occurred before the 6-month timepoint, and were notably, the highest proportion of serious adverse, 29.6% (8/27) of which were noted after discontinuation of CS. Conclusion Our study demonstrates that a CS-containing regimen achieved a highly successful outcome in the treatment of MDR-TB and promising tolerance in Chinese population. The potential emergence of serious psychiatric symptoms highlights that patients need to be closely monitored for these conditions during treatment that includes CS.

AbstractMoxifloxacin (MFX) showed good activityin vitroagainstMycobacterium abscessus(M. abscessus) and was suggested as one of the antibiotic regimens for adults withM. abscessusdisease. However, some other studies showed that MFX showed less or none activity againstM. abscessus. In our study we aim to evaluate MFX activity againstM. abscessususing zebrafish (ZF) modelin vivo. MIC of each drugs were determined by broth microdilution method.M. abscessuslabeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activityin vitro. Butin vivoMFX showed limited restriction toM. abscessus. The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy onMycobacterium abscessus in vivousing ZF model. MFX’s activityin vivoneed to be confirmed.

Moxifloxacin (MFX) showed good activity against () and was suggested as one of the antibiotic regimens for adults with disease. However, some other studies showed that MFX showed less or none activity against . In our study we aim to evaluate MFX activity against using zebrafish (ZF) model . MIC of each drugs were determined by broth microdilution method. labeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activity . But MFX showed limited restriction to . The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy on using ZF model. MFX’s activity need to be confirmed.

目的 分析含环丝氨酸(Cs)化疗方案治疗耐多药肺结核患者发生药物不良反应的情况.方法 选取2013年1月至2016年6月全国11家单位纳入全球基金第五轮耐多药结核病防治项目、符合选例标准的耐多药肺结核患者作为研究对象,共计623例.所有患者均采用标准化治疗方案,即:6PZA-Am(Cm)-Lfx(Mfx)-Pto-Cs/18PZA-Lfx(Mfx)-Pto-Cs;替代方案:PAS替代Pto,Cm替代Am,Mfx替代Lfx(PZA:吡嗪酰胺;Am:阿米卡星;Cm:卷曲霉素;Lfx:左氧氟沙星;Mfx:莫西沙星;Pto:丙硫异烟胺;Cs:环丝氨酸;PAS:对氨基水杨酸钠).收集患者在治疗过程中的药物不良反应发生情况,分析药物不良反应的临床特征、严重程度、发生时间、持续时间、处理方法及预后,并判定其与药物之间的相关性.结果 623例研究对象中有316例(50.7％)发生至少一种药物不良反应,36例(5.8％)患者由于药物不良反应停服药物或者更改治疗方案.最常见的药物不良反应为高尿酸血症(22.8％,142/623)和肝功能异常(18.8％,117/623);出现与Cs很可能相关的中枢神经系统或精神症状者有27例(4.3％),发生时间的中位数(四分位数)[M(Q1,Q3)]为3(2,6)个月,对患者进行停用Cs或心理辅导等处理后,症状消失.结论 应用含Cs的标准化疗方案进行治疗的耐多药肺结核患者中,发生中枢神经系统或精神症状与Cs有关,在对患者使用含Cs方案治疗期间需密切监测其中枢神经系统或精神系统症状.

We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.