Linezolid is an important drug for the treatment of drug-resistant tuberculosis (DR-TB). Acquired linezolid resistance threatens treatment efficacy. This study aimed to analyze the risk factors and molecular mechanisms of linezolid-acquired resistance in a clinical cohort. We conducted a retrospective study of 61 patients with DR-TB who failed linezolid-containing regimens (2017–2021). Paired baseline and post-treatment Mycobacterium tuberculosis isolates were subjected to linezolid Minimum inhibitory concentration (MIC) testing (Microplate Alamar Blue Assay) and sequencing of rplC, rrl (23 S rRNA), and rplD. Acquired resistance was defined as a ≥ 4-fold increase in MIC or the presence of new resistance-conferring mutation. Risk factors were analyzed using logistic regression. Acquired linezolid resistance occurred in 31.1

BACKGROUND:Multidrug-resistant and rifampin-resistant tuberculosis (MDR/RR-TB) remains a formidable challenge to global health. While the integration of bedaquiline (BDQ) has revolutionized the therapeutic landscape for MDR/RR-TB, the clinical necessity and safety profile of extending BDQ administration beyond the conventional 24-week regimen - especially in complex or high-risk cohorts - remain insufficiently characterized. METHODS:This multi-centre retrospective cohort study analysed 189 patients with MDR/RR-TB in China between January 2019 and January 2024. Patients were stratified into a standard-duration group (≤6 months) and an extended-duration group (>6 months). Treatment efficacy, cumulative culture conversion rates, and adverse events were comparatively evaluated. Multivariable logistic regression was employed to identify independent predictors of severe Fridericia-corrected QT (QTcF) prolongation (>500 ms). RESULTS:No significant differences were observed in favourable treatment outcomes between the extended and standard groups (86.8% vs. 85.8%; P = 0.845). Culture conversion rates at the end of treatment were comparable (94.7% vs. 92.0%; P = 0.457). Regarding cardiac safety, the incidence of QTcF >500 ms did not differ significantly between the two cohorts (7.9% vs. 10.6%; P = 0.528). Notably, pre-existing cardiac disease was identified as the most potent independent risk factor for severe QTcF prolongation (OR: 9.01; 95% confidence interval: 2.53-32.12; P < 0.001), rather than the duration of BDQ exposure. CONCLUSIONS:Extended BDQ treatment is both efficacious and well-tolerated in patients with MDR/RR-TB. Prolonged exposure does not inherently increase the risk of cardiotoxicity, suggesting that BDQ duration can be personalized based on clinical need, provided that baseline cardiac comorbidities are rigorously managed.

BACKGROUND:Linezolid is essential for drug-resistant tuberculosis (DR-TB) treatment but causes frequent hematological toxicity. We developed a time-dependent nomogram to predict this risk. METHODS:A prospective cohort of 201 patients with DR-TB receiving linezolid (600 mg/day) was enrolled. Blood trough concentration (Cmin) and clinical variables were measured. Multivariable Cox regression identified predictors, with a nomogram constructed to estimate toxicity probability at 1, 3, and 6 months. Model performance was assessed via calibration curves, C-index, and time-dependent area under the curve (AUC). RESULTS:Ninety-six patients (47.8%) developed hematological adverse events (anemia: 26.4%, leukopenia: 14.4%, thrombocytopenia: 7.0%). Five predictors were significant: Cmin > 2.08 mg/L [Hazard Ratio (HR) = 2.87, p < 0.001]; lower baseline white blood cells (HR = 0.84, p = 0.003), hemoglobin (HR = 0.99, p = 0.033), and creatinine clearance rate (HR = 0.99, p = 0.001); and initial treatment (HR = 0.56 vs. retreatment, p = 0.011). The nomogram showed good discrimination (C-index = 0.73) and calibration. Time-dependent AUCs were 0.74 (1-month), 0.79 (3-month), and 0.80 (6-month). Internal validation via bootstrapping (1000×) confirmed robustness. CONCLUSIONS:This nomogram, integrating Cmin with baseline clinical factors, enables early identification of patients with DR-TB at high risk for hematotoxicity and could guide pre-emptive interventions. However, external validation is required to confirm its generalizability before widespread clinical implementation.

Background:This study aimed to evaluate the efficacy and safety of an all-oral short-term regimen for treating multidrug-resistant tuberculosis (MDR-TB). Methods:In this semirandomized, controlled, multicenter clinical study, patients with MDR-TB who were sensitive to fluoroquinolones were assigned to treatment groups at enrollment. Patients were assigned to group C (4-6 months: bedaquiline + linezolid + clofazimine + moxifloxacin + cycloserine; 5 months: clofazimine + moxifloxacin + cycloserine) unless this protocol was unsuitable or unacceptable, in which case they were randomly assigned to group A (4-6 months: isoniazid + ethambutol + pyrazinamide + protionamide + amikacin + clofazimine + moxifloxacin; 5 months: ethambutol + pyrazinamide + clofazimine + moxifloxacin) or group B (4-6 months: isoniazid + ethambutol + pyrazinamide + protionamide + linezolid + clofazimine + moxifloxacin; 5 months: ethambutol + pyrazinamide + clofazimine + moxifloxacin). The primary outcome was the proportion of patients achieving successful outcomes. Results:From September 2020 to June 2023, 397 patients with MDR-TB were screened and 360 were enrolled. Among them, 90.3% of group C achieved good treatment outcomes, as compared with 57.1% in group A (control) and 75.0% in group B. Group C demonstrated higher sputum culture conversion and pulmonary cavity closure rates than group B, with group A showing the lowest rates. The most common adverse events were skin blackening (29.3%) and hyperuricemia (20.6%). Prolonged QT intervals were observed in 39 participants, predominantly in group C (24.3%). Conclusions:The all-oral 9- to 11-month short-term regimen shows promise as a new treatment option for MDR-TB. Incorporating bedaquiline into an orally administered regimen may improve treatment outcomes and reduce relapse rates. Despite certain limitations, these findings provide valuable insights for developing improved treatments for MDR-TB in China.

Tuberculosis (TB) is a contagious disease that threatens human health worldwide. Combination chemotherapy is usually recommended for this disease. Recently, 2 nitroimidazole-based agents, namely, delamanid and pretomanid, have been approved by regulatory agencies. JDB0131 is a novel, structurally optimized third-generation nitroimidazole antituberculosis agent that incorporates the advantages of earlier compounds. This multicenter, prospective, randomized phase 2a trial was conducted to evaluate its efficacy and safety in patients with tuberculosis (NCT06224036). In total, 52 patients with newly diagnosed TB were recruited. JDB0131 was tested in a dose escalation manner (cohort 1: 100 mg bid, cohort 2: 200 mg qd, and cohort 3: 200 mg bid). For comparison, delamanid (100 mg bid) and classic fixed-dose combination (FDC) regimens were included as controls. The primary endpoint was logarithmic changes in the number of colony formation units (CFUs) in the solid media culture of sputum TB (log10 CFU). The early bactericidal activity (EBA) of JDB0131 was better than that of delamanid. During the time interval between days 0 and 14, JDB0131 at a dose of 200 mg bid (cohort 3) showed superior efficacy over delamanid. At the end of drug intervention (day 14), JDB0131 (all 3 dose levels) achieved superior time to positivity (TTP) over delamanid. Ninety-one adverse events (AEs), including no serious AEs, were attributed to JDB0131 in 30 patients. This trial identified a promising new drug for the increasing TB burden worldwide.

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4–59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7–50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2–14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8–18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. Conclusions The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

Background Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated. Methods A total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE). Results The performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851. Conclusion In summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.

Abstract Background To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays. Methods Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. Results Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P < 0.05). PTB diagnostic specificities of the respective assays were 65.38%, 100%, and 80.77%, which corresponded with kappa coefficient (κ) values of 0.14, 0.40, and 0.56, respectively. These results indicate that nanopore sequencing provided superior overall performance as compared to Xpert and MGIT culture assays and provided significantly greater PTB diagnostic accuracy than Xpert and sensitivity comparable to that of the MGIT culture assay. Conclusion Our findings suggest that improved detection of PTB in suspected cases was achieved using nanopore sequencing-based testing of BALF or sputum samples than was achieved using Xpert and MGIT culture-based assays, and nanopore sequencing results alone cannot be used to rule out PTB.

目的:探索肺结核患者血清细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素4(IL-4)、可溶性白细胞介素受体(sIL-2R)和γ-干扰素(IFN-γ)水平对抗结核治疗效果的预测价值.方法:采用前瞻性队列研究方法,参照入组标准纳入2017年12月至2019年6月首都医科大学附属北京胸科医院收治的67例新诊断活动性肺结核患者作为研究对象.使用酶联免疫吸附试验(ELISA)检测患者治疗前、抗结核治疗1～2个月和治疗6个月时外周血血清TNF-α、IL-4、sIL-2R和IFN-γ水平,对显著差异的指标进行受试者工作特征(ROC)曲线分析以确定其最佳临界值,并以此为界值预测肺结核的活动性和治疗进展.结果:治疗1～2个月的sIL-2R水平[14.1(11.2,19.1)pg/ml]、治疗6个月的TNF-α水平[686.6(226.9,1030.5)pg/ml]和治疗1～2个月的IFN-γ水平[357.0(273.4,431.0)pg/ml]均明显低于治疗前[分别为16.7(12.9,23.9)、848.3(345.2,1201.6)、490.0(303.6,607.9)pg/ml],差异均有统计学意义(χ2=15.276,P=0.036;χ2=33.421,P=0.002;χ2=31.111,P=0.000).ROC曲线分析显示:当血清TNF-α水平为845.2 pg/ml时,治疗有效性的曲线下最大面积(AUC)为0.594(P=0.013);当血清IFN-γ水平为393.3 pg/ml时,治疗有效性的AUC为0.651(P=0.017).以最佳临界值为参照标准,发现治疗前血清IFN-γ和TNF-α水平高于其最佳临界值者(阳性者)分别为43例(64.2％)和34例(50.7％),明显高于治疗1～2个月的IFN-γ[14例(20.9％)]和治疗6个月的TNF-α阳性者[19例(28.4％)],差异均有统计学意义(χ2=34.634,P=0.000;χ2=53.181,P=0.013).结论:血清TNF-α和IFN-γ水平作为监测抗结核治疗的生物标志物可能具有一定意义.

目的:评价白细胞介素-2(IL-2)治疗初治药物敏感肺结核的有效性和安全性.方法:采用前瞻性、随机、对照、多中心临床研究方法,自2017年12月至2019年6月,于我国15个省(市)的17个研究中心连续纳入确诊的初治药物敏感肺结核患者作为研究对象,最终纳入1264例.采用计算机生成的随机化序列进行分组,619例被分配到试验组,645例被分配到对照组.试验组中有560例完成方案治疗,对照组中有591例完成方案治疗.试验组采用含IL-2(在治疗疗程的第1个月采取每日5×105 U皮下注射)和异烟肼、利福平、吡嗪酰胺和乙胺丁醇的背景治疗方案;对照组仅采用异烟肼、利福平、吡嗪酰胺和乙胺丁醇治疗方案.对研究对象在6个月治疗过程中及治疗结束后的12个月内均进行包含痰菌培养和影像学评价的治疗有效性评估,以及包含药物不良反应的治疗安全性评估.结果:试验组治疗成功率为99.8％(559/560),对照组为99.3％(587/591),两组间差异无统计学意义(χ2=1.650,P=0.125).试验组有1例(0.2％)出现不良结局(死亡);对照组有4例(0.7％)出现不良结局,无死亡患者,两组间差异无统计学意义(χ2=1.650,P=0.125).治疗2个月时,试验组空洞闭合率为28.4％(60/211),明显高于对照组的18.5％(46/248),差异有统计学意义(χ2=6.276,P=0.001);试验组痰培养阴转率为96.3％(539/560),明显高于对照组的93.2％(551/591),差异有统计学意义(χ2=5.219,P=0.025).治疗疗程结束时,试验组空洞闭合率为61.6％(130/211),对照组为57.3％(142/248),差异无统计学意义(χ2=0.118,P=0.391).在治疗结束后的12个月内,试验组有15例(2.7％)复发,对照组有19例(3.2％)复发,差异无统计学意义(χ2=0.298,P=0.607).除注射部位皮肤硬结外,两组之间的药物不良反应发生情况均无明显差异.试验组注射部位皮肤硬结发生率为14.8％(83/560).试验组和对照组最常见的药物不良反应均为高尿酸血症[发生率分别为23.2％(130/560)和23.3％(138/591)].结论:含IL-2方案辅助治疗初治药物敏感肺结核或可在治疗早期促进患者痰培养阴转和空洞闭合.

ObjectivesLinezolid can significantly impact drug-resistant tuberculosis (DR-TB) patient outcomes. However, the long-term use of this drug for TB treatment has been limited by adverse reactions and uncertainty regarding optimal dosage regimens for balancing drug efficacy and safety across different populations. This study attempted to find the optimal dosing regimen of linezolid in different populations.MethodsA total of 355 blood samples were collected from 126 DR-TB patients. Population pharmacokinetic analysis (using a one-compartment model) and dose simulations were conducted using NONMEM and R software. The ratio between the area under the free drug plasma concentration-time curve to the MIC (fAUC/MIC) of > 119 and trough concentration (Cmin) ≤ 2 mg/L served as efficacy and safety targets, respectively, toward the formulation of optimal dosage regimens based on a ≥ 90% cumulative fraction of response.ResultsBody weight and blood urea nitrogen levels were the most significant covariates of apparent volume, while creatinine clearance and haemoglobin level significantly influenced apparent clearance. The probability of target attainment for different dosage regimens was evaluated via Monte Carlo simulation. For subjects with MICs of 0.125, 0.25 and 0.5 mg/L, specific total daily doses of ≥ 300 mg, ≥ 450 mg and ≥ 900 mg were required to reach the target, respectively. Subjects with body weight ≤ 70 kg and MIC ≥ 1 mg/L received a total 1200 mg daily dose to reach the probability of target attainment target. Notably, single dosing was safer than multiple dosing at the same daily dose. The optimal dosage regimens for subjects with body weight < 50 kg and ≥ 50 kg were 450 mg/d and 600 mg/d (once daily), respectively.ConclusionOptimal dosage regimens for patients weighing < 50 kg and ≥ 50 kg were 450 mg/d and 600 mg/d, respectively. A single dose was safer than multiple doses.

Purpose Evaluation of the efficacy and safety of IL-2 in the treatment of drug-susceptible tuberculosis. Methods First, the cases of diagnosed drug-susceptible tuberculosis were randomized into two groups-the control group that received the background regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, and the experimental group that received the background regimen plus IL-2. The efficacy and safety evaluations were performed throughout the therapy process as well as 12 months after the treatment completion. Results A total of 1151 patients underwent the randomization, among which 539 (96.2%) of the 560 in the experimental group achieved the sputum culture conversion to negative, compared to the 551 (93.2%) of the 591 in the control group, after 2 months of treatment, with significant difference observed between the groups (P = 0.025). Cavity closure after 2 months in the IL-2 (experimental) group was 60/211 (28.4%) compared to 46/248 (18.5%) in the control group, with a significant difference between the groups (P = 0.001). After treatment completion, the proportion of favorable outcomes was 559/560 (99.8%) in the experimental group and 587/591 (99.3%) in the control group, with no significant difference between the groups. Twelve months after treatment completion, relapse occurred in 15/560 (2.6%) in the IL-2 group and 19/591 (3.2%) in the control group, with no significant difference. Conclusion IL-2 may enhance culture conversion and the cavity closure rate in the early treatment phase, although the enhancement may not be significant after treatment completion.

目的 分析目前初复治肺结核的耐药状况.方法 对2018年1—12月首都医科大学附属北京胸科医院结核科住院的310例耐药肺结核患者的药物敏感试验结果进行回顾性分析,与2010年本院160例耐药情况相比较,组间比较采用χ2检验.结果 与2010年相比,2018年利福平耐药结核病在耐药结核病中占比为10.6％(33/310),差异有显著性(P=0.007);复治耐药中利福平耐药结核病的比例明显升高(P=0.004);耐多药结核病患者在复治耐药中的比例明显升高[64.6％(128/198)],广泛耐药结核病患者的比例明显下降[14.6％(29/198)];在复治耐药结核病中89.2％对利福平耐药的结核病患者同时对异烟肼耐药.结论 利福平耐药结核病在耐药结核病中的比例升高,与XperMTB/RIF快速检测方法的广泛应用有关,利于耐多药结核病的早期发现.

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).

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.

目的 评价利奈唑胺治疗耐药结核病的有效性和安全性.方法 选择2015年2月1日至2018年2月9日首都医科大学附属北京胸科医院收治的耐药结核病患者33例,治疗方案为利奈唑胺每天1次,每次600mg,记录利奈唑胺治疗2周时的血药浓度,治疗前、治疗2周及停药6个月的不良反应发生情况及治疗结果 .结果33例患者中治愈26例(78.8％),完成治疗2例(6.1％),治疗失败4例(12.1％),死亡1例(3.0％).最低抑菌浓度(minimum inhibitory concentration,MIC)<1μg/ml和Cmax/MIC>40的结核病患者治愈率明显高于MIC≥1μg/ml和Cmax/MIC≤40的结核病患者,差异有显著性(P<0.05).利奈唑胺导致的药物不良反应多发生在6个月内,其中周围神经病变(60.6％)最常见.体重≤60kg的患者不良反应发生率明显高于体重>60kg的患者(P<0.05).结论 利奈唑胺具有良好的体内抗结核活性,不良反应发生率较高.MIC和Cmax/MIC可能与治疗效果相关,体重可能与不良反应发生率相关.

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.

BACKGROUND:The emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programs.METHODS:We carried out a prospective, randomized, multicenter study in China that was focused on the potential of a shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. There were 135 MDR-TB cases that met eligibility requirements and were randomly stratified into either the control group or experimental group. Patients in the control group received an 18-month treatment regimen, whereas patients in the experimental group received a 12-month treatment regimen containing CFZ.RESULTS:At the completion of the treatment period, the difference in sputum-culture conversion rates between the experimental group and the control group was not significant. Notably, by the end of 3 months of treatment, 68.7% patients receiving the experimental regimen had sputum-culture conversion, as compared with 55.9% of those receiving the control regimen; this was a significant difference, suggesting an early sputum conversion (P = .04). There were 67 adverse events reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group. No significant difference in the overall incidences of adverse events was observed between the 2 groups.CONCLUSIONS:The MDR-TB patients treated with the shorter regimen containing CFZ had a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned to the experimental group achieved more rapid sputum-culture conversion, reflecting superior antimicrobial activity against MDR-TB.CLINICAL TRIALS REGISTRATION:Chinese Clinical Trial Registry ChiCTR 1800020391.

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.