Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Clinical Study of Drug-resistant Pulmonary Tuberculosis Treated by Combination of Anti-Tuberculosis Chemicals and Compound Astragalus Capsule(复方黄芪胶囊)

Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

Objective To investigate the prevalence of primary drug-resistant tuberculosis（TB） and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis（MDR-TB）. Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75（80.6%） isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65（69.9%） isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine（31.2%） primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Clinical efficacy and computed tomography diagnostic value of bedaquiline-containing regimens in the treatment of drug-resistant pulmonary tuberculosis

Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retrospectively analyzed the clinical diagnosis,treatment,and CT imaging data of patients with drug-resistant pulmonary tuberculosis treated in Wenzhou Central Hospital from 1 January to 31 December 2022.According to whether the treatment regimen contained bedaquiline,the patients were divided into an observation group(bedaquiline tablets t background regimen)and a control group(background regimen).The clinical efficacy and pulmonary CT changes before and after treatment were analyzed in both groups.Results:After 24 weeks of treatment,there was no statistically significant difference in the white blood cell count or concentrations of hemoglobin,alanine aminotransferase,serum albumin,or creatinine between the two groups(t=0.71,0.93,0.05,0.18,and 0.08,respectively;p>0.05).After 4,8,and 12 weeks of treatment,there was no statistically significant difference in the sputum culture-negative conversion rate between the two groups(χ^(2)=2.67,0.48,and 1.82,respectively;p>0.05).At 24 weeks of treatment,the sputum culture-negative conversion rate in the observation group reached 100%,which was significantly higher than that in the control group(χ^(2)=3.97,p<0.05).The effective absorption rates on chest imaging in the two groups of patients at 12 weeks were 83.33% and 57.89%,respectively.At 24 weeks of treatment,the effective absorption rates were 88.00% and 65.85% in the two groups,with a statistically significant difference(χ^(2)=3.98;p<0.05).There were significant differences in cavity absorption at 24 weeks(χ^(2)=4.33,p<0.05)and 48 weeks after treatment(χ^(2)=10.63,p<0.05).Conclusion:The addition of bedaquiline to the background regimen improved the sputum culture-negative conversion rate and chest imaging effective rate.Patients achieved good results at the end of the 24-week treatment period.

4th National Anti-tuberculosis Drug Resistance Survey in Kenya

Introduction： Recently rapid development of drug resistant TB, particularly MDR TB （Multi Drug Resistant TB） and XDRTB （Extensively Drug-Resistant TB） possess a major threat to control of tuberculosis globally. Information on the extent of MDR-TB from Kenya is largely limited due to several factors. Monitoring of development of resistance is a vital tool in providing critical information for effective planning for TB control and in management of patients infected with TB. Methods： Cross-sectional with cluster design. Results： A total of 2,171 participants recruited into the study from 50 selected clusters. Prevalence of rifampicin resistance for new cases was 1.3% [95% CI, 0.8-2.0] and INH resistance was 5.5% [95% CI, 4.5-6.7]. MDR TB was found in 0.67% of new cases and 2.1% amongst previously treated TB cases. Discussion： Resistance to isoniazid in Kenya has been on the decline due to introduction of rifampicin in combined therapy. There was increase of MDR TB among new cases by 24% and decline in previously treated cases due to lethal impact of HIV. Conclusions： Although drug resistance TB is a growing problem in Kenya, resistance to isoniazid and rifampicin MDR TB is less than previously estimated. The country should continue to monitor drug resistance and ensure effective use of anti TB medicines.

An epidemiological study of resistant tuberculosis in Chongqing,China

Background The epidemiological characteristics of drug-resistant tuberculosis （DR-TB） is fundamental to improving the prevention and control of DR-TB. Mutations in katG315 is thought to be the most predictive molecule markers for Isoniazid （INH） resistance in Mycobacterium tuberculosis （MTB）. However, mutations to these genes have not been thoroughly studied in China, and epidemiological evidence of their expression levels are especially lacking in the southwest of China, which has a high TB burden within the population. Methods MTB isolates were obtained from patients with active pulmonary tuberculosis at the TB dispensary and Chest hospital in Chongqing city between June 2003 and June 2006. Proportion methods were used to test the sensitivity to INH, RFP, SM and EMB of cultured MTB. A total of 100 MTB isolates were also randomly selected for analysis of the molecular mutation spectrum of katG by DNA sequencing. Results Totally 1 089 MTB isolates that completed positive sputum cultures and evaluated for their sensitivity to the four first-line drugs among 2 777 patients with TB. The prevalence of DR-TB and multi-drug resistant tuberculosis （MDR-TB） were 27.7% （302/1 089） and 7.3% （79/1 089）, respectively. The resistance to anti-TB drugs was found to be highest for SM （16.3%） and INH （14.0%）. There was also a significant increase in the prevalence of resistance to RFP and EMB （P〈0.01）, and an increase in MDR-TB between June 2003 and June 2004 and between July 2005 and June 2006. The total mutation rate of katG315 was 75＂5% （37/49） in INH-resistant MTB, and mutation sites included $315T, $315N and $315I with mutation rates of 81.1% （30/37）, 13.5% （5/37） and 5.4% （2/37）, respectively No katG315 mutants were found in any of the 48 INH-sensitive MTB. Our preliminary diagnostic results suggest that mutations in katG315 may potentially serve as molecular markers that can be used to diagnose the resistance to anti-TB drug of INH. Conclusion In the Chongqing, DR-TB and MDR-TB are increasing, and are becoming key problems for tuberculosis control. The use of katG315 mutations as potential molecule markers for drug resistance to INH may help improve patient treatment and decrease the spread of the disease

Prevalence of Mycobacterium tuberculosis Strains Isolated from Both Pulmonary and Extra Pulmonary Samples and Their Resistance to Rifampicin: A Study from Kolkata and Surrounding Suburbs

Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.

肺结核患者氟喹诺酮类耐药影响因素预测模型的构建与验证:基于LASSO-Logistic回归模型

背景利福平耐药/耐多药结核病(RR/MDR-TB)治疗困难,治愈率低,且传染性强,氟喹诺酮类(FQs)作为治疗RR/MDR-TB的核心药物,耐药趋势严峻,对FQs影响因素进行分析有助于提高RR/MDR-TB的治愈率,并控制准广泛耐药(pre-XDR)和广泛耐药结核病的发生。目的分析住院肺结核患者FQs耐药情况及影响因素,构建FQs耐药危险因素的列线图(Nomogram)预测模型并进行验证。方法回顾性选取于2021年1月—2022年2月在贵阳市公共卫生救治中心住院且有药物敏感试验结果的583例肺结核患者为研究对象。根据治疗史将患者分为初治组(296例)和复治组(287例);根据FQs耐药情况将患者分为FQs耐药组(63例)和FQs敏感组(520例)。分析患者对13种抗结核药物总耐药分布情况,比较FQs耐药组与FQs敏感组肺结核患者的基线特征。采用LASSO回归模型筛选特征变量后,行多因素Logistic回归分析FQs耐药的独立危险因素,并构建Nomogram预测模型;采用受试者工作特征(ROC)曲线下面积(AUC)、校准曲线对其进行验证。结果583例患者中FQs敏感520例,耐药63例,耐药率为10.81%,仅次于一线抗结核药异烟肼、利福平、链霉素、乙胺丁醇总耐药率(36.36%、32.76%、21.61%、12.86%)。复治组患者利福平、异烟肼、乙胺丁醇、链霉素、左氧氟沙星、莫西沙星、利福平耐药(RR)、耐多药(MDR)、pre-XDR耐药率高于初治组(P<0.05)。FQs耐药组患者其他民族、复治、艾滋病、吸毒史、空洞、咯血、不规则抗结核史、MDR占比高于FQs敏感组(P<0.05)。LASSO回归筛选出6个变量:民族、治疗史、艾滋病、吸毒史、咯血、MDR;多因素Logistic回归分析结果显示,其他民族(OR=2.313,95%CI=1.153~4.640,P=0.018)、复治(OR=1.892,95%CI=1.005~3.560,P=0.048)、咯血(OR=1.941,95%CI=1.087~3.465,P=0.025)、MDR(OR=3.342,95%CI=2.398~7.862,P<0.001)是肺结核患者FQs耐药的独立危险因素;Logistic回归方程Logit(P)=-3.571+0.838×民族+0.638×治疗史+0.663×咯血+1.468×MDR,基于此构建风险Nomogram预测模型,AUC为0.796(95%CI=0.717~0.876),Bootstrap法验证平均绝对误差为0.015,通过Hosmer-Lemeshow拟合优度检验,预测模型有较好的校准能力(χ^(2)=3.426,P=0.489)。结论肺结核患者FQs耐药率较高,其他民族、复治、咯血、MDR是肺结核患者FQs耐药的独立危险因素,构建Nomogram预测模型对于肺结核患者FQs耐药具有较好的预测价值,能够为临床诊断耐药结核病及为RR/MDR-TB制订合理治疗方案提供新思路。

抗γ-干扰素自身抗体阳性耐多药结核病并发马尔尼菲等多重感染一例并文献复习

目的: 报告1例抗γ-干扰素自身抗体阳性导致的耐多药结核病并发马尔尼菲等多重感染患者的诊治过程,并结合文献分析该病的临床特征、实验室检查、治疗及预后。方法: 回顾性分析2023年8月2日首都医科大学附属北京胸科医院收治的1例抗γ-干扰素自身抗体阳性导致的耐多药结核病并发马尔尼菲等多重感染患者的相关临床资料。检索截止时间2024年5月31日,分别从PubMed数据库中以“Anti-interferon-γ autoantibodies、Multidrug-resistant tuberculosis”同时为检索词,从万方数据库、中国知网以“抗γ-干扰素自身抗体、耐多药结核病”同时为检索词均未检索到相关文献。而以“抗γ-干扰素自身抗体、Anti-interferon-γ autoantibodies”分别为中英文关键词在万方数据库、中国知网和PubMed数据库进行检索,共检出抗γ-干扰素自身抗体并发药物敏感结核病2篇,检出抗γ-干扰素自身抗体并发机会性感染61篇,检出抗γ-干扰素自身抗体相关治疗17篇。总结该例患者特征并进行相关文献复习。结果: 该患者经过免疫评估,发现细胞免疫异常、基因突变,因药物不良反应和患者身体一般情况较差,错过最佳治疗时机,未达到理想效果。结合文献研究,65例并发两种及以上机会性感染,50例存在皮肤损害,而抗γ-干扰素自身抗体并发耐多药结核病患者既往无相关文献报道。文献报道中抗γ-干扰素自身抗体阳性的获得性免疫缺陷综合征患者中,机会性感染病原中马尔尼菲篮状菌病71例,非结核分枝杆菌病31例,结核病2例。其中,65例患者并发两种及以上机会性感染,50例患者存在皮肤损害。结论: 抗γ-干扰素自身抗体阳性患者可能合并多重感染,治疗效果差,尽早应用新型免疫制剂联合相关病原体治疗可能获得更好的预后。

Comparison of Two Molecular Assays For Detecting Smear Negative Pulmonary Tuberculosis

Objective To compare the performance of MTBDRplus V2 and Xpert MTB/RIF for detecting smear negative pulmonary tuberculosis （PTB）. Methods Clinical PTB suspects were enrolled consecutively in Anhui Chest Hospital and Xi＇an Chest Hospital from January to December in 2014. The sputum samples of smear negative PTB suspects were collected and decontaminated. The sediment was used to conduct MTBDRplus V2, Xpert MTB/RIF and drug susceptibility test （DST）. All the samples with discrepant drug susceptibility result between molecular methods and phenotypic method were confirmed by DNA sequencing. Results A total of 1973 cases were enrolled in this study. The detection rates of Mycobacterium tuberculosis complex （MTBC） by MTBDRplus V2 and Xpert MTB/RIF were 27.67% and 27.98%, respectively. When setting MGIT culture result as a gold standard, the sensitivity and specificity of MTBDRplus V2 were 86.74% and 93.84%, and the sensitivity and specificity of Xpert MTB/RIF were 86.55% and 93.43%, respectively. For the detection of the resistance to rifampin, the sensitivity and specificity of MTBDRplus V2 were 94.34% and 96.62%, and the sensitivity and specificity of Xpert MTB/RIF were 88.68% and 95.96%, respectively. For the detection of the resistance to isoniazid, the sensitivity and specificity of MTBDRplus V2 were 77.38% and 98.02%, respectively. Conclusion MTBDRplus V2 and Xpert MTB/RIF can be used to detect MTBC in smear negative samples with satisfactory performance.

MDR-Chin研究解析:耐多药肺结核全口服短程治疗方案在中国的应用前景

全球耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)的治疗研究趋势是缩短疗程。MDR-Chin研究是中国第一项探索全口服短程方案治疗MDR-TB和准广泛耐药结核病(pre-extensive drug-resistant tuberculosis,pre-XDR-TB)的队列研究,主要验证了3种不同治疗方案的有效性和安全性。结果表明,在停药后12个月的随访期内,96%的MDR-TB患者和83.3%的pre-XDR-TB患者达到了良好结局;总体良好结局率为92.9%。虽然3级或更高级别的不良事件很常见(48.1%),但大多可管可控,且严重不良事件较少(7.7%)。该研究保持了低失访率,体现了全口服短程方案的优势,并展示了在资源有限的环境中的应用潜力。本文中,笔者介绍了MDR-Chin研究的概况,分析其优点和缺点,并探讨全口服短程治疗方案在中国实施的可能性及未来的临床研究方向。

Anti TB drug resistance in Tanga,Tanzania:a cross sectional facility base prevalence among pulmonary TB patients

Objective:To determine the prevalence and risk factors associated with drug resistance tuberculosis(TB) at facility-base level in Tanga,Tanzania.Methods:A total of 79 Mycobacterium tuberculosis(MTB) isolates included in the study were collected from among372(312 new and 60 previously treated) TB suspects self referred to four TB clinics during a prospective study conducted from November 2012 to January 2013.Culture and drug susceptibility test of the isolates was performed at the institute of medical microbiology and epidemiology of infectious diseases,University hospital,Leipzig,Germany.Data on the patient's characteristics were obtained from structured questionnaire administered to the patients who gave informed verbal consent.Unadjusted bivariate logistic regression analysis was performed to assess the risk factors for drug resistant-TB.The significance level was determined at P<0.05.Results:The overall proportions of any drug resistance and MDRTB were 12.7%and 6.3%respectively.The prevalence of any drug resistance and MDRTB among new cases were 11.4%and 4.3%respectively,whereas among previously treated cases was 22.2%respectively.Previously treated patients were more likely to develop anti-TB drug resistance.There was no association between anti-TB drug resistances(including MDRTB) with the risk factors analysed.Conclusions:High proportions of anti TB drug resistance among new and previously treated cases observed in this study suggest that,additional efforts still need to be done in identifying individual cases at facility base level for improved TB control programmes and drug resistance survey should continuously be monitored in the country.

A pilot study on prevalence and cure rate of tuberculosis in selected areas of Malabar 2006-07.

Objective:To study the prevalence and cure rate of tuberculosis(TB) and the people affected by TB in selected areas,considering different factors like age,sex,percentage of people affected,dosage forms,role of hospitals, and patient category.Methods:A detailed survey was carried out in and around Perinthalmanna and Wayanad(Urban and Rural) to understand the burden and overall trend of TB in our locality and how effective our TB control programme.More than 250 treatment cards were collected from the Government hospitals and TB Sanatorium.Results:In the study,at Perinthalmanna and Wayanad,out of 250 TB patients it was found that males is more susceptible than females,rural area accounting for the greater proportion of TB patients. Greater proportion were affected with pulmonary than extra pulmonary Tuberculosis.The incidence of tuberculosis in different age groups varied according to the area.Half proportion in both rural and urban areas were belonging to categoryⅡfollowed by categoryⅢ.Conclusion:The nature and magnitude of TB is more in rural area than urban area mainly because of the lack of awareness of the severity of disease and improper follow up of preventive measures.Our study suggests that the combined and committed efforts of government,non government organizations,medical and paramedical professional and society is required at large,to reach all patients and ensure that they receive high quality care.

肺超声特征及血清miR-132、miR-432水平与耐药肺结核抗结核疗效的关系

目的探讨肺超声特征及血清微小RNA-132(miR-132)、微小RNA-432(miR-432)与耐药肺结核(DR-PTB)抗结核疗效的关系。方法选取2020年1月至2023年4月黑龙江省传染病防治院收治的85例DR-PTB患者作为研究对象。所有患者入院后均进行规范化抗结核治疗,治疗前进行肺超声检查,分析肺超声特征,比较不同肺超声特征患者血清miR-132、miR-432水平。统计治疗6个月后抗结核疗效,根据结核分枝杆菌培养结果,将患者分为疗效良好组和疗效不良组,比较疗效良好组和疗效不良组临床资料。采用受试者工作特征(ROC)曲线分析血清miR-132、miR-432对DR-PTB患者抗结核疗效不良的预测价值。结果85例DR-PTB患者中,胸膜下实变:单个29例(34.12%),多个56例(65.88%);胸膜下结节64例(75.29%);胸膜增厚68例(80.00%);空洞38例(44.71%);胸腔积液20例(23.53%);肺尖实变46例(54.12%)。多个胸膜下实变、有胸膜下结节、有胸膜增厚、有空洞、有胸腔积液、有肺尖实变患者患者血清miR-132、miR-432水平高于单个胸膜下实变、无胸膜下结节、无胸膜增厚、无空洞、无胸腔积液、无肺尖实变患者,差异均有统计学意义(P<0.05)。结核菌培养结果显示,疗效不良组有37例患者,疗效良好组有48例患者。疗效不良组复治、耐多药、有空洞患者比例及血清miR-132、miR-432水平高于疗效良好组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清miR-132、miR-432单独预测DR-PTB患者抗结核疗效不良的曲线下面积(AUC)分别为0.768、0.744;血清miR-132、miR-432联合预测DR-PTB患者抗结核疗效不良的AUC为0.921;联合预测的AUC大于血清miR-132、miR-432单独预测的AUC(Z_(联合-miR-132)=2.368,P=0.018;Z_(联合-miR-432)=2.723,P=0.007)。结论血清miR-132联合miR-432对DR-PTB患者抗结核疗效不良的预测价值较高,且高于单项指标的预测价值。

Tuberculosis treatment-new approach to an old problem

Chronic mycobacterium infections are major causes of disease burden of 20%in a tropical country like India. The inflammatory cascade following these bacterial infections often leads to tissue damage and perpetuates necrosis, fibrosis and the disease process.Pulmonary tuberculosis,multi-drug resistant tuberculosis not only affects individuals but society at large.Current remedial measures using various technology platforms singularly did not produce effective and appreciable reduction in global disease burden.On the contrary,the conventional chemotherapeutic chemical moieties have demonstrated variable pharmacogenomic expression,increased drug resistance,non compliance of strict prolonged drug regimens with debilitating side effects and contraindications. Furthermore,secreted inflammatory cytokines results in chronic infection,immune deviation,and immunopathology in the lungs.Hence,identification of immune escape mechanisms leading to chronic mycobacterial infections is crucial for development of new treatments.The review would dwell into the basic pathogenic mechanism and the newer approaches that may need to be considered for developing novel therapeutic strategies.

The History of Tuberculosis: Past, Present, and Future

Tuberculosis (TB), transmitted by the bacteria Mycobacterium tuberculosis has been a global epidemic for years. The evidence for infection with TB is centuries old. It can have an indolent course, and may remain inactive for years in individuals with the possibility of reactivation at any time, causing widespread systemic symptoms. The treatment and management of TB has become more effective over the years. It is estimated that more than one-third of the world population, especially in poor and developing countries are harboring this bacterium with varying manifestations of the disease from no symptoms to life-threatening infections. This manuscript describes the history of the disease and the discoveries. It also includes the recent advances and challenges facing the world and how governments and organizations are working together to control this disease.

肺泡灌洗液中miR-30a-5p、CCL16表达与肺结核患者结核杆菌耐药性的关系

目的 探讨耐药肺结核患者支气管肺泡灌洗液中微小RNA-30a-5p(microRNA-30a-5p, miR-30a-5p)和C-C基序趋化因子配体16(C-C motif chemokine ligand 16, CCL16)表达水平变化,为结核病防治提供理论基础。方法 选取2018年2月1日-2021年6月30日在我院治疗的活动性肺结核患者182例作为研究对象(观察组),并根据是否对结核杆菌耐药情况将其分为耐药组和非耐药组,选择同期90例非肺结核的健康人(因胸痛经纤维支气管镜检查排除肺结核)作为对照组。采用实时荧光定量PCR法检测支气管肺泡灌洗液中miR-30a-5p表达水平,采用ELISA法检测CCL16水平,采用流式细胞分析法检测外周血T细胞亚群分布,采用Pearson分析法分析耐药肺结核患者支气管肺泡灌洗液中miR-30a-5p与CCL16表达水平相关性,采用Logistic逐步回归分析法分析肺结核患者结核杆菌耐药性的影响因素。结果 非耐药组与耐药组CD3^(+)T细胞、CD4^(+)T细胞水平及CD4/CD8比值均显著低于对照组,CD8^(+)T细胞水平显著高于对照组(P均<0.05);耐药组CD3^(+)T细胞、CD4^(+)T细胞水平及CD4/CD8比值均显著低于非耐药组,CD8^(+)T细胞水平显著高于非耐药组(P均<0.05)。非耐药组与耐药组支气管肺泡灌洗液中miR-30a-5p表达水平均显著低于对照组,CCL16水平均显著高于对照组(P均<0.05);耐药组肺泡灌洗液中miR-30a-5p表达水平显著低于非耐药组,CCL16水平显著高于非耐药组(P均<0.05)。有吸烟史、广泛耐药的肺结核患者肺泡灌洗液中miR-30a-5p表达水平显著低于无吸烟史、耐多药的肺结核患者,CCL16水平显著高于无吸烟史、耐多药的肺结核患者(P均<0.05)。Pearson相关性分析显示,耐药肺结核患者肺泡灌洗液中miR-30a-5p与CCL16表达水平呈显著负相关(r=-0.556,P <0.001);Logistics多因素回归分析显示,有吸烟史、肺部空洞、miR-30a-5p <0.72、CCL16≥5.34 pg/ml为影响肺结核患者耐药性的危险因素(P均<0.05)。结论 耐药肺结核患者支气管肺泡灌洗液中miR-30a-5p表达水平降低,CCL16水平升高,检测miR-30a-5p、CCL16水平可反映机体感染结核杆菌后机体发生的免疫应答情况,为耐药肺结核的治疗提供参考。

耐药肺结核患者血清可溶性白细胞分化抗原14、降钙素原、白介素-22水平变化及对抗结核疗效的预测价值

目的:探究耐药肺结核患者血清可溶性白细胞分化抗原14(sCD14)、降钙素原(PCT)、白介素-22(IL-22)水平变化,并分析其对抗结核疗效的预测价值。方法:选取196例肺结核患者为研究对象,根据耐药情况分为耐药组(n=97)和非耐药组(n=99)。比较两组血清sCD14、PCT、IL-22水平,比较耐药组不同临床特征患者血清各指标水平,分析其与耐药肺结核临床特征的相关性。耐药组均根据结核菌培养及药敏试验结果进行规范化抗结核治疗6个月,对比转阴患者、未转阴患者治疗前、治疗1、3、6个月后血清sCD14、PCT、IL-22水平及变化值。分析治疗前后血清指标水平变化值与抗结核疗效的关系及其预测抗结核疗效的价值。结果:耐药组血清sCD14、PCT、IL-22水平高于非耐药组高(均P<0.05);耐药组血清各指标水平与肺部空洞、耐药程度、病情程度呈正相关(均P<0.05);未转阴患者治疗前、治疗1、3、6个月后血清各指标水平高于转阴患者,其水平变化值低于转阴患者(均P<0.05);血清各指标变化值与抗结核疗效呈正相关(P<0.05);治疗3个月后血清各指标变化值联合预测抗结核疗效的AUC大于治疗1个月后血清各指标变化值联合预测的AUC(P<0.05)。结论:耐药肺结核患者血清sCD14、PCT、IL-22水平升高,且与病情严重程度、抗结核疗效有关,联合检测其水平对抗结核疗效具有一定预测价值。

热毒宁注射液联合美罗培南和多黏菌素B治疗MDR-GNB肺部感染的临床疗效和经济学分析

目的:探讨热毒宁注射液联合美罗培南和多黏菌素B治疗多重耐药革兰阴性菌(MDR-GNB)肺部感染的有效性、安全性和经济性。方法:选取2020年10月至2023年1月该院收治的MDR-GNB肺部感染患者130例,按随机数字表法分为对照组和观察组,每组65例。对照组患者予以多黏菌素B联合美罗培南治疗,观察组患者在对照组的基础上加用热毒宁注射液,疗程均为7~14 d。观察两组患者的临床疗效、细菌清除率、临床感染体征改善时间、治疗前后炎症因子变化和不良反应发生情况;并应用成本-效果分析进行经济学评价。结果:观察组患者的临床总有效率、细菌清除率为87.69%(57/65)、92.31%(60/65),显著高于对照组的72.31%(47/65)、75.38%(49/65),差异均有统计学意义(P<0.05)。观察组患者退热时间、咳嗽咳痰消失时间、肺部啰音消失时间、影像学检查改善时间以及治疗时间显著短于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组患者白细胞计数、C反应蛋白、降钙素原和血清样淀粉蛋白A水平显著低于对照组,差异均有统计学意义(P<0.05)。观察组、对照组患者不良反应发生率分别为10.77%(7/65)、7.69%(5/65),差异无统计学意义(P>0.05)。观察组和对照组临床总有效率的成本-效果比(C/E)分别为352.56和577.88,细菌清除率的C/E分别为334.91和554.34;相对于观察组,对照组临床总有效率、细菌清除率的增量成本-效果比分别为-706.80、-642.09。结论:热毒宁注射液能显著提高多黏菌素B联合美罗培南治疗MDR-GNB肺部感染患者的临床疗效,未显著增加不良反应,且具有显著经济学优势。