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.

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.

Esophageal tuberculosis complicated with intestinal tuberculosis: A case report

BACKGROUND Although the overall incidence of tuberculosis in underdeveloped areas has increased in recent years, esophageal tuberculosis(ET) is still rare. Intestinal tuberculosis(ITB) is relatively more common, but there are few reports of ET complicated with ITB. We report a case of secondary ET complicated with ITB in a previously healthy patient.CASE SUMMARY A 27-year-old female was hospitalized for progressive dysphagia, retrosternal pain, acid regurgitation, belching, heartburn, and nausea. Upper gastrointestinal endoscopy showed a mid-esophageal ulcerative hyperplastic lesion. Endoscopic ultrasonography showed a homogeneous hypoechoic lesion, with adjacent enlarged lymph nodes. Biopsy histopathology showed inflammatory exudation,exfoliated epithelial cells and interstitial granulation tissue proliferation.Colonoscopy revealed a rat-bite ulcer in the terminal ileum and a superficial ulcer in the ascending colon, near the ileocecal region. The ileum lesion biopsy showed focal granulomas with caseous necrosis. Polymerase chain reaction for Mycobacterium tuberculosis was positive in the esophageal and ileum lesion biopsies. The T-cell spot tuberculosis test was also positive. The patient was diagnosed with secondary ET infiltrated by mediastinal lymphadenopathy and complicated with ITB, possibly from the Mycobacterium tuberculosis-infected esophageal lesion. After 2 mo of anti-tuberculosis therapy, her symptoms improved significantly, and upper gastrointestinal endoscopy showed healing ulcers.CONCLUSION When dysphagia or odynophagia occurs in patients at high-risk for tuberculosis,ET should be considered.

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.

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

Efficacy of integrating short-course chemotherapy with Chinese herbs to treat multi-drug resistant pulmonary tuberculosis in China: a study protocol

Background:Tuberculosis(TB)causedMycobacterium tuberculosis(M.tb)is one of infectious disease that lead a large number of morbidity and mortality all over the world.Although no reliable evidence has been found,it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect.Methods:Multi-drug resistant pulmonary tuberculosis(MDR-PTB,n=258)patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group(n=172)or control/placebo group(n=86).The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules(1+3 granules),while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo(1+3 placebo granules).In addition,MDR-PTB(n=312)patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment(n=208)or control/placebo(n=104)group.The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules(2+4 granules),while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo(2+4 placebo granules).The primary outcome is cure rate,the secondary outcomes included time to sputum culture conversion,lesion absorption rate and cavity closure rate.BACTEC^(TM)MGIT^(TM)automated mycobacterial detection system will be used to evaluate theM.tb infection and drug resistance.Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data.Discussion:The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects.Chinese herbs have been used for many years to treat MDR-PTB,but are without high-quality evidence.Hence,it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB.Therefore,this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases.It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients.Trial registration This trial was registered at ClinicalTrials.gov(ChiCTR1900027720)on 24 November 2019(prospective registered).

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.

耐药肺结核合并咽炎患者多重耐药α-溶血性链球菌分子流行病学调查及风险模型构建

目的探究耐药肺结核合并咽炎患者多重耐药α-溶血性链球菌分子流行病学调查并构建风险模型。方法选择2019年3月-2022年1月在我院接受治疗的耐药肺结核合并咽炎患者150例为研究对象。采用PhoenixTM-100全自动细菌检测分析系统进行药敏试验。依据脉冲场凝胶电泳(Pulsed field gel electrophoresis,PFGE)和多点位序列分析(Multilocus sequence type,MLST)技术对其中92例多重耐药草绿色链球菌(Viridans Group Streptococcus,VGS)感染患者进行分子流行病学调查。根据是否发生多重耐药感染将患者分为感染组(n=92)和非感染组(n=58),多因素Logistic分析多重耐药VGS感染的独立影响因素并构建简易评分模型划分感染风险等级并进行验证。结果药敏结果显示,VGS对亚胺培南、厄他培南的敏感性高,敏感率为100%;PFGE分型和MLST分型结果显示,92株多重耐药VGS菌株可分为5种PFGE克隆型和15种ST型;多因素Logistic分析结果表明,年龄、呕吐、腹泻、降钙素原、中性粒细胞、白细胞是导致耐药肺结核合并咽炎患者感染多重耐药VGS菌株的独立危险因素(P<0.05);年龄、白细胞、中性粒细胞和降钙素原与多重耐药VGS感染风险关联密切;简易评分模型结果显示其预测效能较好。结论年龄、降钙素原、中性粒细胞、白细胞是感染多重耐药VGS菌株关联最大的独立危险因素,为临床筛查和预防有多重耐药VGS感染风险的耐药肺结核合并咽炎患者提供了理论基础。

Antitubercular therapy in patients with cirrhosis:Challenges and options

Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

肺结核合并2型糖尿病的传染性及耐药性研究

目的探究肺结核合并2型糖尿病的传染性及耐药性。方法选取2023年1月至2023年12月益阳市第四人民医院收治的111名肺结核患者,根据是否合并2型糖尿病,分为单纯肺结核组56名(对照组),肺结核合并2型糖尿病55名(观察组),用沉降吸附法检测痰涂片,魏氏法检测红细胞沉降率(Erythrocyte sedimentation Rate,ESR),结核菌固体培养法(简单法)培养结核分枝杆菌,Xpert检测法及结核分枝杆菌固体药敏实验评价耐药性。评估两组之间结核慢培、痰结核菌涂片、红细胞沉降率、耐药性差异。结果痰结核菌涂片对照组阳性率为66.1%,观察组为87.3%(P<0.05);对照组ESR均值为36.3 mm/h,观察组均值为57 mm/h(P<0.05);对照组耐药人数占5.4%,观察组占21.8%(P<0.05);经logistic回归分析显示,观察组的肺叶累积数目及结核空洞数目更多(P<0.05)。结论较单纯肺结核患者而言,合并2型糖尿病使得肺结核的传染性及活动性更强,耐药发生率更高,病情更加严重。

老年肺结核合并肺炎的病原菌分布、耐药性及影响因素分析

目的 分析老年肺结核合并肺炎的病原菌分布、耐药性及影响因素。方法 回顾性分析2020年6月至2022年12月河北省沧州市第三医院收治的270例老年肺结核患者临床资料,分析患者痰液标本病原菌分布情况及耐药性。根据是否合并肺炎将患者分为合并组与未合并组,对比两组临床资料,采用多因素Logistic回归分析老年肺结核患者合并肺炎的影响因素。结果 270例老年肺结核患者中,65例合并肺炎的患者纳入合并组,其余205例未合并肺炎患者纳入未合并组。合并组患者的65份痰液标本共分离出72株菌株,革兰阴性菌45株,占62.50%,以肺炎克雷伯菌、铜绿假单胞菌为主;革兰阳性菌22株,占30.56%,以金黄色葡萄球菌、溶血葡萄球菌为主;真菌5株,占6.94%。合并组中,肺炎克雷伯菌对氨苄西林、头孢唑林具有较高耐药率;铜绿假单胞菌对复方磺胺甲噁唑、氨苄西林、氨苄西林/舒巴坦具有较高耐药率。金黄色葡萄球菌对青霉素、红霉素具有较高耐药率;溶血葡萄球菌对红霉素、青霉素、阿奇霉素具有较高耐药率。合并组有侵入性操作、有长期使用糖皮质激素、有长期使用广谱抗菌药物患者比例高于未合并组,双歧杆菌数量少于未合并组,肠球菌及大肠埃希菌数量多于未合并组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,有侵入性操作、长期使用糖皮质激素、长期使用广谱抗菌药物、双歧杆菌数量减少、大肠埃希菌数量增多均为老年肺结核患者合并肺炎的危险因素(P<0.05)。结论 老年肺结核合并肺炎患者痰液标本病原菌以革兰阴性菌为主,不同病原菌耐药性存在显著差异。肠道菌群紊乱、长期使用糖皮质激素及广谱抗菌药物等因素会增加老年肺结核合并肺炎的发生风险。

2015—2022年天水市肺结核患者耐药情况及利福平耐药特征分析

目的:分析2015—2022年甘肃省天水市肺结核患者耐药情况及利福平耐药特征,为优化耐药结核病卫生政策提供科学依据。方法:采用回顾性研究方法,从“中国疾病预防控制信息系统”子系统“结核病管理信息系统”中收集2015—2022年天水市肺结核患者实验室检测结果、耐药筛查和耐药结核病诊断信息等资料,分析患者病原学阳性率、药物敏感性试验结果和耐药诊断时间等。结果:2015—2022年,天水市共登记活动性肺结核患者8458例,除外结核性胸膜炎的肺结核患者为7895例,病原学阳性率为28.32%(2236/7895),且从2015年的11.33%(177/1562)上升至2022年的61.30%(236/385),呈明显上升趋势(χ_(趋势)^(2)=1014.480,P=0.000);天水市应耐药筛查肺结核患者2360例,实际耐药筛查率为85.00%(2006/2360),从2015年的54.80%(97/177)上升至2022年的93.39%(240/257),呈明显上升趋势(χ_(趋势)^(2)=397.292,P=0.000);天水市耐药检出率为98.90%(1984/2006),利福平耐药检出率为15.73%(312/1984),从2015年的10.42%(10/96)上升至2017年的28.57%(62/217),再下降至2022年的11.34%(27/238),呈先上升后下降趋势(χ_(趋势)^(2)=27.248,P=0.000)。312例利福平耐药患者中,男性[198例(63.46%)]多于女性[114例(36.54%)];年龄相对集中在20~29岁[85例(27.24%)]和40~49岁[66例(21.15%)],且老年患者(60~83岁)比例从2016年的9.52%(2/21)上升至2022年的25.93%(7/27),呈明显上升趋势(χ_(趋势)^(2)=4.801,P=0.028);职业以农民为主[213例(68.27%)];痰涂片结果以涂阳患者居多[215例(68.91%)],但痰涂片阳性率从2015年的100.00%(10/10)下降至2022年的59.26%(16/27),呈下降趋势(χ_(趋势)^(2)=17.664,P=0.000)。耐药谱前3位依次为利福平+异烟肼+乙胺丁醇[26.92%(84/312)]、利福平[26.28%(82/312)]和利福平+异烟肼[23.40%(73/312)]。耐药患者诊断时间中位数(四分位数)从2016年的145(91,196)d逐年下降至2019年的21(12,39)d。结论:2015—2022年天水市肺结核患者病原学阳性率和耐药筛查率均呈逐年上升趋势,利福平耐药检出率波动较大,耐药诊断时间明显缩短,建议加大老年肺结核患者利福平耐药筛查力度,以减少耐药肺结核的传播。

GeneXpert MTB/RIF检测技术在新疆结核病防治规划中的应用效果

目的:探索在施行结核病防治“新疆模式”中,全面应用GeneXpert MTB/RIF(简称“GeneXpert”)检测发现肺结核及利福平耐药肺结核的效果。方法:从“中国疾病预防控制信息系统”的子系统“结核病管理信息系统”中,收集2017—2020年新疆维吾尔自治区(简称“新疆”)肺结核登记数据,对全面应用GeneXpert检测的效果进行分析,评价2017-2020年肺结核病原学阳性率、利福平耐药检测率、利福平耐药患者发现水平的变化。结果:GeneXpert设备覆盖率、GeneXpert检测率、病原学阳性率分别从2017年的20.00%(22/110)、0.32%(126/39 261)和20.17%(7919/39 261)提高到2020年的100.00%(110/110)、75.16%(19 610/26 090)和57.94%(15 116/26 090),差异均有统计学意义(χ^(2)=40.705,P<0.001;χ^(2)=174.087,P<0.001;χ^(2)=47.569,P<0.001)。病原学阳性患者数从2017年的7919例提高到2020年的15 116例,仅GeneXpert检测阳性患者数从2017年的6例提高到2020年的7194例,所占比例从0.08%(6/7919)提高到47.59%(7194/15 116),差异有统计学意义(χ^(2)=83.824,P<0.001)。病原学阳性肺结核患者利福平耐药筛查率和GeneXpert耐药检测率分别从2017年的44.49%(3523/7919)和1.85%(65/3523)提高到2020年的99.79%(15 084/15 116)和96.13%(14 501/15 084),差异均有统计学意义(χ^(2)=133.333,P<0.001;χ^(2)=250.893,P<0.001)。结论:GeneXpert检测技术的应用,可以明显提升病原学阳性和利福平耐药肺结核的发现水平,有利于新疆结核病疫情的快速下降。

广州市“十二五”与“十三五”期间利福平耐药肺结核患者发现与治疗情况分析

目的:分析广州市“十二五”与“十三五”结核病防治规划期间利福平耐药肺结核(RR-PTB)患者发现与治疗情况,为进一步制定本地区RR-PTB防治规划提供科学依据。方法:通过“中国疾病预防控制信息系统”子系统“结核病信息管理系统”,按照登记时间导出2011年1月1日至2020年12月31日,即“十二五”(2011—2015年)和“十三五”(2016—2020年)规划期间广州市登记的肺结核患者耐药病案数据(包括性别、年龄、民族、职业、户籍、耐药类型、治疗分类等相关信息),筛选出利福平耐药患者病案,分析患者登记、人群特征、耐药筛查和治疗转归情况。结果:2011—2020年,RR-PTB患者年均登记率为0.71/10万(1152/16286.08万),从2011年的0.31/10万(42/1346.32万)上升至2015年的0.38/10万(60/1594.95万)和2020年的0.97/10万(182/1874.03万),呈逐年上升趋势(χ_(趋势)^(2)=256.395,P<0.001)。其中,“十二五”期间年均登记率为0.34/10万(250/7358.06万),不同年份登记率的差异无统计学意义(χ_(趋势)^(2)=4.674,P=0.322);“十三五”期间年均登记率为1.01/10万(902/8928.02万),不同年份登记率的差异有统计学意义(χ_(趋势)^(2)=38.439,P<0.001)。1152例患者中,以男性(851例,73.87%)、25~34岁青壮年(257例,22.31%)和家政家务及待业(364例,31.60%)为主;流动人口、初治、RR-PTB(除异烟肼耐药)、广泛耐药肺结核比例分别从“十二五”的8.80%(22/250)、11.20%(28/250)、0.00%(0/250)和0.00%(0/250)上升到“十三五”的54.43%(491/902)、37.14%(335/902)、19.84%(179/902)和0.78%(7/902),差异均有统计学意义(χ^(2)=91.370、298.740、97.915、34.096,P值均<0.001)。广州市耐药肺结核高危人群筛查率由2017年的60.91%(148/243)上升至2020年的98.95%(568/574),新发/初治病原学阳性肺结核耐药应筛查率由2018年的83.93%(1410/1680)提高到2020年的94.99%(3222/3392),差异均有统计学意义(χ_(趋势)^(2)=425.043、269.670,P值均<0.001)。纳入治疗、完成治疗和治疗成功的患者比例分别从“十二五”的81.20%(203/250)、2.46%(5/203)和45.81%(93/203)提高到“十三五”的91.02%(821/902)、33.62%(276/821)和67.48%(554/821),治疗失败患者比例从17.73%(36/203)降低至2.68%(22/821),差异均有统计学意义(χ^(2)=19.112、86.809、46.636、58.572,P值均<0.001)。结论:在“十二五”与“十三五”规划期间,广州市RR-PTB的防治工作取得了显著的成效。下一步工作中需继续坚持政府主导、多部门合作和全社会共同参与的原则,切实落实结核病防治规划要求,加强结核病防治服务体系建设。

肺结核患者结核分枝杆菌耐药的影响因素

目的:分析肺结核患者结核分枝杆菌耐药的影响因素。方法:回顾性分析2020年4月至2023年4月于泉州市第一医院就诊的100例肺结核患者的临床资料,采集患者入院24 h内的晨痰行细菌培养和药敏试验,根据结核分枝杆菌是否耐药分为耐药组(n=40)和敏感组(n=60),分析结核分枝杆菌耐药的影响因素。结果:100例肺结核患者中结核分枝杆菌耐药40例,耐药率为40.00%,其中耐多药结核病占80.00%;两组性别、年龄、体质量指数、婚姻、病程、饮酒史、高血压、长期应用糖皮质激素、侵入性操作、病变累及肺叶数比较,差异均无统计学意义(P>0.05);两组居住地、吸烟史、糖尿病、空洞肺结核、复治肺结核情况比较,差异均有统计学意义(P<0.05);Logistic回归分析结果显示,居住农村、吸烟、合并糖尿病、空洞肺结核、复治肺结核均为肺结核患者结核分枝杆菌耐药的危险因素(OR>1,P<0.05)。结论:居住农村、吸烟、合并糖尿病、空洞肺结核、复治肺结核均为肺结核患者结核分枝杆菌耐药的危险因素。

含新药口服短程方案治疗耐多药/利福平耐药结核病三例并文献复习

目的:探讨含新药口服短程方案治疗耐多药/利福平耐药结核病的疗效和安全性,为临床医师应用该方案治疗提供更多的依据。方法:回顾性分析2023年12月北京胸科医院收治的3例应用含新药口服短程方案(贝达喹啉、康替唑胺、德拉马尼)治疗的耐多药/利福平耐药结核病患者的相关临床资料,通过查阅中国知网、万方数据库及PubMed数据库,以“耐多药结核、康替唑胺”和“耐多药结核、贝达喹啉、德拉马尼”为中文关键词,以“contezolid、multidrug-resistant tuberculosis”及“multidrug-resistant tuberculosis、bedaquiline、delamanid”为英文关键词进行文献检索,共搜索到国内外相关文献11篇,本研究主要选取含新药康替唑胺、德拉马尼、贝达喹啉短程治疗的文献8篇,结合本组3例患者的病历资料进行有效性和安全性分析。结果:有效性分析显示,含康替唑胺方案治疗的患者中,84%的患者痰培养和(或)涂片结核分枝杆菌阴性,且持续为阴性。治疗期间胸部CT检查显示病灶缩小,停药后胸部CT检查提示病灶稳定。含贝达喹啉、德拉马尼方案治疗的患者中,91%的患者获得了良好的结果。在治疗第8周,痰结核分枝杆菌培养阴转率为95%,第24周时为95%。贝达喹啉联合德拉马尼组的痰涂片和培养阴转中位时间均快于贝达喹啉组。安全性分析显示,含康替唑胺方案治疗的患者未发生骨髓抑制、周围神经病变和视神经病变等在内的利奈唑胺常见不良反应。而在含贝达喹啉和德拉马尼治疗的患者中,QTcF间期相比基线延长了20.7ms(平均16.1~25.3ms),2例患者出现QT间期延长大于500ms,4例患者发生6次QTcF间期延长超过基线值60ms,在治疗期间没有发生3级或4级不良QTc延长事件,未发生心律失常,没有一例永久停药,也没有发生死亡。贝达喹啉联合德拉马尼组QTc间期延长少于贝达喹啉组。在治疗过程中,52%的患者出现骨髓抑制,42%的患者出现周围神经病变。在48周随访时,大多数不良事件得到解决。结论:含新药贝达喹啉、德拉马尼、康替唑胺的全口服方案在耐药结核病短程治疗中取得了较好的效果。治疗期间仅出现轻度药物不良反应,经对症治疗后均缓解,未出现严重药物不良反应。

观察肺结核患者采用水飞蓟宾胶囊预防抗结核药物肝损害的临床效果

目的 探讨对肺结核患者采用水飞蓟宾胶囊预防抗结核药物肝损害的临床效果。方法 100例肺结核患者作为研究对象,根据入院治疗时间顺序分为实验组和对照组,各50例。对照组通过常规的抗结核方式治疗,实验组以对照组为基准增加水飞蓟宾胶囊治疗。比较两组患者的肝功能指标[谷氨酰转肽酶(GGT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)],不良反应发生情况,治疗效果,治疗满意度。结果 治疗后,实验组患者的ALT、AST、GGT、TBil水平显著低于治疗前,对照组患者的ALT、AST、GGT、TBil水平均高于治疗前,且实验组患者的ALT(34.65±6.23)U/L、AST(37.25±8.26)U/L、GGT(7.29±1.69)U/L、TBil(15.27±4.79)μmol/L均低于对照组的(44.76±7.15)U/L、(46.39±9.50)U/L、(12.47±3.01)U/L、(22.31±6.05)μmol/L,经统计学软件分析得出(P<0.05)。实验组不良反应发生率(14%)与对照组(18%)比较差异不大,经统计学软件分析得出(P>0.05)。治疗后,实验组总有效率(86%)高于对照组(68%),经统计学软件分析得出(P<0.05)。实验组治疗满意度(94%)高于对照组(76%),经统计学软件分析得出(P<0.05)。结论 水飞蓟宾胶囊对肺结核患者抗结核药物肝损害具有积极的预防作用,能减少不良反应的发生,可增强患者的治疗效果并提高患者的满意度,值得在临床上推广。

青藏高原肺结核合并念珠菌感染患者的病原菌分布特点及耐药率分析

目的研究青藏高原肺结核患者中机会性念珠菌病原学分布特点及耐药情况。方法分析2020年3月1日至2020年12月31日青海省第四人民医院3012例住院肺结核患者,收集痰标本,采用VITEK-32-YBC全自动细菌分析系统进行念珠菌鉴定,并对检出的念珠菌进行药敏试验。结果在本次调查的3012例肺结核患者中,合并念珠菌感染的肺结核患者有283例,占9.40%。其中,念珠菌类型又以白念珠菌为主,占总数的79.86%。结论青藏高原地区肺结核合并念珠菌感染的患病率较高。因此,选择抗菌药物要根据患者的情况综合分析,以此来选择最佳、最有效的药物治疗方法。

2011—2020年北京市怀柔区耐药结核病高危人群利福平耐药筛查情况分析

目的:通过筛查耐药结核病高危人群,了解北京市怀柔区耐药结核病高危人群利福平耐药情况。方法:统计2011—2020年登记管理的肺结核患者中耐药结核病高危人群筛查情况,包括筛查对象、结核菌培养及药敏试验,对耐药高危人群利福平耐药情况进行分析。结果:2011—2020年北京市怀柔区共登记利福平耐药高危人群130例,完成耐药筛查130例,筛查率为100.00%。实验室污染率为3.08%,其中,涂阳培阴率为34.62%,主要体现在治疗2个月及以上的痰涂片或培养仍为阳性的初治患者中;耐药结核病高危人群培养阳性81例,菌种鉴定为结核分枝杆菌75例,检出利福平耐药23例,检出率为30.67%,明显高于与同期初治培养阳性的肺结核患者利福平耐药检率的3.33%,差异有统计学意义(χ^(2)=40.82,P<0.05)。结论:北京市怀柔区积极开展监测,使利福平耐药结核病能够得到有效的管理和医治,做到早发现、早治疗,避免因贫致病、因病返贫,更重要的是能够有效遏制利福平耐药肺结核的传播风险,减少对人们健康的危害。