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.

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.

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.

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.

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。

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。

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。

肺结核继发其他病原菌肺部感染的病原菌特征及耐药性分析

目的分析肺结核继发其他病原菌肺部感染的病原菌特征及耐药性。方法2019年1月至2021年5月莆田学院附属医院收治的320例肺结核继发其他病原学肺部感染患者作为研究对象,取所有患者的痰液或肺泡灌洗液样本进行痰培养,并展开药敏试验。结果320例患者共分离96株病原菌,病原菌分布为革兰阴性菌占比58.33%、真菌占比28.13%和革兰阳性菌占比13.54%。革兰阳性菌以金黄色葡萄球菌和表皮葡萄球菌最常见,对哌拉西林、庆大霉素、左氧氟沙星的耐药性最高,对多粘菌素B、美罗培南和亚胺培南的耐药性低;革兰阴性菌以肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌和大肠埃希菌最常见,对青霉素、苯唑西林、红霉素的耐药性最高,对万古霉素、利奈唑胺和替加环素的耐药性低;真菌以白假丝孝母菌最常见,对酮康唑、氟康唑的耐药性最高,对两性霉素和伏立康唑的耐药性低。结论导致肺结核继发肺部感染的病原菌种类多,需开展病原学检查,并以药敏试验结果为参考合理的选择药物,以确保临床治疗有效性及用药安全性。

耐多药肺结核病患者生命质量及影响因素分析

目的探讨耐多药和利福平耐药肺结核病(multidrug-resistant and rifampin-resistant pulmonary tuberculosis,MDR/RR-PTB)患者的健康相关生命质量(health related quality of life,HRQOL)并分析其影响因素。方法选取2021年至2024年巴中市《结核病管理信息系统》登记治疗管理的50例MDR/RR-PTB患者为耐药组,选取同期该系统登记治疗管理的对抗结核药物治疗敏感的肺结核患者50例作为对照组,采用慢性肺结核患者生命质量测定量表(quality of life instuments for chronic disease pulmonary tuberculosis,QLICD-PT)评估并比较两组患者的HRQOL,用多重线性回归分析法分析影响MDR/RR-PTB患者HRQOL的因素。结果与对照组比较,MDR/RR-PTB组患者除生理功能得分外,其他各模块差异均有统计学意义(P<0.05)。单因素分析结果显示,不同性别、医保类别、家庭月收入、有无合并症、淋巴细胞计数、白蛋白、C反应蛋白、体质量指数的患者QLICD-PT总分差异有统计学意义(P<0.05)。多重线性回归分析结果显示,医保类别、家庭月收入差异有统计学意义(P<0.05)。结论MDR/RR-PTB患者HRQOL低于对抗结核药物敏感的肺结核患者,患者的医保类别、家庭月收入是MDR/RR-PTB患者HRQOL的可能影响因素。

世界卫生组织《耐药结核病和丙型病毒性肝炎治疗的联合管理(2024快讯版)》解读

世界卫生组织于2024年4月9日发布了《耐药结核病和丙型肝炎治疗的联合管理(2024快讯版)》。本文中,笔者介绍了该指南内容的要点,包括耐药结核病与丙型病毒性肝炎共病治疗管理的背景、指南更新的主要关键证据及主要发现,并总结下一步指南更新方向,同时,就该指南在中国临床实践的可行性和未来研究方向提出了思考和讨论。

肝硬化失代偿期合并肺结核的个体化治疗分析与药学监护

1例硬化失代偿期患者持续高热,经验性抗感染治疗效果不佳,临床药师参与制订个体化抗结核+抗感染方案:异烟肼0.3 g qd+利福平0.45 g qd+乙胺丁醇0.75 g qd+左氧氟沙星0.6 g qd,抗结核治疗一周后患者体温恢复正常;治疗两周后,患者胸腔积液较前明显减少,但复查总胆红素升高(61μmol·L^(-1)),考虑患者出现了抗结核药物性肝损伤。临床药师评估病情与肝功能情况,决定继续抗结核治疗,并加用腺苷蛋氨酸保肝治疗,一周后复查胆红素较前未再升高;两周后肝功能显著好转,顺利出院。肝硬化患者的抗结核治疗方案制订需结合患者的病情和抗结核药物的特点进行个体化选择,以寻求获益与风险的平衡。

苦黄注射液预防抗结核药物导致的药物性肝损伤患者疗效研究

目的本研究观察了应用苦黄注射液预防抗结核药物诱发药物性肝损伤(DILI)的作用,以避免不合理的抗痨中断治疗。方法2022年3月~2022年11月我院收治的97例肺结核患者,被随机分为试验组50例和对照组47例。所有患者均接受标准的2HREZ/4HR抗结核治疗,试验组在此治疗的基础上加用苦黄注射液治疗8周。采用ELISA法检测血清白介素6(IL-6)和肿瘤坏死因子-α(TNF-α),采用放射免疫法检测血清血红素加氧酶(HO-1)和超氧化物歧化酶(SOD)水平。结果在治疗4周末,试验适应性肝损伤和DILI发生率分别为6.0%和2.0%,显著低于对照组的17.0%和8.5%(P<0.05),在治疗8周末,试验组适应性肝损伤和DILI发生率分别为6.0%和4.0%,显著低于对照组的21.3%和17.0%(P<0.05);在治疗8周末,试验组血清ALT、AST和TBIL水平分别为(28.4±23.4)U/L、(30.8±18.7)U/L和(12.9±7.3)μmol/L,显著低于对照组【分别为(53.1±33.1)U/L、(52.5±37.7)U/L和(20.1±10.9)μmol/L,P<0.05】;试验组血清HO-1和SOD水平分别为(200.3±14.0)U/L和(418.0±18.7)U/L,显著高于对照组【分别为(128.8±21.4)U/L和(318.0±15.1)U/L,P<0.05】,而血清IL-6和TNF-α水平分别为(11.4±1.9)ng/L和(9.3±1.8)ng/L,显著低于对照组【分别为(17.5±4.0)ng/L和(14.5±3.0)ng/L,P<0.05】。结论在抗痨开始时应用苦黄能够显著降低DILI的发生,尽可能地维持标准化抗结核治疗,且安全性良好。

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。

贝达喹啉联合背景方案治疗耐药肺结核的疗效

目的:探讨贝达喹啉联合背景方案治疗耐药肺结核的疗效。方法:回顾性选择2022年1月至2023年1月广东省广州市胸科医院收治的159例耐药肺结核患者,按随机对照原则分组。对照组(80例)接受常规背景方案治疗,研究组(79例)在其基础上联合贝达喹啉治疗。于6个月后评估两组病灶吸收率、痰菌转阴率及空洞闭合率,对比两组治疗前后血清肝功能指标、心电图QTc变化,统计两组不良反应发生率。结果:研究组病灶吸收率、痰菌转阴率及空洞闭合率均较对照组高(P<0.05)。两组治疗后丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平升高(P<0.05);研究组治疗后ALT、AST水平与对照组相比,差异无统计学意义(P>0.05)。两组治疗后QTcF值升高,心率降低(P<0.05)。且研究组治疗后QTcF值比对照组高,心率比对照组低(P<0.05)。两组转氨酶升高、白细胞减少及胃肠道反应发生率对比,差异无统计学意义(P>0.05);研究组QT间期延长发生率显著高于对照组(P<0.05)。结论:贝达喹啉联合背景方案治疗耐药肺结核的疗效较佳,未引起肝功能指标异常,但QT间期延长发生率较高。