First-Line Drug Resistance Patterns of Mycobacterium tuberculosis Complex Isolates from Re-Treatment Patients from Sudan

Drug susceptibility testing (DST) plays a pivotal role in TB patients’ management leading to the selection of most effective drugs. This study aimed to determine resistance patterns to first line anti-TB drugs in Mycobacterium tuberculosis isolates from re-treated patients from Sudan. A total of 239 sputum specimens were collected from smear positive re-treatment TB patients during the period from July 2009 to July 2010. Specimens were pre-treated according to Petroff method. The recovered isolates were tested for sensitivity to first line anti-TB drugs by the 1% proportion method. One hundred and forty three (143/239, 59.8%) mycobacterial isolates were successfully recovered. The majority (98.6%, 141/143) of the isolates were Mycobacterium tuberculosis complex strains. Two strains (2/143, 1.4%) were identified as RIF/INH-resistant MOTT, while fifty four isolates (38.3%, 54/141) were MDR. Multi- drug resistant Mycobacterium tuberculosis complex (MDR-TB) among re-treatment patients from national referral centers for tuberculosis diagnosis and management was considerably high in the study isolates.

氟喹诺酮类药物联合阿米卡星治疗MDR-TB疗效分析

目的分析和评价氟喹诺酮类药物联合阿米卡星在治疗耐多药结核病(MDR-TB)中的疗效。方法 107例患者随机分为治疗组(54例)和对照组(53例)。治疗组以左氧氟沙星、阿米卡星、丙硫异烟胺、帕司烟肼、吡嗪酰胺治疗方案,对照组以左氧氟沙星、丙硫异烟胺、帕司烟肼、吡嗪酰胺的治疗方案,疗程为24个月。结果 104例患者完成化疗疗程,痰菌阴转率:治疗组与对照组分别为85.5%和54.8%,治疗组显著高于对照组(P<0.01);治疗组与对照组分别为61.4%和41.7%,治疗组显著高于对照组(P<0.01)。结论氟喹诺酮类药物联合阿米卡星更能提高MDR-TB结核患者的痰菌转阴率。

母牛分枝杆菌菌苗联合抗结核药治疗老年MDR-TB疗效分析

目的观察和评价母牛分枝杆菌菌苗在老年MDR-TB免疫治疗中的临床效果。方法 113例老年MDR-TB患者随机分为治疗组(56例)和对照组(57例)。治疗组以阿米卡星、丙硫异烟胺、吡嗪酰胺、莫西沙星、帕司烟肼、母牛分枝杆菌苗治疗方案,对照组以阿米卡星、丙硫异烟胺、吡嗪酰胺、莫西沙星、帕司烟肼的治疗方案,疗程为24个月。结果 104例患者完成化疗疗程,6个月末痰菌阴转率:治疗组与对照组分别为57.7%和44.2%;12个月末痰菌阴转率为78.8%和51.9%;疗程结束痰菌阴转率分别为88.5%和53.8%,治疗组显著高于对照组(P<0.01)。空洞闭合率:治疗组86.5%,对照组57.7%,治疗组显著高于对照组(P<0.01)。结论母牛分枝杆菌菌苗用于老年MDR-TB患者的治疗能显著提高痰菌转阴率和空洞闭合率,有利于病灶吸收,临床上可作为老年MDR-TB的辅助手段。

MDR-TB的化疗和化疗实施

MDR-TB系指同时耐异烟肼(INH)和利福平(RFP),或还耐其他抗结核药的结核病.解决MDR-TB的化疗问题有两条路:一是研究开发新抗结核药;二是用好现有常用抗结核药,组成更为有效的治疗MDR-TB的标准化疗方案.本文仅就后者进行探讨,并提出标准化疗方案和化疗实施的规范化要求.

Pre-Extensively Drug Resistant Tuberculosis (Pre-XDR-TB) among Pulmonary Multidrug Resistant Tuberculosis (MDR-TB) Patients in Bangladesh

Background & Objectives: Emergence of drug resistant Tuberculosis (TB) is a major obstacle in the TB control programme of Bangladesh. This study was carried out to detect pre-extensively drug resistant TB (pre-XDR-TB) cases among the multidrug resistant TB (MDR-TB) patients in Bangladesh, as the early detection of pre-XDR-TB can guide clinicians in the appropriate modification of MDR-TB treatment regimen with effective drugs to prevent treatment failure. Methodology: A total of 68 MDR-TB cases were enrolled in this study. Multiplex Real-time PCR was done to detect pre-XDR-TB cases directly from sputum samples of MDR-TB patients. Results: Out of 68 MDR-TB cases 11 (16.18%) cases were detected as pre-XDR-TB. The resistant profile of the 11 pre-XDR-TB revealed 9 (81.82%) cases of fluoroquinolone (FLQ) resistant pre-XDR-TB and 2 (18.18%) cases of injectable second line (ISL) agent resistant pre-XDR-TB. Out of 11 pre-XDR-TB cases 7 (63.64%) cases had history of taking treatment for MDR-TB regularly, 1 (9.09%) case had history of taking treatment for MDR-TB irregularly and 3 (27.27%) cases had no history of taking treatment for MDR-TB. Conclusion: This study encountered a high rate of pre-XDR-TB cases along with a significant number of primarily resistant bacilli which is of concern in the management of MDR-TB. It is evident that Bangladesh is in urgent need to device strategies for rapid and early detection of pre-XDR-TB in order to prevent treatment failure of MDR-TB cases and also to halt the progression of MDR-TB cases to extensively drug resistant TB (XDR-TB), which is not only difficult but also very expensive to treat.

重庆市新结防模式下MDR-TB患者治疗现状及经济负担调查研究

本研究评估重庆市在新结防模式下MDR-TB患者的治疗现状及经济负担,为MDR-TB控制提供决策依据。研究表明患者接受正规治疗的比例较高,医保覆盖率也较高,但也还存在相关卫生服务可及性差、治疗副反应普遍、患者经济负担较重等问题。后续应加强重点人群和弱势人群MDR-TB的筛查,提升相关卫生服务的可及性,同时需要加强对患者的经济支持。

Smear-Negative Multidrug-Resistant Tuberculosis a Significance Hidden Problem for MDR-TB Control: An Analysis of Real World Data

Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-positive TB. Materials and Methods: Medical records information of 6977 cases was included from 11,950 inpatients from January 2009 to November 2013. The cases data were divided into a training set, test set and prediction set. Logistic regression analysis was applied to the training set data to establish a prediction classification model, the effect of which was then evaluated using the test set by receiver operating characteristic (ROC) analysis. The model was then applied to the prediction set to identify incidence of snMDR-TB. Results: Sixteen factors which correlate with MDR-TB-including frequency of hospitalization, province of origin, anti-TB drugs, and complications, were identified from the comparison between SP-TB and spMDR-TB. The area under the ROC curve (AUC) of the prediction model was 0.752 (sensitivity = 61.3%, specificity = 83.3%). The percentage of all inpatients with snMDR-TB (snMDR-TB/Total) was 28.7% ± 0.02%, while that of all SN-PTB with snMDR-TB (snMDR-TB/SN-PTB) was 26.5% ± 0.03%. The ratio of snMDR-TB to MDR-TB (snMDR-TB/MDR-TB) was 2.09 ± 0.33. Conclusion: snMDR-TB as an important source of MDR-TB is a significant hidden problem for MDR-TB control and can be identified by the prediction model. A kind of vicious circle with a certain delay effect exists between snMDR-TB and MDR-TB. To better control MDR-TB, it is necessary to pay greater attention to snMDR-TB, conduct further research and develop targeted therapeutic strategies.

肺结核患者的MDR-TB知识知晓率调查

目的了解肺结核患者的MDR-TB知识知晓率情况,为有针对性开展健康教育工作提供参考。方法对肺科门诊跟踪治疗管理的肺结核患者进行询问式问卷调查。结果共调查159例肺结核患者,小学及以下学历占67.2%,"什么是MDR-TB"的知晓率为55.9%,"慢性排菌者/初治失败者/复发患者/密切接触MDR-TB患者的涂阳肺结核患者应怀疑得了MDR-TB"的知晓率为13.8%,"产生MDR-TB的原因"的知晓率为26.4%,"如何治疗MDR-TB"的知晓率为15.1%,"MDR-TB能治好吗"的知晓率为30.2%,"如何预防MDR-TB"的知晓率为23.9%。结论肺结核患者的MDR-TB知识知晓率低,应加强MDR-TB的宣传教育。

The Prediction Factors of Pre-XDR and XDR-TB among MDR-TB Patients in Northern Thailand

Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a marker to predict Pre-XDR and XDR-TB is rare. Methods: Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN). Associations between resistant genes and Pre-XDR and XDR-TB in the MDR patients were performed using exact probability tests. Univariable logistic regression was used to quantify the strength of association between the gene mutation with Mycobacterium tuberculosis and the prevalence of Pre-XDR and XDR-TB in the MDR patients. Results: The mutations in the region of the rpoB gene at codon 445 (C445T) in the Pre-XDR or XDR-TB patients were significantly 20.6 times more prevalent among the MDR-TB patients. The inhA gene mutation at codon 114 (T114G) was also significantly 8.1 times more prevalent. Conclusion: The findings can be used to predict the odds of Pre-XDR and XDR-TB in MDR-TB patients, as a guide for prevention and treatments.

Descriptive Epidemiology of Multidrug Resistance Tuberculosis (MDR-TB) in Bangladesh

Background: The number of reported MDR-TB cases has been increasing in recent years. Objectives: To describe the epidemiological profile of MDR-TB cases in Bangladesh. Design: This was a descriptive cross-sectional study. Settings: The study was conducted among the multi drug resistant tuberculosis patient admitted in the National Institute of Diseases of the Chest and Hospital (NIDCH) Dhaka, Bangladesh. Samples: 148 confirmed cases of MDR-TB. Materials and Methods: Hospital admitted MRD-TB cases were randomly chosen from the above mentioned hospital. Semi-structured and pretested questionnaire were introduced by researcher. Clinical and treatment data i.e. duration of TB drug intake, report of sputum, X-ray and blood test etc. were extracted from the hospital record. Results: Study found, majority of the participants (56.1%) were in the age group of 16 - 30 years. 64.2% of the study subjects were married. Majority of the participants education were whether under primary or primary level. 24.3% participant’s family member and 14.5% of neighbor were having TB. Most common comorbidity were diabetes, pulmonary infection, hearing loss, psychiatric symptoms, chest pain, joint pain etc. 63.5% respondent had high degree of AFB for sputum positivity and more than 98% had positive finding in X-ray chest. On an average ESR was low and also few cases of extremely low ESR were found. 71.6% were under twenty four months regimen. Conclusion: We can conclude that, many possible factors for MDR-TB. There is an urgent need for further study to confirm the exact factors in Bangladesh and address those immediately.

Identifying Factors that Affect the Probability of Being Cured from MDR-TB Disease, KwaZulu-Natal, South Africa: A Competing Risks Analysis

Setting: Four decentralised sites are located in rural areas and one centralised hospital in KwaZulu-Natal province, South Africa. Objective: To analyse risk factors associated with multidrug-resistant tuberculosis (MDR-TB) using competing risks analysis. Understanding factors associated with MDR-TB and obtaining valid parameter estimates could help in designing control and intervention strategies to lower TB mortality. Method: A prospective study was performed using a competing risk analysis in patients receiving treatment for MDR-TB. The study focused on 1542 patients (aged 18 years and older) who were diagnosed of MDR-TB between July 2008 and June 2010. Time to cure MDR-TB was used as the dependent variable and time to death was the competing risk event. Results: The Fine-Gray regression model indicated that baseline weight was highly significant with sub-distribution hazard ration (SHR) = 1.02, 95% CI: 1.01 - 1.02. This means that weight gain in a month increased chances of curing MDR-TB by 2%. Results show that lower chances to cure MDR-TB were among patients between 41 to 50 years compared to those patients who were between 18 to 30 years old (SHR = 0.80, 95% CI: 0.61 - 1.06). The chances of curing MDR-TB in female patients were low compared to male patients (SHR = 0.84, 95% CI = 0.68 - 1.03), however this was not significant. Furthermore, HIV negative patients had higher chances to cure MDR-TB (SHR = 1.07, 95% CI: 0.85 - 1.35) compared to HIV positive patients. Patients who were treated in the decentralised sites had lower chances to be cured of MDR-TB (SHR = 0.19, 95% CI: 0.07 - 0.54) as compared to patients who were treated in the centralised hospital. Conclusion: Identifying key factors associated with TB and specifying strategies to prevent them can reduce mortality of patients due to TB disease, hence positive treatment outcomes leading to the goal of reducing or end TB deaths. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant TB.

长治地区MDR-TB流行趋势研究

目的：探讨长治地区ＭＤＲ－ ＴＢ 流行情况。方法：从１９９７ 年１２ 月到１９９８ 年１２ 月对长治地区１２５ 例结核病患者的标本，采用涂片，抗酸染色，分离培养等方法，分离出结核杆菌４２ 株，并通过间接法对４２ 株ＴＢ 菌进行了耐药性测定。结果：阳性分离率３３ ．６ ％ ，１４ 种抗痨药物耐药情况为，无耐药者８ 例，为１９ ．４ ％ ，耐一种药者８ 例，为１９ ．４ ％ ，耐二种药者９ 例，为２１ ．４ ％ ，耐三种药者６ 例，为１４ ．２ ％ ，耐四种药６ 例，为１４ ．２ ％ ，耐５ 种药者４ 例，为９ ．４ ％ ，耐二种以上药２５ 例，为５９ ．５ ％ 。结论：长治地区ＭＤＲ－ＴＢ正在增多，ＭＤＲ－ ＴＢ不断扩散，有可能使目前治疗结核病的化疗方法失去应有的控制作用，对结核病的流行产生严重的影响，因此，将耐药性测定，耐药趋势的追踪和流行病学的分析，作为本地区结核病的流行控制监测的重要手段，应受高度的重视。

二线药治疗耐多药结核病(MDR-TB)应否纳入结核病规划?

21世纪的结核病控制规划问题,例如耐多药结核病(定义为结核菌至少对异烟肼和利福平耐药),需要21世纪的解决方案。传统的结核病政策集中在实行DOTS,通过治愈新病例以预防耐药结核病的出现。当然,提高病例发现率和新病例治愈率将防止它们转为慢性,因而使耐药性降得最低。

母牛分枝杆菌菌苗联合抗结核药在MDR-TB中的应用价值分析

目的对母牛分枝杆菌菌苗联合抗结核药治疗耐多药结核(MDR-TB)的应用价值进行探讨。方法将84例耐多药肺结核患者随机分为观察组和对照组,给予对照组患者常规疗法,给予观察组患者母牛分枝杆菌菌苗联合抗结核药治疗。结果观察组患者的痰菌阴转率、病状吸收情况均优于对照组(P<0.05)。结论治疗MDR-TB采取母牛分枝杆菌菌苗联合抗结核药物,有利于提高痰菌阴转率,加快病灶吸收。

上海市耐多药结核病患者经济负担研究

目的基于上海市近年结核病诊疗费用减免政策,探索耐多药结核病(multidrug resistant tuberculosis,MDR-TB)患者疾病经济负担及其影响因素,为优化MDR-TB诊疗费用减免政策和综合管理模式提供依据。方法收集上海市2017—2019年确诊MDR-TB患者情况和诊疗费用减免情况数据,开展针对疾病经济负担的问卷调查,建立涵盖患者人口和社会经济情况、临床特征、疾病经济负担和诊疗费用减免情况数据库,明确患者疾病经济负担和灾难性卫生支出(catastrophic health expenditure)发生情况。以多元线性回归法分析可能影响患者疾病经济负担的因素,以多因素logistic回归法分析不同比例下灾难性卫生支出发生的影响因素。结果196例纳入研究分析的MDR-TB患者平均年龄为(44±16)岁,男性139例(占70.9%),上海户籍占46.4%,49%的患者为家庭主要劳动力。治疗期间,患者自付诊疗费用中位数为4.0(四分位数区间2.0~6.5)万元。113例患者获得减免诊疗,减免费用中位数为2.6(四分位数区间1.3~4.9)万元。若自付费用占家庭年收入的40%及以上,有47.8%的患者会发生灾难性支出;若不考虑减免政策,有59.8%的患者发生灾难性卫生支出。上海户籍(OR=0.3,95%CI为0.1~1.0)、更低家庭收入水平(P_(trend)=0.002)、医疗保险类型[(农村合作医疗保险/外来人口综合保险(OR=13.3,95%CI为1.0~171.2),无医疗保险(OR=17.5,95%CI为2.7~113.0)]和既往结核病治疗史(OR=3.3,95%CI为1.1~10.0)可能影响灾难性卫生支出的发生。结论上海市MDR-TB患者的自付诊疗费用较高。医疗保障力度较小和家庭经济情况不佳的患者更易发生高额自付费用,导致灾难性卫生支出。上海市MDR-TB诊疗费用减免政策有效降低了患者的经济负担。

35例耐多药结核病临床成因分析与防治对策探讨

据药敏试验观察复治肺结核患者中耐多药结核病(MDR-TB)发生率,循治疗传递进程分析MDR-TB 形成原因,并对符合诊断标准的35例 MDR-TB 患者重新制定方案督导治疗,观察疗效。结果 MDR-TB发生率为57.4%,只治不管、只治不教、治不规范、治不彻底等医源性因素是 MDR-TB 形成的主要原因。治疗9月后,35例患者中,11%死亡,28.6%痰菌转阴,52%X 线病灶显吸或吸收,说明 MDR-TB 治疗困难,死亡率高,应予高度重视。提高医生专业素质、归口管理、督导化疗、强化宣教是防止发生 MDR-TB 的关键。

应用BACTEC MGIT 960分析临床结核菌株耐药性分析

目的研究我院结核病患者的抗结核药物耐药特点。方法我院就医的结核病患者抗结核药物的敏感性试验结果,分析临床抗结核药物的耐药现状。结果 2008～2010年,耐药菌株为4825株(耐药率为66.68%,4825/7236,MDR为1142株,XDR为105株)。XDR-TB比例2008、2009、2010年分别为1.73%(30/1732)、1.33%(34/2548)、1.39%(41/2956)。结论结核病患者的抗结核药物的耐药形势依然严峻,加强抗结核药物的耐药性监测,合理使用药物非常必要。

DNA微阵列芯片技术检测培阳肺结核患者痰样本中结核分枝杆菌耐药性的价值

目的评价DNA微阵列芯片法(以下称芯片法)检测培养阳性患者痰样本的利福平和异烟肼相关耐药基因的效能。方法收集并检测389例疑似肺结核患者痰样,以BACTEC MGIT 960液体药敏(以下称MGIT 960药敏)为参考标准,评价芯片法检测样本利福平(RIF)、异烟肼(INH)耐药性和MDR-TB的灵敏度、特异度及一致性。应用线性探针耐药技术(GenoType MTBDRplus VER 2,0)对不一致的结果进行分析。结果将334例(334/389)MGIT 960培阳结果对应的痰处理液进行芯片法耐药检测,其中2例为非结核分枝杆菌,9例为阴性。与参考标准对比,芯片法对利福平耐药检测的灵敏度为92.4%,特异度为97.7%,Kappa值为0.90;异烟肼为82.6%,特异度为99.2%,Kappa值为0.86。在MDR-TB的病人中,芯片法与MGIT 960药敏法有较好的一致性;且在初治患者中Kappa值为0.95,灵敏度为95.5%,明显优于复治患者。结论线性探针耐药技术对22份不一致结果进行分析,认为检测限及耐药机制的差异、异质性耐药和多重感染等原因是导致基因型和表型或是两种分子法结果不一致的主要原因。应用芯片法检测培阳患者痰样本的利福平和异烟肼的相关耐药基因,与MGIT 960药敏法相比较具有较好的灵敏度、特异度和一致性,可快速检测出患者耐药情况和MDR-TB患者,为临床患者尤其是初治患者提供了快速有效的化疗参考方案。