MDR- and XDR-TB among suspected drug-resistant TB patients in a tertiary care hospital in India

Aim: To study the anti‐tubercular drug resistance pattern among suspected cases of drug‐resistant TB. Materials and Methods: First and second line drug susceptibility data were retrospectively analysed for all suspected cases of drug‐resistant tuberculosis (TB), presenting to the Pulmonary Medicine department of tertiary care hospital in South India from 2003 to 2007. Results and Discussion: Out of 177 cases of suspected drug‐resistant TB, 103 (58.2%) cases were multi‐drug‐resistant tuberculosis (MDR‐TB). Out of 75 cases of MDR‐TB for whom second‐line drug susceptibility test was performed, 45 (60.0%) cases met the criteria of extensively drug–resistant (XDR) TB, which is very high when compared with existing worldwide data on XDR‐TB (6.6% cases of MDR‐TB). In comparison with non‐MDR‐TB cases, MDR and XDR‐TB cases had a history of significantly higher duration of anti‐TB treatment (ATT) and significantly higher exposure to multiple ATT regimens. Past exposure to second‐line anti‐TB drugs was significantly high in XDR‐TB cases than in MDR‐TB and non MDR‐TB cases. Conclusion: This study highlights the high burden of XDR‐ and MDR‐TB among TB patients coming to tertiary care hospitals in India. Please cite this paper as: James P, Gupta R, Christopher DJ, Thankagunam B and Veeraraghavan B. MDR and XDR‐TB among suspected drug resistant TB patients in a tertiary care hospital in India. Clin Respir J 2011; 5: 19–25.     

Extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR-TB) is defined as Mycobacterium tuberculosis infection that is resistant to isoniazid, rifampin, any fluoroquinolone, and any injectable drug (amynoglicosides or polypetides). Although initially described in South Africa, it has emerged as a global threat, and cases have been reported from several countries, including the United States. XDR-TB has emerged mainly as a consequence of previous inadequate or poorly administered treatment, from failure of the public health infrastructure. As the diagnosis of this condition requires antibiotic susceptibility confirmation, a broad network of reference laboratories and the development of faster and more accurate tests for the identification of active cases of tuberculosis are urgently required. The treatment of XDR-TB is challenging and requires the use of multiple second-line drugs and, potentially, surgery. Infection control measures do not differ from those used for susceptible cases but may require more stringent application.     

含阿米卡星及左氧氟沙星方案治疗耐多药肺结核近期疗效观察

目的　观察和评估含阿米卡星及左氧氟沙星联合化疗方案在耐多药肺结核治疗中的疗效。方法 将 97例耐多药肺结核患者分为治疗组 48例和对照组 49例;化疗方案:治疗组以阿米卡星及左氧氟沙星为主,联合利福喷丁、异烟肼对氨基水杨酸钠、丙硫异烟胺、吡嗪酰胺;对照组用阿米卡星、利副喷丁、异烟肼对氨基水杨酸钠、丙硫异烟胺、吡嗪酰胺,疗程为 21月。结果 共有 93例患者完成化疗疗程。治疗组 46例,痰菌阴转率 87%;对照组 47例,痰菌阴转率 59.6%;痰菌阴转率治疗组明显高于对照组 (P＜0.01).结论 含阿米卡星及左氧氟沙星方案治疗耐多药肺结核有助于痰菌阴转和病变吸收好转,药物不良反应低,值得在临床上推广应用。     

司帕沙星与左氧氟沙星对耐多药肺结核临床疗效

目的 评价新一代氟喹诺酮类药物司帕沙星对耐多药肺结核病(MDR—TB)的治疗作用。方法 将60例MDR-TB患随机平分为两组：治疗组用司帕沙星o．3qd，对照组用左氧氟沙星o．2tid，疗程12月，同时辅以其他抗痨药物治疗。结果 有效率治疗组86．7％，优于对照组80％，痰菌阴转率73．3％，优于对照组70％，两组相比无显差异性(P＞o．05)。结论 司帕沙星是一种有效的抗痨药物。     

Factors affecting outcomes of individualised treatment for drug resistant tuberculosis in an endemic region

BackgroundIndividualised treatment regimens for drug resistant tuberculosis have improved outcomes. This retrospective observational study examined potential factors that affect individualised treatment in an endemic region, and highlighted predictors of a successful outcome.MethodsWe examined records of proven MDR, pre-XDR and XDR TB patients diagnosed and started on treatment between 2010 and 2014, and collected the following data for each patient: age, gender, comorbidities, past history of TB, diagnosis, site of disease, drug susceptibility testing (DST) results, treatment, adverse reactions to anti-tubercular drugs, treatment changes and outcomes, which were recorded as positive, negative or neutral. Tests of association were carried out between factors and outcomes, following which multiple logistic regression analysis was done to determine the predictors of a positive outcome such as patient cured after completion of treatment at 18 months or longer.ResultsFifty-nine patients completed treatment at our centre. The median age was 26 years (range 8–65 years). There were 31 (52.5%) female patients. Forty-four (74.6%) were successfully treated over a median treatment period of 23 months (range 18–30 months). Successful outcomes were associated with age less than 45 years (P = 0.01, OR = 6.67, 95% CI = 1.73–23.47), resistance to fewer than five drugs (P = 0.001, OR = 9.51, 95% CI = 2.50–38.18) and susceptibility to Group 4 drugs (P = 0.04, OR = 4.71, 95% CI = 1.03–16.83).ConclusionsAge and drug susceptibility were important predictors of treatment outcome.     

五药联合方案治疗耐多药结核病的疗效分析

目的　评价异烟肼 (H)、对氨基水杨酸钠 (P)、卷曲霉素 (C)、氧氟沙星 (O)或左氧氟沙星 (L V)和丙硫异烟胺 (Th)方案治疗耐多药结核病 (MDR- TB)的疗效。方法　将 85例 MDR- TB随机分为两组 :治疗组 (4 5例 )应用 H、P、C、O或 L V、Th;对照组 (4 0例 )应用 H、丁胺卡那霉素、利福喷丁、吡嗪酰胺和乙胺丁醇。结果　痰菌阴转率 :治疗组 86 .7% ,对照组 5 5 % ,有高度显著性差异 (P<0 .0 1) ;病灶吸收好转率治疗组 6 4 .4 ,对照组 4 0 ,有显著性差异 (P<0 .0 5 ) ;空洞闭合率 :治疗组 6 8.9 ,对照组 4 0 ,有高度显著性差异 (P<0 .0 1)。随访 2年 ,治疗组和对照组总治愈率分别为 84 .4和 5 0 ,有高度显著性差异 (P<0 .0 1)。结论　 H、P、C、O或 L V、Th方案治疗 MDR- TB疗效满意 ,可作为首选方案     

70例MDR-TB病例抗结核二线药物敏感性检测结果分析

了解耐多药结核分枝杆菌临床分离株对二线药物耐药情况,评价BACTEC MGIT960系统在抗结核二线药敏试验中的临床应用价值。方法 收集本院的痰培养阳性、经菌种鉴定和一线药物的药物敏感性试验确定为耐多药的结核分枝杆菌菌株。采用BACTEC MGIT960对4种二线药氧氟沙星（OFLX）、左氧氟沙星（LVFX）、阿米卡星（AMK）和卷曲霉素（CPM）进行药物敏感性检测,并与改良 L-J罗氏培养法相比较。结果 (1)2008年10月-2009年4月,70例MDR-TB分离到的菌株,包括初治病例26例、复治病例44例,对四种药的总耐药率为61.4%（43/70）。对OFLX、LVFX、AMK和CPM耐药率分别为48.6%、40.0%、17.1%、7.1%。初治耐药率为57.7%（15/26）,复治耐药率达63.6%（28/44）。符合XDR-TB诊断者5例（7.1%）,包括初治者1例（1.4%）,复治者4例（5.7%）。（2）BACTEC MGIT960二线药物敏感试验与改良L-J法相比,平均报告时间仅10.2天,明显短于L-J法,符合率在90%以上。结论 （1） 在住院耐多药结核病患者中对这四种抗结核二线药物的耐药率已经到了一个较高水平;同时,当地存在XDR-TB,应该引起重视。（2）BACTEC MGIT960系统可以准确而快速地检测结核分枝杆菌对二线药物的耐受性.     

Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District

BackgroundTreatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes.MethodsThis is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed.ResultsThe treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin.ConclusionTo reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes.     

应用结核病DNA疫苗治疗小鼠耐多药结核病的研究

目的 研究结核分枝杆菌Ag85A质粒DNA疫苗单独或联合药物治疗小鼠耐多药结核病的效果,为建立耐多药结核病的免疫治疗新策略和新方案奠定基础.方法 用结核分枝杆菌高耐利福平、低耐异烟肼临床分离株HB361尾静脉注射17～19 g的6～8周龄雌性BALB/C小鼠后,将小鼠随机分为6组,每组10只.感染后第2天开始,分别用pVAX1载体(A组)、利福平(B组)、吡嗪酰胺(C组)、Ag85A质粒DNA疫苗(D组)、Ag85A质粒DNA疫苗联合利福平(E组)、Ag85A质粒DNA疫苗联合吡嗪酰胺(F组)治疗60 d.治疗结束后4周,分别取肺、肝和脾观察病理改变,称取重量,做菌落计数.结果 小鼠感染4周后,肺内菌量达到1.5×107 CFU,脾内菌量达到1.1×106 CFU.A、B组小鼠死亡率均为10%,其余各组小鼠均存活.治疗结束后4周,肺组织病理显示,各治疗组肺组织病变均有不同程度减轻,病变局限,可见正常的肺泡结构,肺泡轮廓相对清晰.与A组比较,C、D、E、F组肺组织菌落数分别减少了1.18、1.35、1.38、1.08 logs,脾脏菌落数分别减少了0.91、1.00、1.26、1.03 logs(P＜0.01).结论 结核分枝杆菌Ag85A质粒DNA疫苗单独或联合药物治疗小鼠耐多药结核病均有显著疗效.Ag85A质粒DNA疫苗与抗结核药物联合治疗是治疗耐多药结核病的最有前途的免疫策略.     

耐多药结核病的分子机制研究进展

耐药结核病尤其耐多药结核病的发生和流行是当前结核病疫情回升的主要原因之一,成为结核病控制的重要障碍.本文从耐多药结核病的发展现状出发,归纳了各种耐单药结核病、耐多药结核病已有的分子机制研究,从耐多药结核病发病治疗现状、分子生物学、耐多药检测技术角度指出了目前国内外耐多药结核病已有的分子机制研究成果,在此基础上对耐多药结核病发病的分子机制规律的研究前景予以了展望.     

耐多药肺结核患者肾上腺皮质水平的临床研究

目的　探讨耐多药肺结核患者肾上腺皮质水平的变化规律。方法 采用放射免疫分析法对56例耐多药肺结核患者进行血清皮质醇含量测定,并与无耐药肺结核、正常健康人进行对比。结果 耐多药肺结核患者的皮质醇含量分别为842±168(8AM)、624±62(4PM),均明显高于非耐药肺结核组和正常组。结论 耐多药肺结核患者肾上腺皮质功能较正常人明显增加,且皮质醇分泌仍具有正常节律性。     

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive,rifampicin-resistant and multi-drug resistant tuberculosis patients: a computerized tomography study with history length matched cases

BackgroundThere have been concerns that literature described radiological feature differences between drug-sensitive pulmonary tuberculosis (DS-PTB) and multidrug-resistant (MDR)-PTB were confounded by that MDR-PTB cases tend to have a longer history. Using history length matched DS-PTB and MDR-PTB cases from a well-defined urban region in Dalian, we retrospectively analysed the CT feature differences of these paired cases with a focus on pulmonary nodular (PN) consolidation and pulmonary cavity (PC).MethodsThere were 33 consecutive MDR-PTB cases [inclusive of rifampicin-resistant (RR) cases, 27 males and 6 females, mean age: 49.2 years], with 19 cases had a history of <1 month and 8 and 6 cases had a history of 1–6 and >6 months respectively. To pair the MDR-PTB cases with history length, matched 33 cases of DS-PTB patients (21 males and 12 females, mean age: 56.5 years) were included. All patients were new PTB without HIV infection. The first CT exams prior to treatment were analysed.ResultsCompared with DS cases, MDR cases had a much higher prevalence of PN (75.76% vs. 45.45%) and a higher number of PN per positive case for PN (6.2 vs.1.53). For the cases >1 month history, MDR-PTB had a higher number of PC per positive case than that of DS-PTB cases (7.18 vs. 2.36). To differentiate DS-PTB from MDR-PTB, receiver operating characteristic (ROC) analysis showed a cutoff PN number of ≥3 had 48.5% sensitivity and 93.9% specificity, and a cutoff PC number of ≥4 had 39.4% sensitivity and 84.9% specificity. The lung field distribution of all lesions tended to be wider for MDR-PTB cases. MDR-PTB cases appeared to be associated with a faster progression in the absence of treatment.ConclusionsMDR-TB is likely intrinsically more invasive than DS-TB. Multiple PN and Multiple PC are promising signs for the suspicion of MDR-PTB on chest imaging.     

老年肺结核的临床特点

通过对５９２例老年肺结核临床资料的分析，并与同期２１０例中青年肺结核相比较，总结老年肺结核的特点为：（１）临床症状复杂而不典型，除有咳嗽、咳痰、发热、咯血等常见肺结核症状外，也常有以乏力、食欲不振、消瘦、精神萎糜、呼吸困难等症状中之１－２项为主要表现或首发症状者；（２）合并症明显多于对照组；（３）Ｘ线表现多样，以双侧病变、浸润型和慢性纤维空洞型改变为多见；（４）误诊率高；（５）治疗难，初治、复治有     

HIV and tuberculosis co-infection in south-western Sydney: experience from a case series

A case series of six patients with HIV and Mycobacterium tuberculosis co-infection is presented. All patients were overseas-born and in all but one there was profound immunodeficiency. We recommend HIV screening of all cases of M. tuberculosis and a high degree of suspicion of tuberculosis in immigrants with HIV infection from endemic areas. Management problems included delayed diagnosis, rapid progression, paradoxical reactions and requirement for surgical intervention in three patients. Therapeutic complications included possible drug malabsorption, adverse events and drug interactions. M. tuberculosis was fully drug sensitive in all cases.     

莫西沙星和奈替米星联合方案治疗耐多药肺结核的近期疗效观察

目的评价含莫西沙星和奈替米星联合化疗方案对耐多药肺结核(MDR-PTB)的疗效。方法将56例MDR-PTB患者随机分为两组,治疗组28例采用以莫西沙星(M)和奈替米星(N)为主,联合力克肺疾(D)、丙硫异烟胺(Pt)、吡嗪酰胺(Z);对照组28例采用以左氧氟沙星(V)和阿米卡星(A)为主,联合D、Pt、Z;疗程均为21个月。结果:治疗组痰菌阴转率92.9%,对照组痰菌阴转率67.9%,治疗组明显高于对照组(P<0.05)。结论含莫西沙星和奈替米星方案治疗耐多药肺结核有助于痰菌阴转和病灶吸收,药物不良反应低,值得在临床推广应用。