含安美汀方案治疗耐多药结核病的近期疗效初步观察

目的 对多耐工（ＭＤＲ）肺结核产生机理及应用二线结核药治疗方案进行探讨。并阐明安美汀作用机制。方法 采用中国防迸协会制定的结核分枝杆菌多耐药标准及疗效判定对我院１０年来７２例多耐药肺结核，应用抗结核二线药（对照组）与含安美汀抗结核二线药方案（治疗组）进行比较。结果 对７２例多耐药肺结核病例进行分析，治疗组与对照组６个月胸片好转率及痰菌阴转率相比有显著差异（Ｐ〈０．０５）。结论 安美汀是一种新的、有     

1996—2006年南京地区结核病耐药状况分析

目的　了解南京地区近年来结核病耐药的发展趋势。方法 对1996—2006年南京市胸科医院肺结核病例采用绝对浓度间接法进行了10种常用抗结核药物的敏感试验并对结果进行分析。结果 各年每种抗结核药物的耐药率在一定范围内上下波动,但是耐多药率却是呈现逐步上升趋势,一线抗结核药物的耐药率明显高于二线抗结核药物的耐药率。结论 耐多药的发展趋势对目前以INH和RFP为主要抗结核药物的治疗方案构成了巨大的威胁,尽快开发新的低毒高效的抗结核药物是解决目前抗结核治疗困境的当务之急。     

含结核清和含对氨基水杨酸钠方案治疗耐多药肺结核疗效分析

目的　考核结核清抗结核的疗效并寻求治疗耐多药肺结核合理有效的方法。方法 选取39例耐多药肺结核患者,随机分为含结核清(DPC)组及含对氨基水杨酸钠(P)组。结果 两组方案满疗程后痰菌阴转率分别为95%、93%。X线胸片吸收好转率均为86%。随访二年复发率分别为5%、8%。以上两组结果比较差异均无显著性(P>0.05)。但P费用比DPC高数倍且含DPC组胃肠道反应及静脉炎发生率远低于含P组(P<0.05)。结论 DPC、P分别配合K、O、TH、Z组成的治疗耐多药肺结核方案安全有效,适用于耐多药结核的治疗,含DPC组的2 KOTHZ DPC/6-10 OTHZ DPC方案口服给药、费用较含P组低、副作用小患者易接受,值得推广。     

含阿莫西林／克拉维酸方案治疗耐多药结核病的初期临床观察

目的：观察和评价阿莫西林／克拉维酸在耐多药肺结核治疗中的疗效及安全性。方法：采用中国防痨协会制定结核分支杆菌耐多药标准及疗效判定,对我院10年来72例耐多药肺结核病人随机分成2组,应用抗结核二线药（对照组30例）与含阿莫西林／克拉维酸抗结核二线药方案（治疗组40例）进行比较。结果：治疗组与对照组经6个月治疗,胸片好转率及痰菌阴转率,有效率均有显著性差异（P值＜0．05）。结论：含阿莫西林／克拉维酸治疗方案适合于耐药肺结核应用。     

肺结核球中结核菌药敏实验结果的临床意义

目的　通过研究肺结核球中结核菌的培养和药敏来指导肺结核球的临床治疗。方法 采用手术切除肺结核球后对其中的结核菌做培养和药敏实验。结果 除异烟肼外肺结核球中结核菌对其他抗结核药物的敏感性均在81.4%以上 ,结核菌对抗结核药物组合后的敏感性亦满意。结论 绝大部分肺结核球的治疗不一定需要采用耐药和耐多药方案 ,手术后仍可采用 2HRZS/4HRZ方案治疗且效果满意。     

常住人口与外来人口肺结核病人耐药性分析

目的　为了解门诊病人中常住人口与外来人口 (以下简称“不同人口”)肺结核病人耐药性的异同。方法 采用绝对浓度间接法,应用改良罗氏培养基对分离菌株进行抗结核药耐药性测定。对不同人口肺结核耐药病例分初、复治两组进行分析。结果 不同人口肺结核病人对常用抗结核药耐药率差别不大,复治病例耐药率明显高于初治病例。两者的初治病例均以耐单药为主、复治病例以耐多药为主。外来人口男、女肺结核病人耐药率均高于常住人口,且外来人口耐药病例比常住人口更年青化。结论 常住人口及外来人口肺结核均处于高耐药状态,须加强结核病耐药性监测。外来人口男、女复治肺结核病患者耐药率都比常住人口高,应引起注意。     

127株结核分枝杆菌基因分型及耐药相关研究

目的 研究山西省长治及周边地区结核分枝杆菌的基因多态性及基因型与耐药的相关性。方法 收集结核分枝杆菌临床分离株,运用MLVA方法进行基因分型,对8种抗结核药物分别采用比例法进行药敏试验,应用 BioNumerics 5.0软件进行聚类分析。结果 15个位点中Mtub21、MIRU26和ETRE多态性较高 (HGI>0.6),MIRU40、ETRB、MIRU16、ETRD、MIRU23和ETRC位点多态性较低(HGI＜0.3)。127株结核分枝杆菌共分为11个基因群102种基因型,90 株为独特型,基因群中Ⅰ群所占比例最大(80.31%)。127株菌株对一线和二线抗结核药物的总耐药率分别为47.24%和23.62%。一线药物中链霉素(40.94%)的耐药率最高,乙胺丁醇(6.30%)最低。二线药物中左氧氟沙星(14.17%)的耐药率最高,丙硫异烟胺(3.15%)最低。链霉素的单耐药率最高(11.81%);耐多药率为21.26%(27/127);广泛耐多药率为3.15%。Ⅰ群菌株的耐药率与其它菌株的差别无统计学意义。结论 初步证实山西长治及周边地区的结核分枝杆菌具有明显的多态性,Ⅰ群为主要流行群。结核分枝杆菌对二线药物的敏感性高于一线药物。主要流行菌株Ⅰ群菌株与耐药无明显的相关性。     

耐多药空洞肺结核的介入治疗

目的　探讨耐多药空洞肺结核介入治疗的意义。方法 采用 36例临床培养的耐药菌株作耐药结核菌抑制试验、临床对照观察的方法。 1 80例耐多药空洞肺结核住院患者随机分成两组,均用 3DLOZA/1 8DLOZ化疗方案治疗,治疗组 86例配合抗结核药物凝胶介入治疗并完成疗程。结果 提高抗结核药物浓度,可有效控制耐药结核菌生长,而所需浓度远远低于药物凝胶的含药浓度。临床观察治疗组比对照组痰菌阴转率高 (88.4%),痰菌阴转速度也快,空洞闭合率高 (43.0%),空洞闭合速度快,疗效较好。单发空洞、干酪空洞的疗效比多发空洞、纤维空洞的疗效较好。未发现与介入药物凝胶有关的不良反应。结论 经纤支镜引导灌注抗结核药物凝胶,是治疗耐多药空洞肺结核的有效方法,其有净化空洞,促使痰菌转阴,空洞闭合的作用。并且有安全无创,无明显不良反应,并发症少的优点,值得临床推广使用。     

西利宾胺预防抗结核药物肝损害的临床观察

目的　探讨西利宾胺对初治菌阳肺结核患者抗结核药物肝损害的预防效果。方法 242例初治菌阳肺结核分为观察组和对照组,均应用“2HRZS(E)/4HR”方案抗结核化疗,观察组加用西利宾胺,对照组加肝泰乐。结果 观察组药物性肝损害发生率为6.6%;中断抗结核化疗为41%;调整化疗方案为16%;与对照组的19.2%、14.2%、9.2%比较,均有显著性差异(P<0.01)。结论 西利宾胺可显著降低初治菌阳肺结核患者抗结核药物肝损害的发生率,减少因抗结核药所致肝损害而造成的不规则化疗。     

深圳市耐多药结核病人管治效果初步评价

目的分析深圳市耐多药肺结核的诊断、治疗、管理及其效果,并为制定耐多药肺结核病防治对策提供参考依据。方法政府提供专项经费;确保结核分枝杆菌实验室的质量保障;确保一、二线抗结核药物的供应; DOT管理的患者接受免费的一、二线抗结核药物、治疗监测和DOT管理服务;全程管理服务的患者接受免费的治疗监测。结果2003—2006年,共有111例接受治疗,出现不良反应率60.4%,治疗成功率59.5%,丢失率18.9%,失败率11.7%; 48例耐多药肺结核病人接受DOT免费管理,治愈34例,治愈率70.8%。63例耐多药肺结核病人接受自费的全程管理,治愈22例,治愈率34.9%。 结论逐步推行DOTS-plus策略,可提高耐多药肺结核的治愈率,减少耐药结核的传播。     

含左氧氟沙星方案治疗耐多药肺结核近期疗效观察

目的观察含左氧氟沙星联合化疗方案在耐多药肺结核（MDR—TB）治疗中的疗效。方法将我院收治62例耐多药肺结核患者随机分为治疗组31例，对照组31例。治疗组患者给予左氧氟沙星联合异烟肼对氨基水杨酸钠、利福喷汀、乙胺丁醇、吡嗪酰胺。对照组用链霉素，异烟肼对氨基水杨酸钠、利福喷汀、乙胺丁醇、吡嗪酰胺，疗程均为18个月。结果两组患者6个月时痰菌阴转率间差异有非常显著性意义（P〈0．01）；两组患者病灶吸收情况间差异有显著性意义（P〈0．05）；两组患者药物不良反应发生率间差异无显著性意义（P〉O．05）。结论含左氧氟沙星的联合化疗方案治疗耐多药性肺结核，有助于痰菌阴转率和病灶显著吸收好转率，药物不良反应低，值得推广使用。     

Management of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis: current status and future prospects

Resistance in Mycobacterium tuberculosis arises from man-made selection of genetic mutants that result from spontaneous chromosomal alterations. Thus, drug-resistant tuberculosis (TB) is generally due to inappropriate treatment regimen, poor drug quality, erratic drug supply and poor patient adherence to treatment, reflecting failure in the implementation of an effective TB control programme. Multidrug-resistant TB (MDR-TB) usually denotes bacillary resistance to at least isoniazid and rifampicin. Proper implementation of the directly observed treatment, short-course (DOTS) strategy should achieve a high cure rate for disease and curtail the development of drug resistance. Innovations in reinforcement of this strategy should further facilitate its delivery and enhance its effectiveness. However, established MDR-TB is notoriously difficult to treat, and necessitates the use of alternative specific antituberculosis chemotherapy regimens. These regimens comprise combination use of second-line antituberculosis drugs, that are generally more costly and toxic, and have to be given for longer durations. The fluoroquinolones, better tolerated by patients, have a pivotal role in MDR-TB treatment. Optimal delivery of these treatment regimens mandates a programmatic basis which is now included under the Stop-TB Drug-Resistance Programme(s). The key components embrace political commitment, quality-assured drug susceptibility testing, reliable supply of quality drugs, delivery of chemotherapy under directly observed settings, and a sound recording and reporting system to monitor the individual treatment outcome of patient and overall performance of the TB control programme. Adjunctive surgery in selected MDR-TB patients help to improve their treatment success. Further exploration is required regarding the use of immunotherapy. The recent emergence of extensively drug-resistant TB (XDR-TB), representing MDR-TB with additional bacillary resistance to fluoroquinlones and one or more of the second-line injectable drugs -kanamycin, amikacin and capreomycin, threatens the global control of TB. Given the escalating size of the problem of MDR-TB and XDR-TB worldwide, gigantic instillation of resources is required for control of this formidable challenge, largely through more accurate and rapid drug susceptibility testing (especially for rifampicin and fluoroquinolone), regular drug-resistance surveillance, development of new antituberculosis drugs and other therapeutic modalities, intensive infection control, especially in HIV care settings, as well as strengthening of currently functioning DOTS and Drug-Resistance Programmes.     

含左氧氟沙星及卷曲霉素方案治疗耐多药肺结核近期疗效分析

目的　观察和评价含左氧氟沙星和卷曲霉素联合化疗方案在耐多药肺结核 (MDR PTB)治疗中的疗效。方法　将 177例MDR PTB患者分为治疗组 88例和对照组 89例。化疗方案 :治疗组以左氧氟沙星和卷曲霉素为主 ,联合利福喷汀、异烟肼、对氨基水杨酸钠、吡嗪酰胺 ;对照组用链霉素、乙胺丁醇 ,联用药物同治疗组 ,疗程均为 2 1个月。结果　共有 16 1例患者完成化疗疗程 ,治疗组 82例 ,痰菌阴转率 83% ;对照组 79例 ,痰菌阴转率 5 8% ;痰菌阴转率治疗组明显高于对照组 (P <0 0 1) ;治疗组病灶显效率 5 0 % ,空洞闭合率 6 3% ,治疗组优于对照组 (P <0 0 1) ;治疗组的药物不良反应率为 31% ,对照组为 35 % ,两组比较差异无显著性 (P >0 0 5 )。结论　含左氧氟沙星和卷曲霉素的方案治疗MDR PTB ,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     

左氧氟沙星及力克菲蒺治疗耐多药肺结核病的疗效观察

目的观察含左氧氟沙星和力克菲蒺的化疗方案在治疗耐多药肺结核病的疗效。方法将98例耐多药肺结核分为治疗组50例和对照组48例,治疗组以左氧氟沙星和力克菲蒺为主,联合丁胺卡那霉素、利福喷丁、丙硫异烟胺;对照组用丁胺卡那霉素、利福喷丁、丙硫异烟胺、吡嗪酰胺及乙胺丁醇,疗程均为21个月。结果疗程结束后,治疗组痰菌阴转率、空洞闭合率及病灶吸收好转率分别为82%、77.5%及84%,对照组则分别为56.3%、54.3%及52.1%,两组比较差异显著(分别为P<0.01,P<0.05及P<0.005);两组的不良反应分别为30%及27.1%,差异无显著性(P>0.05)。结论含左氧氟沙星及力克菲蒺的方案治疗耐多药肺结核安全有效,值得推广应用。     

Multidrug and extensively drug-resistant TB (M/XDR-TB): problems and solutions

Multi Drug Resistant Tuberculosis (MDR-TB) and Extensively Drug Resistant Tuberculosis (XDR-TB) are posing a threat to the control of tuberculosis. The first WHO-IUATLD antituberculosis drug resistance surveillance carried out in 1994 in 35 countries reported the median prevalence of primary and acquired multi drug resistance as 1.4% and 13% respectively. Subsequently, second, third and fourth WHO-IUATLD global drug resistance surveillances were carried out in 1996-99, 1999-2002 and 2002-2007 respectively. Based on drug resistance information from 114 countries, the proportion of MDR-TB among all cases was estimated for countries with no survey information. It was estimated that 4,89,139 cases of MDR-TB emerged in 2006. China and India carry approximately 50% of the global burden. 35 countries and two Special Administrative Regions (SARs) reported data on XDR-TB for the first time in 2006. Multidrug and extensively drug-resistant TB 2010 Global report on Surveillance and response estimated that 4,40,000 cases of MDR-TB emerged globally in 2008 and caused an estimated 1,50,000 deaths. 5.4% of MDR-TB cases were found to have XDR-TB. To date, a cumulative total of 58 countries have confirmed at least one case of XDR-TB. M/XDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective use of first line drugs in every new patient. The DOTS Plus proposed by WHO highlights the comprehensive management strategy to control MDR-TB. Laboratory services for adequate and timely diagnosis of M/XDR-TB must be strengthened and programmatic management of M/XDR-TB must be scaled up as per target set by global plan. Proper use of second-line drugs must be ensured to cure existing MDR-TB, to reduce its transmission and to prevent XDR-TB. Sound infection control measures to avoid further transmission of M/XDR-TB and research towards development of new diagnostics, drugs and vaccines should be promoted to control M/XDR-TB.     

The 5-year outcome of multidrug resistant tuberculosis patients in the Cape Province of South Africa

Little is known about the outcome of multidrug resistant (MDR) tuberculosis (TB) in developing countries. In this study, 443 patients with MDR-TB, defined as resistance to two or more antituberculosis drugs, were identified over the 2-year period 1987 and 1988 in the Cape Province of South Africa. The 5-year outcome of the 343 (77%) patients that could be traced by questionnaire was evaluated retrospectively during 1992 and 1993. Of these, 240 (70%) were resistant to both isoniazid (H) and rifampicin (R) with or without resistance to other first-line antituberculosis drugs and 103 (30%) were resistant to H or R and/or other antituberculosis drugs. Mortality was 116 (48%) and 28 (27%) in these groups respectively with a significantly greater risk of death in the first group. Only 114 (33%) of all the MDR-TB patients were cured after 5 years, 50 (15%) were respiratory disabled and 44 (13%) were still bacteriology positive. Twenty-four (7%) patients were lost during follow-up. Taking into account the high costs involved in treating MDR-TB patients and the scarce resources available in developing countries, more emphasis should be placed on direct observed therapy to cure newly diagnosed infectious drug sensitive tuberculosis patients, thus preventing MDR-TB rather than treating it.     

Outcome of multi-drug-resistant tuberculosis in France: a nationwide case-control study.

The factors related to the outcome of 51 cases of multi-drug-resistant tuberculosis (MDR-TB) reported in 1994 to the French National Reference Center were retrospectively analyzed. The patients (median age, 45 yr) were mainly male (75%), foreign-born (63%), and had pulmonary involvement (95%). Sixteen percent were human immunodeficiency virus (HIV)-coinfected. The number of drugs to which the Mycobacterium tuberculosis isolates were susceptible was four. Only 82% of the patients have been hospitalized at any time (median duration, 33 d). Five patients (9%) received no antituberculosis drugs, although three had drug susceptibility results, indicating that two or more active drugs were available; 46 (91%) received drugs, including 37 who received two or more active drugs. Among the nine cases who received only one active drug, three had drug susceptibility results, indicating that two or more active drugs were available. By December 1996, 10 patients were lost before treatment completion, 24 had treatment failure, and 17 had a favorable outcome. The median survival time was 31 mo. Factors related to a poorer outcome were HIV-coinfection (hazard ratio [HR] = 41), treatment with less than two active drugs (HR = 9.9), and MDR status knowledge at the time of diagnosis (HR = 3.3). The country of birth was not associated with a poorer outcome. The management and outcome of MDR-TB in France has to be improved. A solution would be to develop a specialized unit or team for the treatment of MDR-TB, as recommended by the World Health Organization (WHO).     

Management of multi-drug resistant tuberculosis: practitioner's view point

Multi-Drug Resistant Tuberculosis (MDR-TB) is a growing hazard to human health world wide and threat to control of tuberculosis. Current estimates report the prevalence of primary and acquired MDR-TB in India as 3.4% and 25% respectively. MDR-TB is suspected if sputum is persistently +ve for AFB along with clinical and radiological deterioration after multiple courses of irregular or regular treatment including 4 months of WHO retreatmant regimens under direct observation . Diagnosis is confirmed by drug susceptibility testing from reliable and reputed laboratories under constant quality control. Reports of susceptibility should not be accepted uncritically. Treatment of MDR-TB should be at a specialized centre with standard microbiology laboratory facilities. Though treatment guidelines including standardized, empirical and individualized approaches have been laid down by the WHO but therapy should be tailored to the needs of the particular patient. Treatment of MDR-TB is difficult, complicated, much costlier, challenging and needs experience and skills. All measures should be taken to persuade and encourage patients not to stop treatment despite all its discomforts to prevent morbidity, mortality and transmission of MDR-TB. Current proposal of DOTS Plus by WHO highlights the comprehensive management strategy to control MDR-TB. MDR-TB is a man-made problem and its emergence can be prevented by prompt diagnosis and effective treatment of all TB cases. Adoption of directly observed treatment short course (DOTS) to prevent the resistant/multi-drug resistant strains and careful introduction of second line drugs to treat patients with MDR-TB are the top priorities for the proper control of MDR-TB.     

黑龙江省耐多药与非耐多药肺结核患者在DOTS策略下远期治疗效果分析

目的 分析在DOTS策略下使用一线抗结核药治疗的耐多药与非耐多药肺结核患者成功治疗后的远期治疗效果。 方法 采用回顾性队列研究方法,随访2004年黑龙江省耐药监测期间确诊并成功治疗的耐多药肺结核（MDR-TB）患者（暴露组,随访194例患者,访视到111例）及按1：1比例为存活MDR-TB患者配对的非MDR-TB患者(对照组,选择并访视患者71例,其中对所有药物均敏感41例,耐多药以外耐药30例),观察其4年来复发情况,分析存活病例中耐多药（71例）与非耐多药（敏感41例,耐多药以外耐药30例）、治疗分类（初治80例,复治62例）及治疗方案（规划方案124例,科研方案18例）对患者成功治疗后4年复发情况的影响。 结果 暴露组,4年复发率为46.85%（52/111）。在暴露组患者中死亡40例,4年复发率为67.50%(27/40);存活71例,4年复发率为35.21%（25/71）。对照组71例,复发17例,4年复发率为23.94%（17/71）。存活MDR-TB的复发风险高于对一线抗结核药完全敏感患者（χ²=4.19,P=0.041;RR=2.06,95% CI：0.98～4.34)。复治患者的复发率（40.32%,25/62）高于初治（21.25%,17/80）（χ²=6.10,P=0.014;RR=1.90,95%CI：1.13～3.19)。采用规划方案、科研方案患者的4年复发率分别为29.84%（37/124）和27.78%（5/18）,两者间差异无统计学意义（χ²=0.02,P=0.894)。结论 对MDR-TB患者采用DOTS策略治疗成功后的4年复发率高,复治患者复发风险高于初治。