非耐多药结核治疗过程中耐药性的扩大及其危险因素的分析

发布时间：2018-01-14 19:08

本文关键词：非耐多药结核治疗过程中耐药性的扩大及其危险因素的分析　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:微生物耐药(drug resistance.DR)已成为世界范围内最主要的公共卫生问题之一。尽管全球人民在抗结核的道路上一直都在不懈努力着,并且过去20年结核病在全球范围内发病率及死亡率均有下降趋势。然而,结核病耐药性的逐渐扩大、耐药结核菌株的不断出现已成为结核病控制道路上的又一新绊脚石。自20 世纪 90年代耐多药结核病(Multidrug-resistant tuberculosis,MDR-TB)爆发,至2015年,全球耐多药结核有48万新发结核病患者,其中抗结核治疗成功者仅占48%,年死亡近21万人,耐多药结核病对人类的威胁正逐步加剧。结核病治疗过程中的一个限制性因素就是非耐多药结核病(Non-multi-drug resistant tuberculosis,non-MDR-TB)患者在治疗过程中新出现耐多药结核病,既耐药性在非耐多药结核病患者中的扩大。由于高昂的花费、较差的依从性、治疗周期的延长以及有效抗结核药物的缺乏等因素,耐多药结核病患者的预后往往较药物敏感性结核病患者差。同时,随着结核耐药性的逐渐扩大,广泛耐药结核病(Extensively-drug resistant TB,XDR-TB)甚至全耐药结核病进一步出现。自2006年以来,第一例广泛耐药结核病在全球范围内出现,至2014年,全球有100个国家已经向世界卫生组织(World health organization,WHO)报告过广泛耐药结核病病例,然而据统计其治疗成功率仅占 22%。随着耐药性的逐渐扩大,结核病的治疗失败率也进一步上升,结核患者的生活质量明显降低,社会及经济负担急剧加重。本研究通过对长达8年的结核病细菌培养阳性患者的临床和药物敏感性实验(Drug susceptibility testing,DST)结果进行回顾性分析,目的是了解非耐多药结核病患者在抗结核治疗过程中逐渐扩大的耐药性及评估此类患者中耐药性扩大的相关危险因素,并比较耐药性扩大组同耐药性始终未改变组患者预后的差异。通过这些数据的提醒,希望及早发现结核耐药性扩大的高危人群,加强对此类患者的及时管理,为结核控制策略的制定和调整提供依据,从而在早期阻断结核耐药性的扩大,降低耐多药结核病、广泛耐药结核病甚至全耐药结核病的发病率,改善结核病患者的预后、提高其生活质量。方法:连续收集2007年1月1日至2014年12月31 日山东省胸科医院住院治疗的结核分支杆菌细菌培养阳性且药物敏感性实验结果为非耐多药结核病的患者4932例,除外随访信息不全(后续药物敏感性实验结果丢失等)的患者,最终共计纳入258例非耐多药结核分支杆菌阳性的结核病患者并进行数据统计。分析非耐多药结核病患者在治疗过程中耐药性的扩大现象;分析结核耐药性扩大在该类患者中的危险因素;比较结核耐药性扩大组及药物敏感性实验结果始终未改变组的预后情况。采用SPSS 16.0统计软件进行数据分析,分类资料的组间比较采用卡方检验和Fisher精确概率法;通过单因素分析法比较耐药性扩大组与药物敏感性实验结果始终未改变组之间基本资料的差异;采用多元logistic回归分析方法对耐药性扩大的独立危险因素加以分析。结果:1.最终入选的258例非耐多药结核病患者在治疗过程中,共计38例(14.7%)转变为耐多药结核,19例(14.7%)转变为广泛耐药结核。198例初始全敏感的结核病患者中10例(5.1%)转变为单药耐药,228例初始全敏感或单药耐药结核病患者中12例(5.3%)转变为多药耐药。2.结核耐药性扩大的发生率在多药耐药结核病患者(23/30,76.7%;P0.001)中比单药耐药结核病患者(19/30,63.3%;P0.001)及全敏感结核病患者(56/]98,28.3%)高。3.过量吸烟史(OR,1.74;95%CI.1.04-2.91),既往结核病患者接触史(OR,3.91;95%CI,1.23-12.44),影像学表现为肺部空洞样病变(OR.2.26;95%CI,1.43-3.55)以及因结核病多次入院治疗史(OR,2.34;95%Cl.1.46-3.75)是非耐多药结核病患者耐药性扩大的独立危险因素。4.药物敏感性实验结果始终未改变组预后:60%患者治愈,23.1%失访(lose to follow-up,LFU),6.9%死亡,10%治疗失败。耐药性扩大组预后:39.8%患者治愈或完成治疗,38.8%失访,4.1%死亡,17.3%治疗失败。耐药性扩大组较药物敏感性实验结果始终未变组预后差(60%vs;39.8%p0.005)。结论:结核病患者在正规抗结核治疗过程中耐药性逐渐扩大的现象越来越常见。在非耐多药结核病患者中,耐药性的扩大在抗结核治疗前药物敏感性实验结果表现为多药耐药结核病的患者中较单药耐药结核病患者及全敏感结核病患者高;过量吸烟史、既往结核病患者接触史、影像学表现为肺部空洞样病变以及因结核病多次入院治疗史与结核病患者抗结核治疗过程中耐药性的扩大密切相关;耐药性扩大组较药物敏感性实验结果始终未变组预后差;相关部门可以采取措施积极发现结核病患者中那些存在耐药性扩大的高危人群,通过加强对该部分患者的管理,进一步改善结核病患者的远期预后。
[Abstract]:Background: microbial resistance (drug resistance.DR) has become one of the most important public health problems in the world. Although the global people in anti tuberculosis on the road has been tireless efforts in the past 20 years, and reduced TB worldwide trend of both morbidity and mortality. However, gradually expand the TB drug resistance, constantly the emergence of drug-resistant strains of TB has become another stumbling block on the road since 1990s. The tuberculosis control of multi drug resistant tuberculosis (Multidrug-resistant tuberculosis, MDR-TB) to 2015, the global outbreak of multidrug-resistant tuberculosis 48 million new cases of TB patients, the success of anti tuberculosis treatment accounted for only 48% years, nearly 210 thousand people died, resistance TB drug threat to mankind is gradually increasing. In the process of treatment of tuberculosis is a limiting factor for non multidrug resistant tuberculosis (Non-multi-drug resistant Tuberculosis, non-MDR-TB) with the emergence of new multi drug resistant tuberculosis in the treatment process, both drug resistance in non tuberculosis patients with multi drug resistant expansion in. Because of the high cost, poor compliance, prolonged treatment cycles and the lack of effective anti TB drugs, the prognosis of patients with MDR-TB is drug sensitivity TB patients. At the same time, with the gradual expansion of drug resistance in tuberculosis and extensively drug-resistant tuberculosis (Extensively-drug resistant, TB, XDR-TB) and the drug resistant tuberculosis further. Since 2006, the first cases of extensively drug-resistant tuberculosis worldwide, to 2014, the Global 100 countries have to WHO (World Health Organization, WHO) report after extensively drug-resistant tuberculosis, but according to statistics, the success rate of treatment accounted for only 22%. with drug resistance gradually expanded, the treatment of tuberculosis Treatment failure rate is further increased, the quality of life of patients with tuberculosis was significantly reduced, the social and economic burden increase sharply. Through the study and training of clinical drug sensitivity test positive patients for up to 8 years of tuberculosis (Drug susceptibility testing, DST bacteria) results were retrospectively analyzed. The aim is to understand the non multidrug resistant tuberculosis patients expand gradually in the process of anti tuberculosis treatment of drug resistance and drug resistance in patients with such assessment to expand related risk factors, and compare the resistance group with drug resistance has not changed to expand the group differences in the prognosis of the patients. Through these data to remind, hope early detection of high-risk drug resistant tuberculosis expand, strengthen the timely management of such patients, provide the basis for for the formulation and adjustment of tuberculosis control strategy, in order to expand the TB drug resistance blocking early, reduce multi drug resistant tuberculosis, resistance Drug tuberculosis or even all drug-resistant TB incidence and improve the prognosis of tuberculosis patients and improve their quality of life. Methods: collected from January 1, 2007 to December 31, 2014 in Shandong provincial chest hospital treatment of the bacterial culture positive of Mycobacterium tuberculosis and drug sensitivity test results for 4932 cases of patients with multi drug resistant tuberculosis, incomplete information (except for follow up the following experimental results of drug sensitivity loss) were eventually included in a total of 258 cases of non multidrug resistant Mycobacterium tuberculosis positive TB patients and statistical data. Analysis of multi drug resistant tuberculosis patients during the treatment of drug resistance in the expansion of the phenomenon; analysis of drug resistance in tuberculosis in the patients with increased risk factors; comparison of drug resistant tuberculosis extended group and drug sensitivity test results did not change the prognosis group. Data using statistical software SPSS 16 Analysis of categorical data were compared by chi square test and Fisher exact probability method; the difference has not changed the basic data between the groups by single factor analysis method to compare the resistance of expanded group and drug sensitivity test results; multivariate logistic regression analysis method to analyze independent risk factors for resistance to expand. Results: the final selection of 1. 258 cases of MDR-TB patients in the treatment process, a total of 38 cases (14.7%) into multi drug resistant tuberculosis, 19 cases (14.7%) into.198 cases of extensively drug-resistant tuberculosis sensitive initial full TB patients in 10 cases (5.1%) into a single drug resistance, 228 cases of initial sensitive or single drug resistant tuberculosis patients in 12 cases (5.3%) occurred into multi drug resistant tuberculosis drug resistance.2. expand in multidrug-resistant tuberculosis patients (23/30,76.7%; P0.001) than single drug resistant tuberculosis patients (19/30,63.3%; P0.001 ) and full of TB patients (56/]98,28.3%) and high sensitive.3. excessive smoking history (OR, 1.74; 95%CI.1.04-2.91), previous tuberculosis contact history (OR, 3.91; 95%CI, 1.23-12.44), the imaging manifestations of pulmonary cavitary lesions (OR.2.26; 95%CI, 1.43-3.55) and repeatedly hospitalized due to tuberculosis history (OR, 2.34; 95%Cl.1.46-3.75) is a non multi drug resistant tuberculosis drug resistance to expand the independent risk factors of.4. drug sensitivity test results has not changed: 60% patients were cured, 23.1% lost (lose to follow-up, LFU), 6.9% dead, 10% treatment failure. Patients: 39.8% patients with drug resistance to expand the cure or completion of treatment, 38.8% lost 4.1%, death, 17.3% treatment failures. Drug resistance is always expanding group of drug sensitivity test results were unchanged poor prognosis (60%vs; 39.8%p0.005). Conclusion: the drug resistance of tuberculosis patients gradually expanded in regular anti tuberculosis treatment in the process of the phenomenon More and more common. In multi drug resistant tuberculosis patients, resistance to expand in the anti TB treatment before drug sensitivity test results showed patients than in single drug resistant tuberculosis multi drug resistant tuberculosis patients and patients with high sensitive tuberculosis; excessive smoking history, history of tuberculosis contact history, imaging manifestations of pulmonary cavity due to the expansion of drug resistant tuberculosis lesions and multiple hospital anti tuberculosis treatment history and TB patients during treatment is closely related to drug resistance; extended group is always the results of drug sensitivity experiment has poor prognosis group; the relevant departments to take active measures to find TB patients in those high-risk drug resistance increased, by strengthening the management of some patients. To further improve the long-term prognosis of patients with tuberculosis.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R52

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