本文關(guān)鍵詞：非耐多藥結(jié)核治療過程中耐藥性的擴大及其危險因素的分析　出處：《山東大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

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【摘要】：背景:微生物耐藥(drug resistance.DR)已成為世界范圍內(nèi)最主要的公共衛(wèi)生問題之一。盡管全球人民在抗結(jié)核的道路上一直都在不懈努力著,并且過去20年結(jié)核病在全球范圍內(nèi)發(fā)病率及死亡率均有下降趨勢。然而,結(jié)核病耐藥性的逐漸擴大、耐藥結(jié)核菌株的不斷出現(xiàn)已成為結(jié)核病控制道路上的又一新絆腳石。自20 世紀 90年代耐多藥結(jié)核病(Multidrug-resistant tuberculosis,MDR-TB)爆發(fā),至2015年,全球耐多藥結(jié)核有48萬新發(fā)結(jié)核病患者,其中抗結(jié)核治療成功者僅占48%,年死亡近21萬人,耐多藥結(jié)核病對人類的威脅正逐步加劇。結(jié)核病治療過程中的一個限制性因素就是非耐多藥結(jié)核病(Non-multi-drug resistant tuberculosis,non-MDR-TB)患者在治療過程中新出現(xiàn)耐多藥結(jié)核病,既耐藥性在非耐多藥結(jié)核病患者中的擴大。由于高昂的花費、較差的依從性、治療周期的延長以及有效抗結(jié)核藥物的缺乏等因素,耐多藥結(jié)核病患者的預(yù)后往往較藥物敏感性結(jié)核病患者差。同時,隨著結(jié)核耐藥性的逐漸擴大,廣泛耐藥結(jié)核病(Extensively-drug resistant TB,XDR-TB)甚至全耐藥結(jié)核病進一步出現(xiàn)。自2006年以來,第一例廣泛耐藥結(jié)核病在全球范圍內(nèi)出現(xiàn),至2014年,全球有100個國家已經(jīng)向世界衛(wèi)生組織(World health organization,WHO)報告過廣泛耐藥結(jié)核病病例,然而據(jù)統(tǒng)計其治療成功率僅占 22%。隨著耐藥性的逐漸擴大,結(jié)核病的治療失敗率也進一步上升,結(jié)核患者的生活質(zhì)量明顯降低,社會及經(jīng)濟負擔急劇加重。本研究通過對長達8年的結(jié)核病細菌培養(yǎng)陽性患者的臨床和藥物敏感性實驗(Drug susceptibility testing,DST)結(jié)果進行回顧性分析,目的是了解非耐多藥結(jié)核病患者在抗結(jié)核治療過程中逐漸擴大的耐藥性及評估此類患者中耐藥性擴大的相關(guān)危險因素,并比較耐藥性擴大組同耐藥性始終未改變組患者預(yù)后的差異。通過這些數(shù)據(jù)的提醒,希望及早發(fā)現(xiàn)結(jié)核耐藥性擴大的高危人群,加強對此類患者的及時管理,為結(jié)核控制策略的制定和調(diào)整提供依據(jù),從而在早期阻斷結(jié)核耐藥性的擴大,降低耐多藥結(jié)核病、廣泛耐藥結(jié)核病甚至全耐藥結(jié)核病的發(fā)病率,改善結(jié)核病患者的預(yù)后、提高其生活質(zhì)量。方法:連續(xù)收集2007年1月1日至2014年12月31 日山東省胸科醫(yī)院住院治療的結(jié)核分支桿菌細菌培養(yǎng)陽性且藥物敏感性實驗結(jié)果為非耐多藥結(jié)核病的患者4932例,除外隨訪信息不全(后續(xù)藥物敏感性實驗結(jié)果丟失等)的患者,最終共計納入258例非耐多藥結(jié)核分支桿菌陽性的結(jié)核病患者并進行數(shù)據(jù)統(tǒng)計。分析非耐多藥結(jié)核病患者在治療過程中耐藥性的擴大現(xiàn)象;分析結(jié)核耐藥性擴大在該類患者中的危險因素;比較結(jié)核耐藥性擴大組及藥物敏感性實驗結(jié)果始終未改變組的預(yù)后情況。采用SPSS 16.0統(tǒng)計軟件進行數(shù)據(jù)分析,分類資料的組間比較采用卡方檢驗和Fisher精確概率法;通過單因素分析法比較耐藥性擴大組與藥物敏感性實驗結(jié)果始終未改變組之間基本資料的差異;采用多元logistic回歸分析方法對耐藥性擴大的獨立危險因素加以分析。結(jié)果:1.最終入選的258例非耐多藥結(jié)核病患者在治療過程中,共計38例(14.7%)轉(zhuǎn)變?yōu)槟投嗨幗Y(jié)核,19例(14.7%)轉(zhuǎn)變?yōu)閺V泛耐藥結(jié)核。198例初始全敏感的結(jié)核病患者中10例(5.1%)轉(zhuǎn)變?yōu)閱嗡幠退?228例初始全敏感或單藥耐藥結(jié)核病患者中12例(5.3%)轉(zhuǎn)變?yōu)槎嗨幠退帯?.結(jié)核耐藥性擴大的發(fā)生率在多藥耐藥結(jié)核病患者(23/30,76.7%;P0.001)中比單藥耐藥結(jié)核病患者(19/30,63.3%;P0.001)及全敏感結(jié)核病患者(56/]98,28.3%)高。3.過量吸煙史(OR,1.74;95%CI.1.04-2.91),既往結(jié)核病患者接觸史(OR,3.91;95%CI,1.23-12.44),影像學(xué)表現(xiàn)為肺部空洞樣病變(OR.2.26;95%CI,1.43-3.55)以及因結(jié)核病多次入院治療史(OR,2.34;95%Cl.1.46-3.75)是非耐多藥結(jié)核病患者耐藥性擴大的獨立危險因素。4.藥物敏感性實驗結(jié)果始終未改變組預(yù)后:60%患者治愈,23.1%失訪(lose to follow-up,LFU),6.9%死亡,10%治療失敗。耐藥性擴大組預(yù)后:39.8%患者治愈或完成治療,38.8%失訪,4.1%死亡,17.3%治療失敗。耐藥性擴大組較藥物敏感性實驗結(jié)果始終未變組預(yù)后差(60%vs;39.8%p0.005)。結(jié)論:結(jié)核病患者在正規(guī)抗結(jié)核治療過程中耐藥性逐漸擴大的現(xiàn)象越來越常見。在非耐多藥結(jié)核病患者中,耐藥性的擴大在抗結(jié)核治療前藥物敏感性實驗結(jié)果表現(xiàn)為多藥耐藥結(jié)核病的患者中較單藥耐藥結(jié)核病患者及全敏感結(jié)核病患者高;過量吸煙史、既往結(jié)核病患者接觸史、影像學(xué)表現(xiàn)為肺部空洞樣病變以及因結(jié)核病多次入院治療史與結(jié)核病患者抗結(jié)核治療過程中耐藥性的擴大密切相關(guān);耐藥性擴大組較藥物敏感性實驗結(jié)果始終未變組預(yù)后差;相關(guān)部門可以采取措施積極發(fā)現(xiàn)結(jié)核病患者中那些存在耐藥性擴大的高危人群,通過加強對該部分患者的管理,進一步改善結(jié)核病患者的遠期預(yù)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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R52

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