發(fā)布時(shí)間：2018-07-05 12:44

  本文選題：結(jié)核 + 氟喹諾酮　； 參考：《山東大學(xué)》2015年碩士論文

【摘要】：背景：結(jié)核病(Tuberculosis, TB)仍然是嚴(yán)重危害人類健康的全球性公共衛(wèi)生問題,尤其是耐藥結(jié)核的發(fā)病率不斷上升,給全球結(jié)核控制帶來了巨大挑戰(zhàn)。氟喹諾酮是重要的二線抗結(jié)核藥物,是耐藥結(jié)核病尤其是耐多藥結(jié)核病(Multi-drug resistant tuberculosis, MDR-TB)、復(fù)治以及對(duì)一線藥物不能耐受的初治患者的治療方案的核心。隨著氟喹諾酮類藥物在臨床工作中的廣泛應(yīng)用,結(jié)核分枝桿菌對(duì)氟喹諾酮的耐藥率不斷增加。同時(shí),氟喹諾酮耐藥將導(dǎo)致更多的MDR-TB患者難以治愈,甚至造成泛耐藥結(jié)核(Extensively drug-resistant tuberculosis, XDR-TB)的發(fā)展及蔓延。XDR-TB的高病死率、低治愈率的特點(diǎn)引起了全世界的關(guān)注。本研究通過回顧性臨床分析,了解結(jié)核分枝桿菌對(duì)氟喹諾酮的耐藥情況,探討氟喹諾酮耐藥產(chǎn)生的危險(xiǎn)因素,為指導(dǎo)臨床氟喹諾酮類藥物抗結(jié)核的合理使用及減少耐藥的產(chǎn)生提供依據(jù)。方法：連續(xù)收集山東省胸科醫(yī)院2010年1月1日至2014年10月31日期間所有初治及復(fù)治的肺結(jié)核患者3310例,根據(jù)納入標(biāo)準(zhǔn)及排除標(biāo)準(zhǔn),最后篩選出1954例患者進(jìn)行最后統(tǒng)計(jì)。分析1954例患者的藥物敏感性檢測(cè)結(jié)果(Drug susceptibility testing, DS T)及臨床資料,了解結(jié)核耐藥的情況,同時(shí)探究氟喹諾酮耐藥發(fā)生的獨(dú)立危險(xiǎn)因素。采用SPSS 16.0進(jìn)行數(shù)據(jù)分析,用單變量和多變量logistic回歸分析患者所有的特征因素與氟喹諾酮耐藥的相關(guān)性。用比值比(OR)和可信區(qū)間(CI)評(píng)價(jià)危險(xiǎn)因素與氟喹諾酮耐藥之間的聯(lián)系。以ROC曲線下面積(即C檢驗(yàn))分析檢測(cè)回歸模型的判別能力。結(jié)果：1.1954例患者中總耐藥發(fā)生率為29.7%(581/1954),MDR-TB發(fā)生率為6.4%(122/1954),XDR-TB發(fā)生率為1.4%(27/1954)；抗結(jié)核藥物耐藥發(fā)生率依次為異煙肼(11.4%)、利福平(10.7%)、乙胺丁醇(2.6%)、鏈霉素(14.2%)、氧氟沙星(9.6%)、卷曲霉素(2.6%)、卡那霉素(2.5%)、阿米卡星(2.2%)。2.入選患者中氟喹諾酮耐藥(氧氟沙星耐藥)發(fā)生率為9.6%(188/1954),復(fù)治患者氟喹諾酮耐藥發(fā)生率為19.0%(77/406),明顯高于初治患者7.2%(111/1548),兩者差異有統(tǒng)計(jì)學(xué)意義。氟喹諾酮耐藥患者中以青年患者(18-44歲)居多,占50.5%。有喹諾酮治療史患者耐藥發(fā)生率為24.4%(52/213),明顯高于無喹諾酮治療史患者7.8%(136/1741)。MDR-TB患者耐藥發(fā)生率為22.7%(30/132)也明顯高于非MDR-TB患者8.6%(158/1822)。3.經(jīng)單因素分析,結(jié)果顯示有統(tǒng)計(jì)意義(P0.05)的研究因素有：外來打工人員、復(fù)治、喹諾酮類藥物治療史、空洞、血沉、痰培養(yǎng)合并有其他細(xì)菌、貧血、低白蛋白血癥、支氣管擴(kuò)張、慢性阻塞性肺疾病、耐多藥結(jié)核、患病時(shí)間、住院時(shí)間。將以上因素再進(jìn)行多因素logistic回歸分析,氟喹諾酮耐藥的獨(dú)立危險(xiǎn)因素(OR值及CI)為外來工人(OR 1.44,95% CI：1.05-1.98),復(fù)治(OR 7.66,95% CI：5.13-11.46),喹諾酮藥物治療史(OR 2.73,95% CI：1.97-3.77),痰培養(yǎng)合并有其他細(xì)菌OR(1.01,95% CI：1.00-1.02), 合并低蛋白血癥(OR 2.00,95%CI：1.28-3.13),合并慢性阻塞性肺疾病(OR 3.06,95% CI：2.18-4.30),合并耐多藥結(jié)核(OR 1.82,95%CI：1.14-2.91),患病時(shí)間(OR 1.01,95% CI：1.00-1.01)。ROC分析(C檢驗(yàn))回歸模型有較高的判別氟喹諾酮耐藥的能力,ROC曲線下面積為0.80(95%CI0.77-0.83)。結(jié)論：結(jié)核分枝桿菌對(duì)氟喹諾酮耐藥的總體特點(diǎn)是：青年患者耐藥發(fā)生率多于中老年患者；復(fù)治患者耐藥發(fā)生率多于初治患者；有喹諾酮治療史的患者耐藥發(fā)生率多于無喹諾酮治療史患者；MDR-TB患者耐藥發(fā)生率高于非MDR-TB患者。氟喹諾酮耐藥的獨(dú)立危險(xiǎn)因素分別為：外來工人、復(fù)治、喹諾酮藥物治療史、痰培養(yǎng)合并有其他細(xì)菌、低蛋白血癥、慢性阻塞性肺疾病、耐多藥結(jié)核、結(jié)核患病時(shí)間。
[Abstract]:Background: Tuberculosis (TB) remains a global public health problem that seriously endangers human health, especially the rising incidence of drug-resistant tuberculosis, which poses a great challenge to global tuberculosis control. Fluoroquinolone is an important second-line anti tuberculosis drug, and is a drug resistant TB, especially the Multi-drug resista. NT tuberculosis, MDR-TB), retreatment, and the core of treatment for first - line drugs that are intolerant of first-line drugs. With the widespread use of fluoroquinolones in clinical work, the resistance rate of Mycobacterium tuberculosis to fluoroquinolone is increasing. The development of Extensively drug-resistant tuberculosis (XDR-TB) and the spread of the high mortality and low cure rate of.XDR-TB have attracted worldwide attention. This study is to investigate the resistance of Mycobacterium tuberculosis to fluoroquinolone by retrospective clinical analysis, and to explore the risk factors of fluoroquinolone resistance. To guide the rational use of anti tuberculosis of clinical fluoroquinolone drugs and to reduce the production of drug resistance. Methods: 3310 cases of tuberculosis patients in Shandong thoracic hospital from January 1, 2010 to October 31, 2014 were collected, and 1954 cases were selected according to the standards and exclusion criteria. Post statistics. Analysis of the drug sensitivity test results of 1954 patients (Drug susceptibility testing, DS T) and clinical data to understand the drug resistance of tuberculosis and explore the independent risk factors of fluoroquinolone resistance. The data were analyzed with SPSS 16, and all the patients were analyzed by single variable and multivariable logistic regression. Correlation between the resistance to fluoroquinolone. The relationship between the risk factors and fluoroquinolone resistance was evaluated with the ratio Ratio (OR) and the confidence interval (CI). The discriminant ability of the regression model was detected by the area under the ROC curve (i.e., C test). Results: the incidence of total resistance was 29.7% (581/1954) in 1.1954 cases, and the incidence of MDR-TB was 6.4% (122/1954), XD The incidence of R-TB was 1.4% (27/1954), and the incidence of anti tuberculosis drug resistance was isoniazid (11.4%), rifampicin (10.7%), ethambutol (2.6%), streptomycin (14.2%), ofloxacin (9.6%), Aspergillus (2.6%), kanamycin (2.5%), and the incidence of fluoroquinolone resistance (ofloxacin resistance) in Amikacin (2.2%).2. patients was 9.6% (188/1954), The rate of fluoroquinolone resistance in the retreated patients was 19% (77/406), which was significantly higher than that of the first treated patients (111/1548). The difference was statistically significant. Among the patients with fluoroquinolone, the majority of the patients were young (18-44 years old), and the rate of drug resistance in the history of quinolone treatment was 24.4% (52/213), which was significantly higher than that of the patients without the history of quinolone treatment (13 (13) (13). 6/1741) the incidence of drug resistance in.MDR-TB patients was 22.7% (30/132) and was significantly higher than that of 8.6% (158/1822).3. in non MDR-TB patients. The results showed that there were statistical significance (P0.05): migrant workers, retreatment, history of quinolone treatment, cavity, erythrocyte sedimentation, and sputum culture with other bacteria, anemia, and hypoalbuminemia, Bronchiectasis, chronic obstructive pulmonary disease, multi drug resistant tuberculosis, time of disease, time of hospitalization. The above factors were analyzed by multiple factor Logistic regression analysis, independent risk factors of fluoroquinolone resistance (OR value and CI) were foreign workers (OR 1.44,95% CI:1.05-1.98), retreatment (OR 7.66,95% CI:5.13-11.46), and the history of quinolone medication (OR 2.7) 3,95% CI:1.97-3.77), sputum culture combined with other bacteria OR (1.01,95% CI:1.00-1.02), combined with low proteinemia (OR 2.00,95%CI:1.28-3.13), combined with chronic obstructive pulmonary disease (OR 3.06,95% CI:2.18-4.30), combined with multidrug resistant tuberculosis (OR 1.82,95%CI:1.14-2.91). The regression model has a high ability to discriminate fluoroquinolone resistance, and the area under the ROC curve is 0.80 (95%CI0.77-0.83). Conclusion: the overall characteristics of the resistance of Mycobacterium tuberculosis to fluoroquinolone are that the incidence of drug resistance in young patients is more than that of the middle aged and old patients; the rate of drug resistance in the retreated patients is more than that of the primary treatment patients; the patients with the history of quinolone treatment have a history of quinolone treatment. The incidence of drug resistance was more than those without the history of quinolone treatment; the incidence of drug resistance in MDR-TB patients was higher than that in non MDR-TB patients. The independent risk factors of fluoroquinolone resistance were foreign workers, retreatment, the history of quinolone medication, sputum culture combined with other bacteria, hypoproteinemia, chronic obstructive pulmonary disease, multi drug resistant tuberculosis, and tuberculosis. Room.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R446.5

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