结核分枝杆菌对氟喹诺酮耐药现状及危险因素的回顾性临床分析

发布时间：2018-07-05 12:44

本文选题：结核 + 氟喹诺酮　；参考：《山东大学》2015年硕士论文

【摘要】：背景：结核病(Tuberculosis, TB)仍然是严重危害人类健康的全球性公共卫生问题,尤其是耐药结核的发病率不断上升,给全球结核控制带来了巨大挑战。氟喹诺酮是重要的二线抗结核药物,是耐药结核病尤其是耐多药结核病(Multi-drug resistant tuberculosis, MDR-TB)、复治以及对一线药物不能耐受的初治患者的治疗方案的核心。随着氟喹诺酮类药物在临床工作中的广泛应用,结核分枝杆菌对氟喹诺酮的耐药率不断增加。同时,氟喹诺酮耐药将导致更多的MDR-TB患者难以治愈,甚至造成泛耐药结核(Extensively drug-resistant tuberculosis, XDR-TB)的发展及蔓延。XDR-TB的高病死率、低治愈率的特点引起了全世界的关注。本研究通过回顾性临床分析,了解结核分枝杆菌对氟喹诺酮的耐药情况,探讨氟喹诺酮耐药产生的危险因素,为指导临床氟喹诺酮类药物抗结核的合理使用及减少耐药的产生提供依据。方法：连续收集山东省胸科医院2010年1月1日至2014年10月31日期间所有初治及复治的肺结核患者3310例,根据纳入标准及排除标准,最后筛选出1954例患者进行最后统计。分析1954例患者的药物敏感性检测结果(Drug susceptibility testing, DS T)及临床资料,了解结核耐药的情况,同时探究氟喹诺酮耐药发生的独立危险因素。采用SPSS 16.0进行数据分析,用单变量和多变量logistic回归分析患者所有的特征因素与氟喹诺酮耐药的相关性。用比值比(OR)和可信区间(CI)评价危险因素与氟喹诺酮耐药之间的联系。以ROC曲线下面积(即C检验)分析检测回归模型的判别能力。结果：1.1954例患者中总耐药发生率为29.7%(581/1954),MDR-TB发生率为6.4%(122/1954),XDR-TB发生率为1.4%(27/1954)；抗结核药物耐药发生率依次为异烟肼(11.4%)、利福平(10.7%)、乙胺丁醇(2.6%)、链霉素(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.入选患者中氟喹诺酮耐药(氧氟沙星耐药)发生率为9.6%(188/1954),复治患者氟喹诺酮耐药发生率为19.0%(77/406),明显高于初治患者7.2%(111/1548),两者差异有统计学意义。氟喹诺酮耐药患者中以青年患者(18-44岁)居多,占50.5%。有喹诺酮治疗史患者耐药发生率为24.4%(52/213),明显高于无喹诺酮治疗史患者7.8%(136/1741)。MDR-TB患者耐药发生率为22.7%(30/132)也明显高于非MDR-TB患者8.6%(158/1822)。3.经单因素分析,结果显示有统计意义(P0.05)的研究因素有：外来打工人员、复治、喹诺酮类药物治疗史、空洞、血沉、痰培养合并有其他细菌、贫血、低白蛋白血症、支气管扩张、慢性阻塞性肺疾病、耐多药结核、患病时间、住院时间。将以上因素再进行多因素logistic回归分析,氟喹诺酮耐药的独立危险因素(OR值及CI)为外来工人(OR 1.44,95% CI：1.05-1.98),复治(OR 7.66,95% CI：5.13-11.46),喹诺酮药物治疗史(OR 2.73,95% CI：1.97-3.77),痰培养合并有其他细菌OR(1.01,95% CI：1.00-1.02), 合并低蛋白血症(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),合并耐多药结核(OR 1.82,95%CI：1.14-2.91),患病时间(OR 1.01,95% CI：1.00-1.01)。ROC分析(C检验)回归模型有较高的判别氟喹诺酮耐药的能力,ROC曲线下面积为0.80(95%CI0.77-0.83)。结论：结核分枝杆菌对氟喹诺酮耐药的总体特点是：青年患者耐药发生率多于中老年患者；复治患者耐药发生率多于初治患者；有喹诺酮治疗史的患者耐药发生率多于无喹诺酮治疗史患者；MDR-TB患者耐药发生率高于非MDR-TB患者。氟喹诺酮耐药的独立危险因素分别为：外来工人、复治、喹诺酮药物治疗史、痰培养合并有其他细菌、低蛋白血症、慢性阻塞性肺疾病、耐多药结核、结核患病时间。
[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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R446.5

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