吡嗪酰胺耐药对肺结核疗效的影响研究

发布时间：2018-01-13 17:31

本文关键词：吡嗪酰胺耐药对肺结核疗效的影响研究　出处：《广州医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景结核病是一个古老的疾病，结核分枝杆菌(人型或牛型)是结核病的病原体，已与人类共同进化上万年。结核病亦是全球最严重的公共卫生问题之一。在WHO推荐的直接督导下的短程化疗（DOTS）方案中，吡嗪酰胺是DOTS方案中重要的抗结核药物。结核病治疗失败的主要原因就是耐药。耐药可致结核病人致死率升高而治愈率降低。吡嗪酰胺是重要的一线抗结核药物，它独特的作用使加入治疗方案中后结核病9-12个月疗程缩短至6个月，同时也是耐多药肺结核的治疗方案的重要组成部分。WHO在耐多药结核病治疗原则中建议，吡嗪酰胺应贯穿于整个疗程。自吡嗪酰胺被广泛应用于短程化疗方案中以来,耐吡嗪酰胺的结核菌有增长的趋势。美国CDC报告全国吡嗪酰胺耐药率在1999-2009年以每年2%-3.3%的速率增长。而国内缺乏相关流行病学数据。国外有研究发现吡嗪酰胺单耐药的肺结核患者疗效及预后明显比全敏患者差。但对于吡嗪酰胺耐药对肺结核短期疗效的影响尚未见相关文献报道。在耐多药菌株中吡嗪酰胺耐药率在50%左右。有研究发现存在吡嗪酰胺耐药的耐多药患者预后可能更差。由于二线药物较强的毒副作用以及需要更长的疗程，使得耐多药结核病的治疗更加困难。因此,治疗早期发现肺结核患者吡嗪酰胺耐药情况，了解吡嗪酰胺耐药对结核病治疗的影响就显得愈加重要了。目的本课题研究肺结核病人耐吡嗪酰胺的流行情况，探讨吡嗪酰胺耐药对肺结核病疗效的影响；探讨吡嗪酰胺耐药对耐多药肺结核病疗效影响。第一部分肺结核患者耐吡嗪酰胺流行情况一、研究对象及方法：选自2011年-2013年在广州市胸科医院住院诊治的菌阳肺结核病人814例，年龄在12~89岁之间（平均42.7岁）；其中男性517例，，女性297例，（M/F=1.74）；初治肺结核630例（77.4%），复治肺结核184例（22.6%）。所有病人均在清晨留取深部痰标本，并经检验人员目视检查合格，在液体培养基上分离的临床菌株均采用BACTEC MGIT960法检测H、R、Z、E、S一线药物耐药情况。二、结果： 1、肺结核患者中吡嗪酰胺耐药率为25.18%，其中单耐吡嗪酰胺为10.2%。 2、肺结核患者中初治和复治病人中吡嗪酰胺耐药率分别为18.41%和48.37%，（χ2=67.827，P=0.000）；涂阳病人和涂阴病人中吡嗪酰胺耐药率分别为30.53%、20.51%，（χ2=10.79516，P=0.001） 3、耐多药肺结核中吡嗪酰胺耐药率为63.43%。第二部分吡嗪酰胺耐药对肺结核治疗的影响一、研究对象及方法 1、病例选择：选自2011年-2013年在广州市胸科医院住院治疗过的的培阳并涂阳肺结核病人194例。分为两组，即吡嗪酰胺敏感组与吡嗪酰胺耐药组。敏感组共148例，其中男性100例，女性48例，初治患者113例，复治35例；耐药组共46例，其中男性24例，女性22例，初治患者36例，复治10例 2、临床观察方法：所有病例均在治疗前和治疗2月末、6月末清晨留取深部痰标本各4份，采用液体培养法培养1次，阳性菌株分离后做菌种鉴定和药物敏感试验，萋-尼抗酸染色法各3次。治疗前及治疗2月末拍X线（CT）1次。二、结果： 1、治疗2月末吡嗪酰胺敏感组与耐药组痰涂片阴转率分别为86.49%、78.26%（χ2=1.816，P=0.178）； 2、治疗2月末吡嗪酰胺敏感组与耐药组病灶改善率分别为78.38%、76.08%（χ2=0.279，P=0.597）； 3、治疗2月末吡嗪酰胺敏感组与耐药组空洞缩小率分别为75.4%、48.65%（χ2=9.623，P=0.002）； 4、治疗6月末吡嗪酰胺敏感组与耐药组痰菌阴转率分别为95.95%、86.96%（χ2=3.461，P=0.063）。第三部分吡嗪酰胺耐药对耐多药结核病强化期治疗的影响一、研究对象及方法 1、病例选择：于2011年-2013年在广州市结核专科医院住院治疗，药敏结果提示为耐多药患者使用耐多药方案（4～5种药）后6个月坚持在门诊随诊患者。根据方案组成分为吡嗪酰胺治疗组（耐多药方案中包含吡嗪酰胺），共81例，男52例，女29例，其中根据吡嗪酰胺药敏情况又分为吡嗪酰胺敏感组，共31例，男23例，女8例；吡嗪酰胺耐药组，共50例，男29例，女21例。对照组（耐多药方案中不包含吡嗪酰胺），共36例，男21例，女15例。 2、临床观察方法：所有病例均在治疗前和治疗6月末清晨留取深部痰标本各4份，采用液体培养法培养1次，阳性菌株分离后做菌种鉴定和药物敏感试验，萋-尼染色法各3次。治疗前及治疗6月末拍X线（CT）1次。二、结果： 1、治疗6月末有吡嗪酰胺组与无吡嗪酰胺组痰菌阴转率分别为65.43%、44.44%（χ2=4.537，P=0.033）；而其中吡嗪酰胺敏感组与吡嗪酰胺耐药组分别为67.74%、64.0%（χ2=0.118，P=0.732）； 2、治疗6月末有吡嗪酰胺组与无吡嗪酰胺组病灶吸收率分别为74.07%、55.56%，（χ2=3.953，P=0.047）；而其中吡嗪酰胺敏感组与吡嗪酰胺耐药组分别为83.87%、68.0%（χ2=2.51，P=0.113）； 3、治疗6月末有吡嗪酰胺组与无吡嗪酰胺组空洞缩小率分别为42.03%、21.21%（χ2=4.236，P=0.04）；而其中吡嗪酰胺敏感组与吡嗪酰胺耐药组分别为64.0%、21.21%（χ2=7.767，P=0.005）。结论 1、复治及涂阳肺结核患者吡嗪酰胺耐药较高； 2、耐多药肺结核患者中吡嗪酰胺耐药率为63.43%； 3、吡嗪酰胺耐药患者2月末、6月末痰菌阴转率及病灶吸收率均低于吡嗪酰胺敏感患者，但没有明显差异； 4、吡嗪酰胺耐药肺结核患者空洞缩小率较低； 5.耐多药肺结核治疗中加用吡嗪酰胺可提高6月末痰菌阴转率及病灶吸收率； 6、吡嗪酰胺耐药可降低耐多药肺结核患者的空洞缩小率。
[Abstract]:background
Tuberculosis is an ancient disease, Mycobacterium tuberculosis (human or bovine) is the causative agent of tuberculosis, has co evolved with humans million years. Tuberculosis is one of the most serious public health problems in the world. Under the direct supervision of the WHO recommended short-term chemotherapy (DOTS) scheme, pyrazinamide is anti tuberculosis the most important drug in the DOTS scheme. The main reason for treatment failure is resistant. Drug resistance tuberculosis patients can increase the mortality and the cure rate is reduced.
Pyrazinamide is an important first-line anti tuberculosis drugs, its unique role to join in the treatment of tuberculosis after 9-12 months of treatment shortened to 6 months, but also an important part of treatment of multi drug resistant pulmonary tuberculosis.WHO in multi drug resistant tuberculosis treatment principle suggested that pyrazine amide should be throughout the entire course of treatment. Since pyrazinamide is widely used in short term chemotherapy, resistant to pyrazinamide TB increase. The CDC report of the national pyrazinamide resistance rate grew at an annual rate of 2%-3.3% in 1999-2009. And the lack of relevant domestic epidemiological data. Foreign studies have found that the curative effect and prognosis of patients with pulmonary tuberculosis were significantly higher than the single pyrazinamide resistance sensitive patients poor. But the influence of pyrazinamide resistant pulmonary tuberculosis short-term effect has not been reported in the literature. Multidrug resistant strains of pyrazinamide resistant rate At about 50%. The study found that the presence of pyrazinamide resistant patients with multi drug resistant prognosis may be worse. Due to strong side effects of second-line drugs and treatment need longer, making the treatment of multi drug resistant tuberculosis more difficult. Therefore, the treatment of pulmonary tuberculosis patients in the early detection of amide resistance, pyrazinamide resistant effect on understanding the treatment of tuberculosis becomes increasingly important.
objective
The epidemic situation of tuberculosis patients in this study to investigate the effect of pyrazinamide resistant pyrazinamide, resistant to the curative effect of pulmonary tuberculosis; to investigate the effect of pyrazinamide resistant to multiple drug resistant pulmonary tuberculosis curative effect.
The first part of the epidemic situation of pyrazinamide resistant pulmonary tuberculosis patients
First, research objects and methods:
A total of 814 cases of sputum positive pulmonary tuberculosis in Guangzhou chest hospital from 2011 to 2011 were selected, aged from -2013 years old (average 42.7 years), including 517 males and 297 females (M/F=1.74). 630 cases (77.4%) were newly diagnosed with pulmonary tuberculosis, 184 cases (22.6%) were retreated tuberculosis.
All patients received deep sputum specimens in the early morning, and were inspected by the inspectors. The clinical isolates isolated from liquid culture were detected by BACTEC MGIT960 for H, R, Z, E and S.
Two, results:
1 patients with pulmonary tuberculosis in pyrazinamide resistant rate was 25.18%, which is 10.2%. single pyrazinamide resistance
2, initial treatment and retreatment of pulmonary tuberculosis patients with pyrazinamide resistance rates were 18.41% and 48.37% (2=67.827, P=0.000); smear positive and smear negative patients in pyrazinamide resistance rates were 30.53%, 20.51%, (2=10.79516, P=0.001)
3, multi drug resistant tuberculosis in pyrazinamide resistant rate was 63.43%.
The second part of pyrazinamide resistant tuberculosis
First, the object and method of research
1, case selection: from 2011 -2013 in Guangzhou chest hospital treated 194 cases of culture positive and smear positive tuberculosis patients. Divided into two groups, namely pyrazinamide sensitive group and pyrazinamide resistant group. Sensitive group were 148 cases, including 100 cases of male, female 48 cases, 113 cases of newly diagnosed patients, 35 cases of retreatment; resistant group were 46 cases, including 24 cases of male, female 22 cases, 36 cases of newly diagnosed patients, 10 cases of retreatment
2, clinical observation methods: all patients before treatment and at the end of 2, 6 at the end of the morning sputum was collected 4 samples of the deep, liquid culture 1, positive strains were isolated after identification and drug sensitivity test, Ziehl Neelsen acid fast stain 3 times before treatment and treatment. At the end of 2 medical X-ray (CT) 1 times.
Two, results:
1, 2 at the end of treatment of pyrazinamide sensitive group and resistant group sputum smear negative conversion rate were 86.49%, 78.26% (2=1.816, P=0.178);
2, 2 at the end of treatment group and drug resistant group pyrazinamide sensitive lesion improvement rate were 78.38%, 76.08% (2=0.279, P=0.597);
3, 2 at the end of treatment with pyrazinamide sensitive group resistance group, cavity closing rate is respectively 75.4%, 48.65% (2=9.623, P=0.002);
4, 6 at the end of treatment of pyrazinamide sensitive group and resistant group the sputum negative conversion rate were 95.95%, 86.96% (2=3.461, P=0.063).
The third part to strengthen the effect of pyrazinamide resistant treatment of multi drug resistant tuberculosis
First, the object and method of research
1 cases: in 2011 -2013 in Guangzhou tuberculosis hospital inpatient treatment, drug sensitivity results for the multi drug resistance in patients with multi drug resistant scheme (4 ~ 5 drugs) 6 months after persist in outpatient follow-up patients. According to the scheme of the composition is divided into treatment group (pyrazinamide resistant prescription case contains a total of 81 cases), pyrazinamide, male 52 cases, female 29 cases, according to the drug sensitivity of pyrazinamide was divided into pyrazinamide sensitive group, a total of 31 cases, male 23 cases, female 8 cases; pyrazinamide resistant group, a total of 50 cases, male 29 cases, female 21 cases. The control group (multi drug resistant scheme not included), pyrazinamide were 36 cases, 21 cases were male, 15 were female.
2, clinical observation methods: all patients before treatment and at the end of 6 morning sputum was collected 4 samples of the deep, liquid culture 1, positive strains were isolated after identification and drug sensitivity test, Ziehl Neelsen staining method 3 times each. Before treatment and at the end of 6 radiographs (CT) 1 times.
Two, results:
1, 6 at the end of treatment with pyrazinamide group and non pyrazinamide sputum were 65.43%, 44.44% (2=4.537, P=0.033); and the pyrazinamide sensitive group and pyrazinamide resistant group were 67.74% and 64% (2=0.118, P=0.732);
2, 6 at the end of treatment with pyrazinamide group and non group pyrazinamide lesions absorption rate were 74.07%, 55.56%, (2=3.953, P=0.047); and the pyrazinamide sensitive group and pyrazinamide resistant group were 83.87% and 68% (2=2.51, P=0.113);
3, 6 at the end of treatment with pyrazinamide group and non group pyrazinamide syringomyelia were 42.03%, 21.21% (2=4.236, P=0.04); and the pyrazinamide sensitive group and pyrazinamide resistant group were 64% and 21.21% (2=7.767, P=0.005).
conclusion
1, retreatment smear positive pulmonary tuberculosis patients and pyrazinamide resistance is higher;
2 patients with multi drug resistant pulmonary tuberculosis in pyrazinamide resistant rate was 63.43%;
3, pyrazinamide resistant patients at the end of 2, 6 at the end of the sputum negative conversion rate and focus absorption rate was lower than that of pyrazinamide sensitive patients, but no significant difference;
4, pyrazinamide resistant patients with pulmonary tuberculosis cavity closing rate is low;
5. multi drug resistant pulmonary tuberculosis treatment with pyrazinamide can improve 6 sputum negative conversion rate and focus absorption rate;
6, pyrazinamide resistant can reduce multi drug resistant pulmonary tuberculosis cavity closing rate.

【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R521

【参考文献】