本文關(guān)鍵詞：吡嗪酰胺耐藥對肺結(jié)核療效的影響研究　出處：《廣州醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 肺結(jié)核 耐多藥肺結(jié)核 藥物敏感試驗 吡嗪酰胺 耐藥 治療

【摘要】：背景 結(jié)核病是一個古老的疾病，結(jié)核分枝桿菌(人型或牛型)是結(jié)核病的病原體，已與人類共同進化上萬年。結(jié)核病亦是全球最嚴重的公共衛(wèi)生問題之一。在WHO推薦的直接督導(dǎo)下的短程化療（DOTS）方案中，吡嗪酰胺是DOTS方案中重要的抗結(jié)核藥物。結(jié)核病治療失敗的主要原因就是耐藥。耐藥可致結(jié)核病人致死率升高而治愈率降低。 吡嗪酰胺是重要的一線抗結(jié)核藥物，它獨特的作用使加入治療方案中后結(jié)核病9-12個月療程縮短至6個月，同時也是耐多藥肺結(jié)核的治療方案的重要組成部分。WHO在耐多藥結(jié)核病治療原則中建議，吡嗪酰胺應(yīng)貫穿于整個療程。自吡嗪酰胺被廣泛應(yīng)用于短程化療方案中以來,耐吡嗪酰胺的結(jié)核菌有增長的趨勢。美國CDC報告全國吡嗪酰胺耐藥率在1999-2009年以每年2%-3.3%的速率增長。而國內(nèi)缺乏相關(guān)流行病學(xué)數(shù)據(jù)。國外有研究發(fā)現(xiàn)吡嗪酰胺單耐藥的肺結(jié)核患者療效及預(yù)后明顯比全敏患者差。但對于吡嗪酰胺耐藥對肺結(jié)核短期療效的影響尚未見相關(guān)文獻報道。在耐多藥菌株中吡嗪酰胺耐藥率在50%左右。有研究發(fā)現(xiàn)存在吡嗪酰胺耐藥的耐多藥患者預(yù)后可能更差。由于二線藥物較強的毒副作用以及需要更長的療程，使得耐多藥結(jié)核病的治療更加困難。因此,治療早期發(fā)現(xiàn)肺結(jié)核患者吡嗪酰胺耐藥情況，了解吡嗪酰胺耐藥對結(jié)核病治療的影響就顯得愈加重要了。 目的 本課題研究肺結(jié)核病人耐吡嗪酰胺的流行情況，探討吡嗪酰胺耐藥對肺結(jié)核病療效的影響；探討吡嗪酰胺耐藥對耐多藥肺結(jié)核病療效影響。 第一部分肺結(jié)核患者耐吡嗪酰胺流行情況 一、研究對象及方法： 選自2011年-2013年在廣州市胸科醫(yī)院住院診治的菌陽肺結(jié)核病人814例，年齡在12~89歲之間（平均42.7歲）；其中男性517例，，女性297例，（M/F=1.74）；初治肺結(jié)核630例（77.4%），復(fù)治肺結(jié)核184例（22.6%）。 所有病人均在清晨留取深部痰標本，并經(jīng)檢驗人員目視檢查合格，在液體培養(yǎng)基上分離的臨床菌株均采用BACTEC MGIT960法檢測H、R、Z、E、S一線藥物耐藥情況。 二、結(jié)果： 1、肺結(jié)核患者中吡嗪酰胺耐藥率為25.18%，其中單耐吡嗪酰胺為10.2%。 2、肺結(jié)核患者中初治和復(fù)治病人中吡嗪酰胺耐藥率分別為18.41%和48.37%，（χ2=67.827，P=0.000）；涂陽病人和涂陰病人中吡嗪酰胺耐藥率分別為30.53%、20.51%，（χ2=10.79516，P=0.001） 3、耐多藥肺結(jié)核中吡嗪酰胺耐藥率為63.43%。 第二部分吡嗪酰胺耐藥對肺結(jié)核治療的影響 一、研究對象及方法 1、病例選擇：選自2011年-2013年在廣州市胸科醫(yī)院住院治療過的的培陽并涂陽肺結(jié)核病人194例。分為兩組，即吡嗪酰胺敏感組與吡嗪酰胺耐藥組。敏感組共148例，其中男性100例，女性48例，初治患者113例，復(fù)治35例；耐藥組共46例，其中男性24例，女性22例，初治患者36例，復(fù)治10例 2、臨床觀察方法：所有病例均在治療前和治療2月末、6月末清晨留取深部痰標本各4份，采用液體培養(yǎng)法培養(yǎng)1次，陽性菌株分離后做菌種鑒定和藥物敏感試驗，萋-尼抗酸染色法各3次。治療前及治療2月末拍X線（CT）1次。 二、結(jié)果： 1、治療2月末吡嗪酰胺敏感組與耐藥組痰涂片陰轉(zhuǎn)率分別為86.49%、78.26%（χ2=1.816，P=0.178）； 2、治療2月末吡嗪酰胺敏感組與耐藥組病灶改善率分別為78.38%、76.08%（χ2=0.279，P=0.597）； 3、治療2月末吡嗪酰胺敏感組與耐藥組空洞縮小率分別為75.4%、48.65%（χ2=9.623，P=0.002）； 4、治療6月末吡嗪酰胺敏感組與耐藥組痰菌陰轉(zhuǎn)率分別為95.95%、86.96%（χ2=3.461，P=0.063）。 第三部分吡嗪酰胺耐藥對耐多藥結(jié)核病強化期治療的影響 一、研究對象及方法 1、病例選擇：于2011年-2013年在廣州市結(jié)核�？漆t(yī)院住院治療，藥敏結(jié)果提示為耐多藥患者使用耐多藥方案（4～5種藥）后6個月堅持在門診隨診患者。根據(jù)方案組成分為吡嗪酰胺治療組（耐多藥方案中包含吡嗪酰胺），共81例，男52例，女29例，其中根據(jù)吡嗪酰胺藥敏情況又分為吡嗪酰胺敏感組，共31例，男23例，女8例；吡嗪酰胺耐藥組，共50例，男29例，女21例。對照組（耐多藥方案中不包含吡嗪酰胺），共36例，男21例，女15例。 2、臨床觀察方法：所有病例均在治療前和治療6月末清晨留取深部痰標本各4份，采用液體培養(yǎng)法培養(yǎng)1次，陽性菌株分離后做菌種鑒定和藥物敏感試驗，萋-尼染色法各3次。治療前及治療6月末拍X線（CT）1次。 二、結(jié)果： 1、治療6月末有吡嗪酰胺組與無吡嗪酰胺組痰菌陰轉(zhuǎn)率分別為65.43%、44.44%（χ2=4.537，P=0.033）；而其中吡嗪酰胺敏感組與吡嗪酰胺耐藥組分別為67.74%、64.0%（χ2=0.118，P=0.732）； 2、治療6月末有吡嗪酰胺組與無吡嗪酰胺組病灶吸收率分別為74.07%、55.56%，（χ2=3.953，P=0.047）；而其中吡嗪酰胺敏感組與吡嗪酰胺耐藥組分別為83.87%、68.0%（χ2=2.51，P=0.113）； 3、治療6月末有吡嗪酰胺組與無吡嗪酰胺組空洞縮小率分別為42.03%、21.21%（χ2=4.236，P=0.04）；而其中吡嗪酰胺敏感組與吡嗪酰胺耐藥組分別為64.0%、21.21%（χ2=7.767，P=0.005）。 結(jié)論 1、復(fù)治及涂陽肺結(jié)核患者吡嗪酰胺耐藥較高； 2、耐多藥肺結(jié)核患者中吡嗪酰胺耐藥率為63.43%； 3、吡嗪酰胺耐藥患者2月末、6月末痰菌陰轉(zhuǎn)率及病灶吸收率均低于吡嗪酰胺敏感患者，但沒有明顯差異； 4、吡嗪酰胺耐藥肺結(jié)核患者空洞縮小率較低； 5.耐多藥肺結(jié)核治療中加用吡嗪酰胺可提高6月末痰菌陰轉(zhuǎn)率及病灶吸收率； 6、吡嗪酰胺耐藥可降低耐多藥肺結(jié)核患者的空洞縮小率。
[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.

【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R521

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