本文選題：銅綠假單胞菌　切入點(diǎn)：碳青霉烯　出處：《華中科技大學(xué)》2006年博士論文

【摘要】： 目的：研究深圳市人民醫(yī)院銅綠假單胞菌(PA)對(duì)常用抗菌藥物的年度耐藥狀況，探討導(dǎo)致銅綠假單胞菌耐碳青霉烯的危險(xiǎn)因素；研究導(dǎo)致其耐藥的分子生物學(xué)機(jī)制，為臨床合理用藥，減少耐藥發(fā)生提供依據(jù)。 方法：對(duì)本院2001年7月～2004年12月分離的PA進(jìn)行年耐藥率比較、病區(qū)來(lái)源及標(biāo)本來(lái)源分析。采用病例-對(duì)照研究方法，運(yùn)用t檢驗(yàn)、x~2檢驗(yàn)、非條件Logistic回歸分析PA對(duì)碳青霉烯耐藥的危險(xiǎn)因素。稀釋法測(cè)定2004年度PA對(duì)12種抗菌藥物的MICs值；運(yùn)用x~2檢驗(yàn)進(jìn)行碳青霉烯敏感菌株和耐藥菌株對(duì)其他10種抗菌藥物耐藥譜的比較。應(yīng)用PCR測(cè)定28株耐碳青霉烯的PA的IMP和VIM基因，SDS-PAGE測(cè)定28株耐藥及2株敏感PA的外膜蛋白OprD2。 結(jié)果：1耐藥情況：2001年7月～2004年12月共分離到銅綠假單胞菌362株，其中2001年54株，2002年82株，2003年135株，2004年91株。362株P(guān)A對(duì)12種臨床常用抗生素的耐藥率在11.6％～57.5％之間，其中以阿米卡星的耐藥率最低。2004年度PA對(duì)頭孢他啶和頭孢吡肟的耐藥率(30.8％和25.3％)較2003年度(15.9％和11.4％)有明顯升高(P＜0.05)，對(duì)哌拉西林和慶大霉素的耐藥率(33.0％和35.2％)較2001年度(52.8％和60.0％)明顯下降(P＜0.05)，對(duì)其它大部分抗菌藥物的耐藥率無(wú)明顯變化。2001年～2004年P(guān)A對(duì)亞胺培南的耐藥率分別為40.7％、33.3％、33.8％和27.5％，而美羅培南的耐藥率分別為36.6％、31.7％、25.6％和26.4％。2標(biāo)本類型：分別為痰液、傷口分泌物、血液、膽汁、腹腔引流液、膿液、尿、胸水、導(dǎo)管等15種不同的臨床送檢標(biāo)本，其中痰標(biāo)本占66.6％。3標(biāo)本來(lái)源：分別來(lái)自神經(jīng)外科、呼吸內(nèi)科、ICU、RICU、老年病科等共20余個(gè)臨床病區(qū)，其中來(lái)自神經(jīng)外科的標(biāo)本最多，占14.4％。4危險(xiǎn)因素分析：分離前15天用過(guò)碳青霉烯類抗生素、留置胃管和機(jī)械通氣是銅綠假單胞菌對(duì)碳青霉烯類抗生素耐藥的獨(dú)立危險(xiǎn)因素。5碳青霉烯耐藥PA的分子流行病學(xué)研究：稀釋法檢測(cè)2004年分離的91株P(guān)A，發(fā)現(xiàn)28株對(duì)碳青霉烯耐藥，對(duì)IPM耐藥25株，對(duì)MEM耐藥24株，對(duì)二者共同耐藥21株。其中檢出多重耐藥株9株，，1株對(duì)檢測(cè)的12種抗菌藥物全部耐藥。對(duì)碳青霉烯耐藥的菌株對(duì)其他10種抗假單胞菌藥物的敏感性明顯低于對(duì)碳青霉烯敏感的菌株(P＜0.05)。在2004年的28株耐藥菌中，未能擴(kuò)增出IMP和VIM基因。共有25株耐藥菌有OprD2的表達(dá)缺失，其中21株為同時(shí)對(duì)IPM和MEM耐藥，4株為對(duì)IPM耐藥而MEM敏感；而僅對(duì)MEM耐藥的3株P(guān)A均可檢出與敏感菌表達(dá)量相似的OprD2。 結(jié)論：1、深圳市人民醫(yī)院PA的耐藥情況，尤其是對(duì)碳青霉烯的耐藥情況十分嚴(yán)重。PA主要分離自痰和傷口分泌物，主要來(lái)源于神經(jīng)外科、呼吸內(nèi)科、ICU和RICU的患者。2、分離前15天用過(guò)碳青霉烯類抗生素、留置胃管和機(jī)械通氣是銅綠假單胞菌對(duì)碳青霉烯類抗生素耐藥的獨(dú)立危險(xiǎn)因素。為防止或延緩耐藥PA的產(chǎn)生和傳播，需嚴(yán)格控制應(yīng)用碳青霉烯類抗生素的適應(yīng)癥、縮短入住ICU的時(shí)間及機(jī)械通氣的時(shí)間、盡量避免留置胃管。3、對(duì)碳青霉烯耐藥的28株銅綠假單胞菌中未檢出MMP和VMM基因陽(yáng)性的菌株，說(shuō)明產(chǎn)金屬酶不是本院銅綠假單胞菌耐碳青霉烯的主要機(jī)制。25株OprD2表達(dá)缺失的菌株均為對(duì)亞胺培南(IPM)耐藥的菌株，而3株正常表達(dá)OprD2的菌株均為對(duì)IPM敏感的菌株。這說(shuō)明OprD2表達(dá)缺失是本院銅綠假單胞菌耐IPM的主要機(jī)制。25株OprD2表達(dá)缺失的菌株中有21株對(duì)美羅培南(MEM)耐藥、4株對(duì)MEM敏感，而所有正常表達(dá)OprD2的菌株均為對(duì)MEM耐藥的菌株，因此OprD2在PA耐MEM中所起的作用尚不十分明了。本院銅綠假單胞菌對(duì)碳青霉烯類抗生素的耐藥機(jī)制尚待進(jìn)一步確認(rèn)。
[Abstract]:Objective: To study the Shenzhen People's Hospital of Pseudomonas aeruginosa (PA) to commonly used antimicrobial drug resistance of the year, to explore the risk factors contributing to carbapenem resistance in Pseudomonas aeruginosa; research in molecular biology mechanism of resistance, for clinical rational use of drugs, reduce drug resistance and provide the basis.
Methods: in our hospital from July 2001 to December 2004 PA years separation resistance rate comparison, analysis in source and source of specimen. In a case-control study, using t test, x~2 test and non conditional Logistic regression analysis PA the carbapenem resistant risk factors. The dilution method for determination of 12 kinds of antibacterial drugs MICs the 2004 annual PA; on the other 10 antimicrobial drug resistance spectrum comparison of carbapenem sensitive strains and resistant strains by x~2 test. IMP PCR was used to determine PA and VIM genes of 28 strains of carbapenem resistant strains, SDS-PAGE were measured in 28 and 2 strains were sensitive to PA outer membrane protein OprD2.
Results: 1 resistance: July 2001 ~ December 2004 were isolated from 362 strains of Pseudomonas aeruginosa, which in 2001 54 strains, 82 strains in 2002, 2003, 2004 and 135 strains of 91.362 strains of PA resistant to 12 commonly used antibiotics in clinic at the rate of 11.6% to 57.5%, with Amikacin of the resistance rate of PA on.2004 year ceftazidime resistance and cefepime rate (30.8% and 25.3%) compared to the year 2003 (15.9% and 11.4%) increased significantly (P < 0.05), resistant to piperacillin and gentamicin rate (33% and 35.2%) compared to the year 2001 (52.8% and 60%) were significantly lower (P < 0.05), to most of the other antimicrobial drug resistance rate has no obvious change in.2001 ~ PA 2004 to imipenem were 40.7%, 33.3%, 33.8% and 27.5%, and meropenem resistance rates were 36.6%, 31.7%, 25.6% and 26.4%.2 respectively were: Sputum, wound secretions, blood, bile, peritoneal fluid, pus, urine, pleural catheter, 15 different clinical specimens, including sputum accounted for 66.6%.3 samples: from the Department of Neurosurgery, Department of respiratory medicine, ICU, RICU, Department of Geriatrics, a total of more than 20 clinical wards, which came from the Department of Neurosurgery the specimens were most, accounted for 14.4%.4 analysis of risk factors: the separation of carbapenem antibiotics for 15 days before the indwelling of nasogastric tube and mechanical ventilation is the molecular epidemiology of Pseudomonas aeruginosa were independent risk factors of carbapenem resistant.5 carbapenem resistant PA detection: 2004 dilution method 91 PA strains found, carbapenem resistant to 28 strains resistant to IPM 25 strains resistant to MEM 24 strains on the two together. The detection of drug resistance of 21 strains of multi drug resistant strains of 9 strains, 1 strains of 12 kinds of antimicrobial agents for detection of all resistant to carbopenems resistance. Drug sensitivity of strains of the other 10 kinds of antipseudomonal drugs were significantly lower than that of the carbapenem resistant strains (P < 0.05). In 28 strains of resistant bacteria in 2004, failed to amplify IMP and VIM gene expression. The lack of a total of 25 strains of resistant bacteria were OprD2, 21 of them were at the same time IPM and MEM resistance, 4 strains were resistant to IPM and MEM sensitive; and only the MEM resistance of the 3 strains of PA were detected with similar amounts of OprD2. and sensitive bacteria expression
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