發(fā)布時間：2018-03-25 15:57

  本文選題：銅綠假單胞菌　切入點：碳青霉烯　出處：《華中科技大學》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)對常用抗菌藥物的年度耐藥狀況，探討導致銅綠假單胞菌耐碳青霉烯的危險因素；研究導致其耐藥的分子生物學機制，為臨床合理用藥，減少耐藥發(fā)生提供依據(jù)。 方法：對本院2001年7月～2004年12月分離的PA進行年耐藥率比較、病區(qū)來源及標本來源分析。采用病例-對照研究方法，運用t檢驗、x~2檢驗、非條件Logistic回歸分析PA對碳青霉烯耐藥的危險因素。稀釋法測定2004年度PA對12種抗菌藥物的MICs值；運用x~2檢驗進行碳青霉烯敏感菌株和耐藥菌株對其他10種抗菌藥物耐藥譜的比較。應用PCR測定28株耐碳青霉烯的PA的IMP和VIM基因，SDS-PAGE測定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PA對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)，對其它大部分抗菌藥物的耐藥率無明顯變化。2001年～2004年PA對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、導管等15種不同的臨床送檢標本，其中痰標本占66.6％。3標本來源：分別來自神經(jīng)外科、呼吸內(nèi)科、ICU、RICU、老年病科等共20余個臨床病區(qū)，其中來自神經(jīng)外科的標本最多，占14.4％。4危險因素分析：分離前15天用過碳青霉烯類抗生素、留置胃管和機械通氣是銅綠假單胞菌對碳青霉烯類抗生素耐藥的獨立危險因素。5碳青霉烯耐藥PA的分子流行病學研究：稀釋法檢測2004年分離的91株PA，發(fā)現(xiàn)28株對碳青霉烯耐藥，對IPM耐藥25株，對MEM耐藥24株，對二者共同耐藥21株。其中檢出多重耐藥株9株，，1株對檢測的12種抗菌藥物全部耐藥。對碳青霉烯耐藥的菌株對其他10種抗假單胞菌藥物的敏感性明顯低于對碳青霉烯敏感的菌株(P＜0.05)。在2004年的28株耐藥菌中，未能擴增出IMP和VIM基因。共有25株耐藥菌有OprD2的表達缺失，其中21株為同時對IPM和MEM耐藥，4株為對IPM耐藥而MEM敏感；而僅對MEM耐藥的3株PA均可檢出與敏感菌表達量相似的OprD2。 結(jié)論：1、深圳市人民醫(yī)院PA的耐藥情況，尤其是對碳青霉烯的耐藥情況十分嚴重。PA主要分離自痰和傷口分泌物，主要來源于神經(jīng)外科、呼吸內(nèi)科、ICU和RICU的患者。2、分離前15天用過碳青霉烯類抗生素、留置胃管和機械通氣是銅綠假單胞菌對碳青霉烯類抗生素耐藥的獨立危險因素。為防止或延緩耐藥PA的產(chǎn)生和傳播，需嚴格控制應用碳青霉烯類抗生素的適應癥、縮短入住ICU的時間及機械通氣的時間、盡量避免留置胃管。3、對碳青霉烯耐藥的28株銅綠假單胞菌中未檢出MMP和VMM基因陽性的菌株，說明產(chǎn)金屬酶不是本院銅綠假單胞菌耐碳青霉烯的主要機制。25株OprD2表達缺失的菌株均為對亞胺培南(IPM)耐藥的菌株，而3株正常表達OprD2的菌株均為對IPM敏感的菌株。這說明OprD2表達缺失是本院銅綠假單胞菌耐IPM的主要機制。25株OprD2表達缺失的菌株中有21株對美羅培南(MEM)耐藥、4株對MEM敏感，而所有正常表達OprD2的菌株均為對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碳青霉烯類抗生素的耐藥機制尚待進一步確認。
[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
緇撹錛

本文編號：1663825