耐碳青霉烯铜绿假单胞菌的分子流行病学研究
发布时间：2018-03-25 15:57
本文选题：铜绿假单胞菌 切入点：碳青霉烯 出处：《华中科技大学》2006年博士论文
【摘要】： 目的：研究深圳市人民医院铜绿假单胞菌(PA)对常用抗菌药物的年度耐药状况，探讨导致铜绿假单胞菌耐碳青霉烯的危险因素；研究导致其耐药的分子生物学机制，为临床合理用药，减少耐药发生提供依据。 方法：对本院2001年7月～2004年12月分离的PA进行年耐药率比较、病区来源及标本来源分析。采用病例-对照研究方法，运用t检验、x~2检验、非条件Logistic回归分析PA对碳青霉烯耐药的危险因素。稀释法测定2004年度PA对12种抗菌药物的MICs值；运用x~2检验进行碳青霉烯敏感菌株和耐药菌株对其他10种抗菌药物耐药谱的比较。应用PCR测定28株耐碳青霉烯的PA的IMP和VIM基因，SDS-PAGE测定28株耐药及2株敏感PA的外膜蛋白OprD2。 结果：1耐药情况：2001年7月～2004年12月共分离到铜绿假单胞菌362株，其中2001年54株，2002年82株，2003年135株，2004年91株。362株PA对12种临床常用抗生素的耐药率在11.6％～57.5％之间，其中以阿米卡星的耐药率最低。2004年度PA对头孢他啶和头孢吡肟的耐药率(30.8％和25.3％)较2003年度(15.9％和11.4％)有明显升高(P＜0.05)，对哌拉西林和庆大霉素的耐药率(33.0％和35.2％)较2001年度(52.8％和60.0％)明显下降(P＜0.05)，对其它大部分抗菌药物的耐药率无明显变化。2001年～2004年PA对亚胺培南的耐药率分别为40.7％、33.3％、33.8％和27.5％，而美罗培南的耐药率分别为36.6％、31.7％、25.6％和26.4％。2标本类型：分别为痰液、伤口分泌物、血液、胆汁、腹腔引流液、脓液、尿、胸水、导管等15种不同的临床送检标本，其中痰标本占66.6％。3标本来源：分别来自神经外科、呼吸内科、ICU、RICU、老年病科等共20余个临床病区，其中来自神经外科的标本最多，占14.4％。4危险因素分析：分离前15天用过碳青霉烯类抗生素、留置胃管和机械通气是铜绿假单胞菌对碳青霉烯类抗生素耐药的独立危险因素。5碳青霉烯耐药PA的分子流行病学研究：稀释法检测2004年分离的91株PA，发现28株对碳青霉烯耐药，对IPM耐药25株，对MEM耐药24株，对二者共同耐药21株。其中检出多重耐药株9株，，1株对检测的12种抗菌药物全部耐药。对碳青霉烯耐药的菌株对其他10种抗假单胞菌药物的敏感性明显低于对碳青霉烯敏感的菌株(P＜0.05)。在2004年的28株耐药菌中，未能扩增出IMP和VIM基因。共有25株耐药菌有OprD2的表达缺失，其中21株为同时对IPM和MEM耐药，4株为对IPM耐药而MEM敏感；而仅对MEM耐药的3株PA均可检出与敏感菌表达量相似的OprD2。 结论：1、深圳市人民医院PA的耐药情况，尤其是对碳青霉烯的耐药情况十分严重。PA主要分离自痰和伤口分泌物，主要来源于神经外科、呼吸内科、ICU和RICU的患者。2、分离前15天用过碳青霉烯类抗生素、留置胃管和机械通气是铜绿假单胞菌对碳青霉烯类抗生素耐药的独立危险因素。为防止或延缓耐药PA的产生和传播，需严格控制应用碳青霉烯类抗生素的适应症、缩短入住ICU的时间及机械通气的时间、尽量避免留置胃管。3、对碳青霉烯耐药的28株铜绿假单胞菌中未检出MMP和VMM基因阳性的菌株，说明产金属酶不是本院铜绿假单胞菌耐碳青霉烯的主要机制。25株OprD2表达缺失的菌株均为对亚胺培南(IPM)耐药的菌株，而3株正常表达OprD2的菌株均为对IPM敏感的菌株。这说明OprD2表达缺失是本院铜绿假单胞菌耐IPM的主要机制。25株OprD2表达缺失的菌株中有21株对美罗培南(MEM)耐药、4株对MEM敏感，而所有正常表达OprD2的菌株均为对MEM耐药的菌株，因此OprD2在PA耐MEM中所起的作用尚不十分明了。本院铜绿假单胞菌对碳青霉烯类抗生素的耐药机制尚待进一步确认。
[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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