呼吸机相关性肺炎的病原学特点

呼吸机相关性肺炎的病原学特点及其对临床预后的影响1

1

李秀华2（1.南京医科大学附属南京第一医院急诊科，江苏南京210006；2.上海市浦东新区周浦医院重症医学科，上海201318）[摘要]目的：用回顾性研究的方法调查我院重症监护室呼吸机相关性肺炎（ventilator-associated我们回20136201412(VAP组)和非呼吸机相关性肺炎组(NON-VAP组)，并对VAPVAPVAPVAP9679患者中72例患者（84.71%）为多细菌感染；早发型VAP3638VAP4958VAP7VAP24VAP和晚发型VAP8.49±4.36vs.28.11±25.51vs.50.00%58.33%VAP和NON-VAP16.82±38.8324.16±40.42vs.11.79±11.63（P=0.007），54.12%vs.ICU中早发型VAPVAPVAPVAPVAP延长ICU患者的机械通气时间及ICU[关键词]：呼吸机相关性肺炎；重症监护室；病原体；多重耐药Themicrobialaetiologyofventilator-associatedpneumoniaanditseffectonclinicalprognosisZHANGSu-hua1,ZHU-Jin1，LI-Xiu-hua2（1.EmergencyDepartment,NanjingFirstHospitalAffiliatedto210006，China 2.）[Abstract]Objective:WeretrospectivelyinvestigatedmicrobialaetiologyandtheimpactonclinicaloutcomesofVAPinICUsinourhospital.Methods:PatientswhowereadmittedtoICUofourhospitalandweremechanicallyventilatedfor＞48hfromJune2013andtoDecmber2014wereretrospectivelyinvestigated.Allthesepatientsweredividedintotwogroups,ventilator-associatedpneumoniagroup(VAPgroup)andnon-ventilator-associatedpneumoniagroup(NON-VAPgroup).Furthermore,VAPgroupwasdividedintotwogroups,early-onsetVAPandlate-onsetVAP.Respiratorysecretionsofallpatientswerecultured.Thenclinicaloutcomesofpatientswerereviewedineachgroup.Results:96bacterialisolateswereculturedfrom85patientswithVAP.Therewere79gram-negativebacterias(82.29%),mostofwhichwerePseudomonasaeruginosa,AcinetobactersppandKlebsiellapneumoniae.72patients(84.71%)withVAPhadmonomicrobialinfectionand13patients(15.29%)hadpolymicrobialinfection.38isolateswereculturedfrom36patientswithearly-onsetVAP,mainlyincludingKlebsiellapneumoniae,PseudomonasaeruginosaandStaphylococcusaureus.58isolateswereculturedfrom49patientswithlate-onsetVAP,whichmainlywereAcinetobacterbaumannii,PseudomonasaeruginosaandKlebsiellapneumoniae.7multi-drugresistantpathogenswereobtainedfrompatientswithearly-onsetVAP,while24isolateswereobtainedfromlate-onsetVAP.Andthemulti-drugresistantpathogensinthetwogroupswerestatisticallysignificant(P=0.021).Daysformechanicalventilationofearly-onsetVAPandlate-onsetVAPwere8.49 ±4.36versus26.0614.90(P=0.001)respectively.Thetotaldaysofhospitalizationwere28.11±25.51versus42.88±31.41(P=0.020).Andthe30-daymortalitywas50.00%versus35.42%(P=0.180),the60-daymortalitywere58.33%versus45.83%(P=0.257).DaysformechanicalventilationinVAPgroupandNON-VAPgroupwere16.82±38.83versus6.66±5.28(P=0.018).AndthetotaldaysofICUstaywere24.16±40.42versus11.79±11.63(P=0.007)respectively.Themortalityduringhospitalizationwas54.12%versus39.67%(P=0.023)betweenthetwogroups.Pseudomonasaeruginosa,AcinetobactersppandKlebsiellapneumoniaeweremostcommoninVAPpathogensintheICUsofourhospital.Pathogensinearly-onsetVAPmainlywereKlebsiellapneumoniae,PseudomonasaeruginosaandStaphylococcusaureus,whilethepathogensinlate-onsetVAPmainlywereAcinetobacterbaumannii,PseudomonasaeruginosaandKlebsiellapneumoniae.Muti-drugresistantpathogensaremorecommoninlate-onsetVAP.VAPprolongsventilatordaysandICUstay,increasesthemortalityofcriticalpatientsduringhospitalizationatthesametime.Durationofmechanicalventilationandtotalhospitalizationoflate-onsetVAPwerelongerthanthatofearly-onsetVAP,whilethemortalityofthetwogroupwerenotstatisticallydifferent.Keywords:ventilator-associatedpneumoniintensivecareunimicrobialresistantVentilator-associated48h48h内出现的VAP[1]IC者病死率[3]。

增加患按发病时间不同，将VAP分为早发型及晚发型呼吸机相关性肺炎，早发型VAP是指机48h5dVAP5dVAP（金黄色葡萄球菌、肺炎链球菌及流感嗜血杆菌）和口腔中厌氧菌感染所引起的，而晚发VAP的病原体中多重细菌感染比例增高，并伴有更高的发病率及病死率[4，5]；但是，也有观点认为前MDR在早发型和晚发型VAP流行性无显著差异[6]，因此对早发型VAP和晚发型VAP致病菌分布特点以及早发型及晚发型VAP患者预后情况仍需要进一步研究。20136201412月期间我院ICU48VAPVAPNON-VAPVAPVAP对象和方法对象：对我院ICU20130620141232748VAP327名患者分为VAP组及NON-VAPVAP85例，男3123-94NON-VAP242153897-97VAP85VAP，VAP2013[7]推荐的方法执行。方法机械通气患者接受集束化处理措施接受机械通气的患者都要接受相同处理（1）床头高度30-4（）每日均给予常规全胸片检查Ramsay3-4分，并按Kress每天用生理盐水清洗口腔三至四次来保持口腔清洁（5）根据病情使用H2受体阻滞剂或者质子泵抑制剂来预防应激性溃疡（）每位医务工作者在接触患者前后均进行卫生手消毒；（7）加强对呼吸机管道管理，及时清除呼吸机管路的冷凝水，并定期监测套囊压力，保持在20-25cmHO（）2液标本进行培养及药敏试验。机械通气患者的治疗327名机械通气患者除了进行气管插管或气切套管接呼吸机辅助通气外，还给予针对原发病的治疗，并辅以抑酸、化痰、抗感染、保护各脏器功能、预防并发症、维持循环及内环境稳定等综合治疗。呼吸道分泌物的采集和培养对VAP疑似病例用气管导管内吸引呼吸道分泌物方法获取下呼吸道标本2-5ml观察指标临床数据以ExcelICUAPACHEII[9]、VAPICU60统计学处理（X±sSPSS19.0tWilcoxon则说明存在的差异具有统计学意义。结果VAP本研究中327例患者有85例患者被诊断为VAP，其患病率为25.99%，VAP组和NON-VAP组患者在性别、年龄、APACHEII评分及原发疾病上差异均无统计差异（表1）。85VAP85VAP9679最常见的为：铜绿假单胞菌、鲍氏不动杆菌及肺炎克雷伯杆菌；革兰氏阳性菌有10株，占10.42%，以金黄色葡萄球菌为主，其中MRSA8株，占80%；真菌有7株，占7.29%，以白72例患者（84.71%）例患者（15.29%）为多细菌感染（表2）.早发型VAPVAP早发型VAP3638VAP49例，培养出58绿假单胞菌及肺炎克雷伯菌（3）.早发型与晚发型VAPVAP718.42VAP24株，检出率为41.38%，多重耐药菌更常见于晚发型VAP（表4）。早发型与晚发型VAPVAP机械通气天数要短于晚发型VAP的机械通气天数，早发VAP短于晚发VAPICU3060性（5）。VAPVAP组的机械通气时间长于NON-VAP组机械通气天数，VAP组的住院天数也长于NON-VAPVAPNON-VAP3060（6）。讨论机械通气的使用为呼吸衰竭患者的生命支持提供了有力保障[7]。目前，呼吸机相关性肺炎已经成为ICU中最为常见的一种院内获得性感染，延长ICU中机械通气时间及ICU405060%[9]，而世界范VAP245076%[10]ICU20136201412327名机48h85例被诊断为VAP25.99%，住院54.12%，306041.1850.59%，和国内研究及之前国[3]VAP[11,12]。在本研究中我们还发现我院VAP的致病菌以革兰氏阴性杆菌为主，共有79株，占致病菌的82.30%，最常见的致病菌为：铜绿假单胞菌、鲍氏不动杆菌及肺炎克雷伯杆菌，它们分别占25.00%、21.8715.63%，三者均是常见的非发酵性G-杆菌，而金黄色葡萄球菌仅占7.29%，铜绿假单胞菌和鲍氏不动杆菌是我院综合ICU中VAPVAP致病菌前3[7][13]20012012年间ICU病房VAP分离出的致病菌以G-2007-20122001-2006VAP本研究VAP致病菌分布情况与国内及亚洲整体VAP[14VAP[15]VAP[16]。研究发现尽管VAP（Enterococcusfaecium,Staphylococcusaureus,Klebsiellapneumoniae,Acinetobacterbaumannii,PseudomonasaeruginosaandEnterobacterspecies,ESKAP是导致VAPVAP致病菌的80[17，本研究中以上六种致病菌共占VAP75%，并发现嗜麦芽寡养食单胞菌、粘质VAP丝酵母菌是气管插管患者下呼吸道常见的定植菌VAP假丝酵母菌6[1885VAP72为多重感124VAP[19]，这一差异可能与研究涉及人口统计学资料不同及我院采VAPVAP36（42.35%），共培养38VAP49共培养出58雷伯菌，说明我院ICU晚发型VAP比早发型VAP常见，无论是早发型VAP还是晚发型VAP，两者均是以G-[20]在探讨他们医院迟发型VAP主要致病菌分布情况时，3VAPVAP致病菌以肺炎克雷伯菌、鲍氏不动杆菌及铜绿假单胞菌居前3VAP3[21]早发型及晚发型VAPVAPVAPVAP患者感染及降低其病死率ICU常见致病菌及抗生素耐药性情况来选择合适抗生素[22]。VAP722.58VAP2441.38%，两组比较差异有统计学意义，说明与早发型VAPVAP[4[21]显示早发型VAP70.4%为VAP84VAPMDR比例均比我院的MDRVAP[4]。与早发型VAPVAP是早发型及晚发型VAPVAPVAPVAP比晚发型VAP患者病死率VAP性强及MDR[23]E.Bouza[24]发现MRSA感染所致VAP的患者比其他细菌导致VAP的患者拥有更高的病死率vs47%；P=0.02），并分析其原因可能与感染MRSA的VAPVAPMRSAVAPVAP的病死率较晚发VAP型及晚发型VAP最后，本研究观察了VAP对机械通气患者预后的影响，在对VAP组及NON-VAP组的预后ICU住院时间及病死率上存在的差异有统计VAP延长VAPICU[2]。本研究的不足之处在于其回顾性的本质VAP危险因素如患者意识状态ICUVAP所医院的综合ICUVAP参考文献[1]中华医学会重症医学分会.呼吸机相关性肺炎诊断、预防和治疗指南(2013).中华内科杂[1]中华医学会重症医学分会.呼吸机相关性肺炎诊断、预防和治疗指南(2013).中华内科杂志,2013,52(6):524-543.ChastreJ,FagonVentilator-associatedpneumonia.AmJRespirCritCareMed,2002,165(7):867-903.AmericanThoracicSociety.Guidelinesforthemanagementofadultshospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirAmericanThoracicSociety.Guidelinesforthemanagementofadultshospital-acquired,ventilator-associated,andhealthcare-associatedpneumonia.AmJRespirCareMed,2005,171(4):388-416.GiardM,LepapeA,AllaouchicheB,etal.Early-andlate-onsetventilator-associatedpneumoniaacquiredintheintensivecareunit:comparisonofriskfactors.JCritCare,2008,23(1):27-33.RestrepoMI,PetersonJ,FernandezJF,etal.Comparisonofthebacterialetiologyofearly-onsetandlate-onsetventilator-associatedpneumoniainsubjectsenrolledin2largeclinicalstudies.RespirCare,2013,58(7):1220-1225.杜煦.我院老年患者呼吸机相关性肺炎病原菌分布及药敏分析.临床肺科杂志,2013,18(5):840-842.SafdarN,DezfulianC,CollardHR,etal.Clinicalandeconomicconsequencesventilator-associatedpneumonia:asystematicreview.CritCareMed,2005,33(10):2184-2193..ICU学,2013,(2):310-311.ChastreJ,FagonJY.Ventilator-associatedpneumonia.AmJRespirCritCareMed,2002,165（7）:867-903.HunterJD.Ventilatorassociatedpneumonia.PostgradMedJ,2006,82(965):172-8.[12]MoreheadRS,Pinto SJ. Ventilator-associatedpneumonia.Arch InternMed 安立红,王红阳.ICU呼吸机相关性肺炎病原茵分布迁研究变.临床肺科杂志，2014,19(3):547-548.安立红,王红阳.ICU呼吸机相关性肺炎病原茵分布迁研究变.临床肺科杂志，2014,19(3):547-548.ChungDR,SongJH,KimSH,etal.Highprevalenceofmultidrug-resistantnonfermentersinhospital-acquiredpneumoniainAsia.AmJRespCritCareMed,2011;184(12):1409-1417.[15].Torres A, Carlet J. Ventilator-associated pneumonia. European Task Force ventilator-associatedpneumonia.EurRespirJ,2001,17(5):1034-1045.EnneVI,PersonneGrgicL,etal.Aetiologyofhospital-acquiredpneumoniaandtrendsinantimicrobialresistance.CurrOpinPulmMed,2014,20(3):252-258.SandiumengeA,RelloJ.Ventilator-associatedpneumoniacausedbyESKAPEorganisms:cause,clinicalfeatures,andmanagement.CurrOpinPulmMed,2012,18(3):187-193.HametM,PavonA,DalleF,etal.Candidaspp.airwaycolonizationcouldpromoteantibiotic-resistantbacteriaselectioninpatientswithsuspectedventilator-associatedpneumonia.IntensiveCareMed,2012,38(8):1272-1279.[19]CombesA,FiglioliniC,TrouilletJL,etal.Incidenceandoutcomeofpolymicrobial感染病杂志（电子版）,2013,7(1):96-99.GadaniH,VyasA,KarAK.Astudyofventilator-associatedpneumonia:Incidence,outcome,riskfactorsandmeasurestobetakenforprevention.IndianJAnaesth,2010,54(6):535-40.[22]KoulentiD,RelloJ.Gram-negativebacterialpneumonia:aetiologyandmanagement.感染病杂志（电子版）,2013,7(1):96-99.GadaniH,VyasA,KarAK.Astudyofventilator-associatedpneumonia:Incidence,outcome,riskfactorsandmeasurestobetakenforprevention.IndianJAnaesth,2010,54(6):535-40.[22]KoulentiD,RelloJ.Gram-negativebacterialpneumonia:aetiologyandmanagement.OpinPulmMed,2006,12(3):198-204.[23]SaravuK,PreethiV,KumarR,etal.Determinantsofventilatorassociatedpneumoniaanditsimpactonprognosis:Atertiarycareexperience.IndianJCritCareMed,2013,17(6):337-342.[24]BouzaE,GiannellaM,BunsowE,etal.Ventilator-associatedpneumoniaduetoJmeticillin-resistantStaphylococcusaureus:riskfactorsandoutcomeinalargegeneralhospital.HospInfect,2012,80(2):150-155.HospInfect,2012,80(2):150-155.表1 两组患者的一般资料Tab1Thecharacteristicsofthepatientsindifferentgroups变量 NON-VAP组年龄（岁，X性别年龄（岁，X性别±s）男性n（%）153(63.22)54(63.53)0.960女性n（%）89(36.78)22.62±6.7331(36.47)24.21±5.770.053APACHEII评分（分，X±s）原发疾病0.375肺部疾病64300.121神经系统疾病77260.834心血管疾病1340.812创伤及手术3560.076肿瘤1950.549肾脏疾病920.548血液疾病500.748肝胆胰疾病940.382糖尿病430.778其他750.589合计242850.121

VAP组(n=85)67.81±17.87

P值0.924注：VAP：呼吸机相关性肺炎；NON-VAP:非呼吸机相关性肺炎；APACHEII评分：急性生理及慢性健康状况评分II。表2 呼吸机相关性肺炎患者病原菌分布情况Table2ThedistributionofmicrobialaetiologyinVAPpatients病原菌 株数构成比（%）革兰氏阴性菌铜绿假单胞菌2425.00鲍氏不动杆菌2121.87肺炎克雷伯杆菌1515.63洋葱伯克霍尔德菌77.29粘质沙雷菌33.13嗜麦芽寡养单胞菌44.17阴沟肠杆菌22.08产酸及臭鼻克雷伯杆菌22.08保科爱德华菌11.04合计7982.29革兰氏阳性菌金黄色葡萄球菌1010.42真菌白假丝酵母菌66.2