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1、CostofHospitalStayAssociatedwithResistance第1页/共79页第一页，共80页。Nosocomial Infection in ICUNosocomial Infection in ICUanoverallriskof18%ofacquiringaninfectionduringICUstayoneofthemostcommoncausesofdeathinICUs第2页/共79页第二页，共80页。Nosocomial Infection in ICUNosocomial Infection in ICUEuropean Prevalence of Inf
2、ection in Intensive Care Study (EPIC)Held on April 29, 1992an overall of 9567 patientsfrom 1417 ICUs第3页/共79页第三页，共80页。EPIC DataEPIC Dataa total of 45% of patients had an infectionICU-acquired infection21%community-acquired infection14%hospital-acquired infection other than ICU10%第4页/共79页第四页，共80页。Noso
3、comialInfectionNosocomialInfectionVincentetal.JAMA1995;374:639-644(EPIC)Vincentetal.JAMA1995;374:639-644(EPIC)第5页/共79页第五页，共80页。Nosocomial Infection in ICUPredisposing risk factorsprolong length of ICU stayantibiotic usagemechanical ventilationurinary catheterizationpulmonary artery catheterizationce
4、ntral venous accessstress ulcer prophylaxisuse of steroidnutritional status第6页/共79页第六页，共80页。Nosocomial Infection in ICU第7页/共79页第七页，共80页。Nosocomial Infection in ICUUse of Antibiotics - EPIC dataof 10,038 patients, 62% received antibiotics for either prophylaxis or treatment第8页/共79页第八页，共80页。Nosocomial
5、 Infection in ICUPrevious exposure to antibioticsmodify intestinal flora, leading to colonization with resistant bacteria3rd generation cephalosporinsfluoroquinolonesvancomycinfavor the selection of inducible beta-lactamase producing GNB, such as Pseudomonoas aeruginosa, Enterobacter clocae, Serrati
6、a spp., and Citrobacter freundii第9页/共79页第九页，共80页。Nosocomial Infection in ICUCommon pathogens community-acquired infection and early ( 4d) hospital-acquired infectionsEnterobacter spp.Serratia spp.ESBL-producing microorganismsPseudomonas aeruginosaAcinetobacter spp.MRSAenterococcifungi第11页/共79页第十一页，共
7、80页。EPIC DataEPIC Datamost common pathogensS. aureus30%P. aeruginosa29%Coagulase-negative staphylococci19%E. coli13%Enterococcus spp.12%第12页/共79页第十二页，共80页。第13页/共79页第十三页，共80页。第14页/共79页第十四页，共80页。EmergingPathogensData from ICU, PUMCH 1999第15页/共79页第十五页，共80页。EmergingPathogens第16页/共79页第十六页，共80页。Mechanism
8、of Resistance to Beta-lactam AntibioticsDepartment of Critical Care MedicinePeking Union Medical College Hospital第17页/共79页第十七页，共80页。Principleofbeta-lactamactionarigidbacterialcellwallprotectsbacteriafrommechanicalandosmoticinsultbeta-lactaminhibitsPBPspreventingformationofthepeptidebridgesproducingw
9、eakenedwallactivatingcellwalldegradingenzymes-autolysinbeta-lactaminterfereswithnormalcellwallbiosynthesis,causingimpairedcellularfunction,alteredcellmorphologyorlysis第18页/共79页第十八页，共80页。MechanismofAntibioticResistance第19页/共79页第十九页，共80页。Doesbeta-lactamaseconferresistance?Theamountofenzymeproductsitsa
10、bilitytohydrolysetheantibioticinquestionitsinterplaywiththecellularpermeabilitybarriers第20页/共79页第二十页，共80页。InducibleBeta-lactamasealsocalledclassIbeta-lactamaseorconstitutivebeta-lactamaseorAmpCbeta-lactamasemostarechromosome-mediatedmajorproducersPseudomonasaeruginosaEnterobactersp.Citrobactersp.Ser
11、ratiasp.Morganellamorgannii第21页/共79页第二十一页，共80页。InducibleBeta-lactamasetransientelevationinbeta-lactamasesynthesiswhenabeta-lactamispresentenzymeproductionreturnstoalowlevelwhentheinducerisremovedlowlevelinsufficienttoprotectbacteriaevenagainstdrugsrapidlyhydrolysedbytheenzymesenzymehyperproducer=mut
12、antsthatproduceClassIenzymescontinuouslyatahighlevel第22页/共79页第二十二页，共80页。InducibleBeta-lactamaseInduction is lost within 4 to 6 hrs once the strong inducer is removed.Little need for concern if therapy with a strong inducer is discontinued and the drug replaced by a weak inducer.第23页/共79页第二十三页，共80页。A
13、ctivity of Drugs Against Organisms with Elevated Beta-Lactamase LevelsDecreased ActivityMonobactamsSecond-, Third-generation cephalosporinsBroad-spectrum penicillinsMaintain ActivityImipenem, MeropenemFourth-generation cephalosporinsCiprofloxacin, ofloxacin, etcSMZ/TMPco (except P. Aeruginosa)Aminog
14、lycosides第24页/共79页第二十四页，共80页。Antibiogram of Enterobacter第25页/共79页第二十五页，共80页。Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during TherapyChow JW, et alAnn Int Med 1991; 115: 585-90第26页/共79页第二十六页，共80页。MultiresistantEnterobacter*Antibiotics received in the 2 weeks be
15、fore the initial positive blood cultureAssociation of Previously Administered Antibiotics withMultiresistant Enterobacter in the Initial Blood Culture第27页/共79页第二十七页，共80页。MultiresistantEnterobacterEmergence of Resistance to Cephalosporin, Aminoglycoside, and Other Beta-Lactam Therapy* Cefotaxime, cef
16、tazidime, ceftriaxone, ceftizoxime* Gentamicin, tobramicin, amikacin, netilmicin* Imipenem, piperacillin, ticarcillin, aztreonam, mezlocillin, ticarcillin-clavulanate第28页/共79页第二十八页，共80页。MultiresistantEnterobacterFactors Associated with Mortality in Patients with Enterobacter Bacteremia第29页/共79页第二十九页
17、，共80页。Extendedspectrumbeta-lactamaseMostareplasmidmediated1to4aminoacidchangesfrombroad-spectrumbeta-lactamases,thereforegreatlyextendingsubstraterangeMajorproducersE.Coli(TEM)Klebsiellasp.(SHV)inhibitedbybeta-lactamaseinhibitors第30页/共79页第三十页，共80页。Reliable (relatively) agents for ESBL-producing path
18、ogensCarbapenemsAmikacinCephamycins (except MIR-1 type; 30% of strains)Beta-lactamase inhibitorspip/tazo 30% R in Chicago 199626% R in ICU, PUMCH 1999第31页/共79页第三十一页，共80页。Antibiogram of E. coli第32页/共79页第三十二页，共80页。Antibiogram of Klebsiella第33页/共79页第三十三页，共80页。PrevalenceofCAZ-RKlebsiellaFrom Itokazu G,
19、et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patientsClinical Infectious Diseases 1996; 23: 779-85第34页/共79页第三十四页，共80页。Cross-ResistanceinCAZ-RKlebsiellaFrom Itokazu G, et al. Nationwide Study of Multiresistance Among Gram-Negative Bacilli from ICU patientsClinical I
20、nfectious Diseases 1996; 23: 779-85第35页/共79页第三十五页，共80页。PrevalenceofESBLData from Intensive Care Unit, Peking Union Medical College Hospital, 1999第36页/共79页第三十六页，共80页。Cross-ResistanceinCAZ-RKlebsiellaData from Intensive Care Unit, Peking Union Medical College Hospital, 1995-1999第37页/共79页第三十七页，共80页。Eff
21、ectofESBLonMortalityAnalysis of mortality in 216 bacteremic patients caused by Klebsiella pneumoniaePatterson et al. 37th ICAAC, 1997, Abstr J-210第38页/共79页第三十八页，共80页。EffectofESBLonMortalityPatterson et al. 37th ICAAC, 1997, Abstr J-210Empiric antibiotic therapy in 32 bacteremic patients caused by ES
22、BL-positive Klebsiella pneumoniae第39页/共79页第三十九页，共80页。Molecular Epidemiology of CAZ-R E. Coli and K. Pneumoniae Blood IsolatesSchiappa D, et alRush University and University of Illinois, Chicago ILJournal of infectious Diseases 1996; 174: 529-37第40页/共79页第四十页，共80页。RiskFactorsforCAZ-RKlebsiellaBacterem
23、ia第41页/共79页第四十一页，共80页。CAZ-RKlebsiellaBacteremia* Outcome of Patients with CAZ-R Bacteremia Who Received Appropriate vs. Inappropriate Therapy Within 72 Hours of Bacteremic Event第42页/共79页第四十二页，共80页。Ceftazidime-emergenceofresistanceEmergenceofAntibiotic-ResistantPseudomonasaeruginosa:ComparisonofRisks
24、AssociatedwithDifferentAntipseudomonalAgentsbyCarmeliY,etal.AntimicrobialAgentsandChemotherapy1999;43(6):1379-82第43页/共79页第四十三页，共80页。Ceftazidime-emergenceofresistancea320-bedurbantertiary-careteachinghospitalinBoston,Mass.11,000admissionsperyear4studyagentswithantipseudomonalactivityceftazidime,cipro
25、floxacin,imipenem,piperacillinatotalof271patients(followedfor3,810days)withinfectionsduetoP.Aeruginosaweretreatedwiththestudyagentsresistanceemergencein28patients(10.2%),withanincidenceof7.4per1,000patient-days第44页/共79页第四十四页，共80页。Ceftazidime-emergenceofresistanceTable. Multivariable Cox hazard model
26、s for the emergence of resistance to any of the four study drugs第45页/共79页第四十五页，共80页。ClassificationofAntibioticTherapyProphylacticUseTherapeuticUseEmpirictherapyDefinitivetherapy第46页/共79页第四十六页，共80页。Empiric Antibiotic TherapyDepartment of Critical Care MedicinePeking Union Medical College Hospital第47页
27、/共79页第四十七页，共80页。EmpiricAntibioticTherapyWhentreatingseriouslyillpatientswhoareatriskofdevelopingsepticshockwhenpathogensareunknownornotconfirmedantibioticselectionaccordingtoepidemiologyofNIinthewardresistanceprofileofmostcommonpathogens第48页/共79页第四十八页，共80页。EmpiricAntibioticTherapySearchingforinfecti
28、onfocuscollectingsamplesforculturestartingempiricantibiotictherapyassoonaspossiblereferringtodefinitiveantibiotictherapyassoonaspossible第49页/共79页第四十九页，共80页。AntibioticTherapyandPrognosisObjective:ToevaluatetherelationshipbetweentheadequacyofantibiotictreatmentforBSIandclinicaloutcomesamongICUptsDesig
29、n:ProspectivecohortstudySetting:AmedicalICU(19beds)andasurgicalICU(18beds)fromauniversity-affiliatedurbanteachinghospitalPatients:492ptsfromJuly1997toJuly1999Intervention:None第50页/共79页第五十页，共80页。AntibioticTherapyandPrognosis147(29.9%)ptsreceivedinadequateantimicrobialtreatmentfortheirBSIThemostcommon
30、lyidentifiedbloodstreampathogensandtheirassociatedratesofinadequateantimicrobialtreatmentincludedvancomycin-resistantenterococci(n=17;100%)Candidaspecies(n=41;95.1%)MRSA(n=46;32.6%)SCoN(n=96;21.9%)Pseudomonasaeruginosa(n=22;10.0%)第51页/共79页第五十一页，共80页。AntibioticTherapyandPrognosisHospitalmortalityrate
31、ptswithaBSIreceivinginadequateantimicrobialtx(61.9%)ptswithaBSIreceivingadequateantimicrobialtx(28.4%)(RR,2.18;95%CI,1.77to2.69;p0.001)Independentdeterminantofhospitalmortalitybymultiplelogisticregressionanalysisadministrationofinadequateantimicrobialtx(OR,6.86;95%CI,5.09to9.24;p0.001)第52页/共79页第五十二页
32、，共80页。AntibioticTherapyandPrognosisIndependentpredictoroftheadministrationofinadequateantimicrobialtxbymultiplelogisticregressionanalysisBSIattributedtoCandidaspecies(OR,51.86;95%CI,24.57to109.49;p0.001)prioradministrationofantibioticsduringthesamehospitalization(OR,2.08;95%CI,1.58to2.74;p=0.008)dec
33、reasingserumalbuminconcentrations(1-g/dLdecrements)(OR,1.37;95%CI,1.21to1.56;p=0.014)increasingcentralcatheterduration(1-dayincrements)(OR,1.03;95%CI,1.02to1.04;p=0.008)第53页/共79页第五十三页，共80页。InappropriateempiricantibiotictherapyObjective:toassesstheincidence,risk,andprognosisfactorsofNPacquiredduringm
34、echanicalventilation(MV)Settingsa1,000-bedteachinghospitalApril1987throughMay1988Patients78(24%)episodesofNPin322consecutivemechanicallyventilatedpatients第54页/共79页第五十四页，共80页。InappropriateempiricantibiotictherapyFrom: Torres et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mec
35、hanically ventilated patients. Am Rev Respir Dis 1990 Sep;142(3):523-8第55页/共79页第五十五页，共80页。DifficultyinempiricantibiotictherapyObjective:ToassessthefrequencyofandthereasonsforchangingempiricantibioticsduringthetreatmentofpneumoniaacquiredinICUDesign:Aprospectivemulticenterstudyof1yearsdurationSetting
36、:MedicalandsurgicalICUsin30hospitalsalloverSpain.Patients:Ofatotalof16,872patientsinitiallyenrolledintothestudy,530patientsdeveloped565episodesofpneumoniaafteradmissiontotheICU.第56页/共79页第五十六页，共80页。DifficultyinempiricantibiotictherapyEmpiricantibioticsin490(86.7%)ofthe565episodesofpneumoniaThemostfre
37、quentlyusedantibioticsamikacin120casestobramycin110ceftazidime96cefotaxime96Monotherapyin135(27.6%)ofthe490episodesCombinationof2antibioticsin306episodes(62.4%)Combinationof3antibioticsin49episodes(10%)第57页/共79页第五十七页，共80页。DifficultyinempiricantibiotictherapyTheempirictxmodifiedin214(43.7%)casesisola
38、tionofamicroorganismnotcoveredbytreatment133(62.1%)caseslackofclinicalresponse77(36%)developmentofresistance14(6.6%)Individualfactorsassociatedwithmodificationofempirictreatmentidentifiedinthemultivariateanalysismicroorganismnotcovered(RR22.02;95%CI11.54to42.60;p0.0001)administrationofmorethanoneant
39、ibiotic(RR1.29;95%CI1.02to1.65;p=0.021)previoususeofantibiotics(RR1.22;95%CI1.08to1.39;p=0.0018)第58页/共79页第五十八页，共80页。DifficultyinempiricantibiotictherapyCompared with appropriate empiric therapy, inappropriate therapy was associated withhigher mortality (p=0.0385)more complications (p0.001)higher inc
40、idence of shock (p38Cor10,000or3,000)purulentbronchialsecretionsInterventions:BronchoscopywithBALwithin24hofclinicaldxofVAPorprogressionofaninfiltrateduetopriorVAPorNPAllpatientsreceivedantibiotics,107priortobronchoscopyand25immediatelyafterbronchoscopy.第61页/共79页第六十一页，共80页。Difficultyinempiricantibio
41、tictherapyFrom: Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C, Matera J, Jolly EC. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997 Mar;111(3):676-85 第62页/共79页第六十二页，共80页。DifficultyinempiricantibiotictherapyFrom: Kollef MH, Ward S The influence of mi
42、ni-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest 1998 Feb;113(2):412-20第63页/共79页第六十三页，共80页。Hospital Infection ControlDepartment of Critical Care MedicinePeking Union Medical College Hospital第64页/共79页第六十四页，共80页。ScheduledChangeso
43、fEmpiricAntibioticTherapyObjective:Todeterminetheimpactofascheduledchangeofabxclasses,usedfortheempirictxofsuspectedgram-negativebacterialinfections,ontheincidenceofVAPandnosocomialbacteremiaPatients:680patientsundergoingcardiacsurgerywereevaluatedIntervention:Duringa6-moperiod(i.e.,thebefore-period
44、),ourtraditionalpracticeofprescribinga3rdgenerationcephalosporin(ceftazidime)fortheempirictxofsuspectedgram-negativebacterialinfectionswascontinuedThiswasfollowedbya6-moperiod(i.e.,theafter-period)duringwhichaquinolone(ciprofloxacin)wasusedinplaceofthethird-generationcephalosporin.第65页/共79页第六十五页，共80
45、页。ScheduledChangesofEmpiricAntibioticTherapyFrom: Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 1997 Oct;156(4 Pt 1):1040-8 第66页/共79页第六十六页，共80页
46、。NosocomialInfectionControlScheduledchangesofantibioticclassesforempirictreatmentofsuspectedordocumentedGNBinfectionsTimeperiod1(n=1323)ceftazidimeTimeperiod2(n=1243) ciprofloxacinTimeperiod3(n=1102)cefepime第67页/共79页第六十七页，共80页。NosocomialInfectionControlScheduledchangesofantibioticclassestargetedatth
47、eempirictreatmentofgram-negativebacterialinfectionscanreducetheoccurrenceofinadequateantimicrobialtreatmentofnosocomialinfectionsreducingtheadministrationofinadequateantimicrobialtreatmentforpatientswithanAPACHEII15canimprovehospitalsurvivalFrom Kollef MH. The clinical impact of scheduled antibiotic
48、 class changes for the empiric treatment of nosocomial gram-negative bacterial infections in the intensive care unit (ICU) setting. Abstracts of 39th ICAAC 1999: 594第68页/共79页第六十八页，共80页。Evaluation of Clinical Practice Guidelines on Outcome of Infection in Patients in the Surgical Intensive Care UnitP
49、rice J, et alCritical Care Medicine 1999; 27: 2118-24第69页/共79页第六十九页，共80页。BackgroundWilliamBeaumontHospitalRoyalOak,Michigan929-bed,community-basedteachinghospitalnewlyconstructedSICUwith20privateroomspathogenshighlyresistantto3rd-generationcephalosporins第70页/共79页第七十页，共80页。ClinicalPracticeGuideline-e
50、mpiricantibiotics第71页/共79页第七十一页，共80页。Clinical Practice Guideline - empiric antibiotics第72页/共79页第七十二页，共80页。Clinical Practice Guideline - empiric antibiotics第73页/共79页第七十三页，共80页。ClinicalPracticeGuidelineStudyDesignprospectiveanalysisofallICUpatientsphaseI51daysbeforeguidelineimplementationinterveningpe
51、riod8mthsguidelineimplementationphaseII34daysafterguidelineimplementation第74页/共79页第七十四页，共80页。ClinicalPracticeGuideline-ClinicalOutcome第75页/共79页第七十五页，共80页。Clinical Practice Guideline -Clinical Outcome第76页/共79页第七十六页，共80页。HandwashingandDisinfectionOutbreaksareoftenrelatedtofailureininfectioncontroltech
52、niquesordisregardforinfectioncontrolguidelinesThemostcommonmodeoftransmissionisthehandsofahealth-careworkerHandwashing=effectivelypreventhorizontaltransmissionofinfectionsCompliancewithhandwashingpoliciesseldomexceeds40%第77页/共79页第七十七页，共80页。HandwashingandDisinfectiona: ICU beds 12; Nurses/shift 3; Wo
53、rking hours/shift 8; Patient contacts/hr 5; 12X3X8X5X2 min (0.5 min)b: Nursing time lost/8 hr shift = 48/8第78页/共79页第七十八页，共80页。感谢您的观看(gunkn)！第79页/共79页第七十九页，共80页。内容(nirng)总结Cost of Hospital Stay Associated with Resistance。community-acquired infection14%。P. aeruginosa29%。Coagulase-negative staphylococci19%。E. coli13%。Enterococcus spp.12%第八十页，共80页。
