Journal club present at :

KHON KAEN HOSPITAL

Empiricantibiotictherapyforsuspected
ventilatorassociatedpneumonia:
Asystematicreviewandmetaanalysis
ofrandomizedtrials

 (Database)

(https://vpn.kku.ac.th/library/,DanaInfo=www.library.kku.ac.th+main.php)

Databases=>MEDLINE/Pubmed
Keywordssearch :
"Pneumonia,VentilatorAssociated/drugtherapy"[Mesh]
OR"Pneumonia,Ventilator
Associated/mortality"[Mesh]OR"Pneumonia,
VentilatorAssociated/therapy"[Mesh])

 (Database)

Impactfactor:
CriticalCareMedicine:
January2008 Volume36
Issue1 pp108117
ImpactFactor=6.594

 :
MaryAnneW.Aarts (MD,MSc,FRCSC)
WyethAyerst FellowshipinClinicalandEvaluativeSciencesof
theSurgicalInfectionSociety

DarenHeyland (MD,MSc,FRCPC) honoraria

grantfundingAstra ZenecaBayer

JohnC.Marshall(MD,FRCSC) Wyeth,
Astra Zeneca,LEOPharma,Hutchinson,EisaiBecton
Dickinson, speakingfeesPfizer funding
GlaxoSmithKline

Introduction:
Ventilatorassociatedpneumonia(VAP)
ICU
mechanicalventilation>24hrs
ICU57
VAP,Clinicalcriterianonspecific,
sensitivity

Guidelinesrecommend empirical
antimicrobialtherapy

Introduction( ) :
EarlyVAP communityacquired
pneumonia Haemophilus influenzae,
StreptococcuspneumoniaeStaphylococcus
aureus
LateVAP VAP antibiotics
multiresistant organisms
Pseudomonasspp,Acinetobactermethicillin
resistantS.aureus

Introduction( ) :
RecommendationsforempiricaltreatmentVAP
EarlyVAP : singleagentceftriaxone,ampicillin/
sulbactam fluoroquinolone
LateVAP : carbapenem , carbapenem+vancomycin ,
combinationtherapy aminoglycoside ciprofloxacin
antipseudomonal penicillin,lactam/lactamase
inhibitorcombination,ceftazidime cefepime

Introduction( ) :
Combinationtherapeuticsuccess
extendedspectrumofactivity,antimicrobial
synergy,potential microorganisms
:combination
therapy,toxic broadspectrum
therapy multiresistant organisms
,superinfectionsdeath

Objective:
availableevidence
RCTparenteral
antibioticregimens
monotherapycombinationtherapy
empiricalsuspectedVAP

MaterialandMethods
Trialstudy:systematicreviewandmetaanalysisof
randomizedtrials

ResearchProtocal :DepartmentofSurgery,Health
PolicyManagementandEvaluation,CriticalCare
MedicineUniversityofToronto,Departmentof
MedicineandQueensUniversityKingstonOntario

:.. 19842006

MaterialandMethods

MaterialandMethods
2groupindependent reviewabstracts
SearchSources:
Medline(19662007)
EMBASE(19802007)
CochraneCentralRegisterofControlledTrials

SearchTerm:
ventilatorassociatedpneumonia, ventilators,mechanical,
orrespiration,artificial combinedwithcrossinfection, or
pneumonia, andcrossedwithantibacterialagents

MaterialandMethods
Text/titlewords Trial
RCTreview
articles
Bibliographiesreviews,studies
searched
Trials experts
authorsidentifiedtrials

MaterialandMethods
Inclusioncriteria:
RCTs ofempiricaltreatmentforVAP parenteral
antibioticregimenplacebo parenteral
antibiotic
suspectVAP
ventilater>48., ,leukocytosis,purulentsecretions
Exclusioncriteria:
patientsTrials<50% (ventilater)
initiationantibiotics.

MaterialandMethods
Outcome:
Primaryoutcome:
Mortality2830

Secondaryoutcomes:
treatmentfailure(signs/symptomspneumonia )
 seriousadverseevents(seizures,pseudomembranous
colitis,nonreversibleendorgandamage)
 superinfections (new,persistent,signs new
pathogenorsimilarpathogensensitivityantibiotic
,

MaterialandMethods
2reviewgroups
(extracteddataandassessedquality)

Record
 participants
 participatingsites country

 duration
 Experimental&controlantibioticregimens
 microbiological
 clinicalresponsefinancialsupport

MaterialandMethods
Qualityoftrials
Doubleblinded(physiciansandpatients)
GroupAssignmentConcealedblindedassessor

Trial initiallyenrolled
intentiontotreat(ITT)analysis
samplesizeTrial

MaterialandMethods
Outcomedata
ITTanalysisclinicalefficacy
empiricalantibioticregimens
monotherapyCombinetherapy
sensitivitypooledtrials
doubleblindedmethodology ,blinded
assessmentofoutcome,concealedgroupallocation
completefollowupofenrolledpatients.
 trials

MaterialandMethods
Dichotomousoutcomes
Relativerisks(RR)

with95%confidenceintervals(CI)
Arandomeffectsmodelpooledoutcomes
DerSimonianLairdmethod
Outcomesweightedinversevariance
RevMan,version4.2forWindows
Copenhagen:TheNordicCochraneCentre,
TheCochraneCollaboration,2003)

Results:
1.Diagramprocessforidentifyingtrals

2. Characteristicsandqualityoftrialscomparing
antibiotictherapiesforVAP
3.Ratesoftreatmentfailureinpooledtrialscomparing
specificantibioticregimens
4. Mortalityinpooledtrialscomparingmonotherapy to
combinationtherapy
5.Treatmentfailureinpooledtrialscomparing
monotherapy withcombinationtherapy

Results:
Exclude103trials
Nonparenteral antibiotics
Prophylacticantibiotic
Communityacquiredinfection
Add8trials
Bibliography
reviewandauther
Exclude18trials
13trials(, ventilater )
2trialsnosocomial pneumonia
2trialsDuplicate
1trialnotrandomized

Figure1:diagram 41trials

Table1.Characteristicsandqualityoftrialscomparingantibiotic
therapiesforventilatorassociatedpneumonia(VAP)

Figure2.Mortalityinpooledtrialscomparingspecificantibioticregimens

evidence
regimen
RR1=>Nosignificant!!
mortalityrate20.3%

Figure3.Ratesoftreatmentfailureinpooledtrialscomparing
specificantibioticregimens

RR 1=>Significant!!

Figure4.Mortalityinpooledtrialscomparingmonotherapy
tocombinationtherapy

evidence combine therapy

monotherapy
No significant !!

Figure5.Treatmentfailureinpooledtrialscomparing
monotherapy withcombinationtherapy

evidence Treatment failure

combination therapy monotherapy
No significant !!

Discussion:
Findings:

metaanalysis resultspower
empiricalantimicrobialtherapy
suspectedVAP
mortalityantibioticregimens

evidence combinationtherapy
treatmentfailure superinfection
adverseevents monotherapy
specificempiricalregimens meropenem
Treatmentfailure ceftazidime
aminoglycosidemortality

Discussion( ) :
Findings:


regimens
treatmentfailure 5%
(errorItype) = 0.05
trials
clinical
pneumonia

sensitivity

Discussion( ) :
Limitations:
diluteimpact
antibioticregimens
VAP


review

Discussion( ) :
Previousstudies:
meta
analysis lactam
aminoglycoside -lactam
severesepsis

Furtherstudy:

Metaanalysis RCTs
,duration
,identificationpathogenutility
early empiricalantibiotic
therapy


:
Empiricalantibiotictherapy
combinational
therapy clinicaloutcome
monotherapysuspectVAP
Antibioticregimen
VAP regimen

(Savecost)

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