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AnOfficialPublicationofthePhilippineAcademyofPediatricPulmonologists,Inc.
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PAPPPERSPECTIVE
Updates
inthe
EvaluationandManagementof
PediatricCommunity-AcquiredPneumonia
PAPPTaskForceonpCAP[2008]
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PhilippineAcademyofPediatricPulmonologists,Inc.[PAPP,Inc.]2008
Allrightsreserved.PublicationandrequestforpermissiontoreproducecanbeobtainedfromthePhilippineAcademyofPediatricPulmonologists,Inc.,Room102GJBuilding,385QuezonAvenueQuezonCityTelefaxNo+6323747201;email:[email protected].
Thisdocumentisnotintendedtobeastandardofcare.Theresponsibilityforitsuselieswiththereader.InnoeventshallPAPP,Inc.beliablefordamagesarisingfromitsuse.
PAPPOfficers OliviaC.Go,MDFPPSFPAPP.President
ArnelGeraldQ.Jiao,MDFPPSFPAPP....Vice-President
CesarM.Ong,MDFPPSFPAPP...Secretary
MariaNerissaA.deLeon,MDFPPSFPAPP....Treasurer
MaryThereseM.Leopando,MDFPPSFPAPP.Director
ClaraR.Rivera,MDFPPSFPAPP.Director
MaryAnnF.Aison,MDFPPSFPAPP...Director
PAPPTaskForceonpCAPCristanQ.Cabanilla,MDFPPSFPAPP
ChairReginaM.Canonizado,MDFPPSFPAPPAnjanetteR.deLeon,MDDPPSDPAPPRoslynMarieK.Dychiao,MDFPPSDPAPPBeatrizPraxedesApollaI.Mandanas-Paz,MDDPPSDPAPPAnnaMarieS.Putulin,MDFPPSFPAPPEmilyDoloresG.Resurreccion,MDFPPSFPAPPAnaMariaA.Reyes,MDFPPSFPAPPMarionO.Sanchez,MDDPPSDPAPPRitaMarieLourdesS.Vergara,MDFPPSFPAPPRozaidaR.Villon,MDFPPSFPAPP
MembersGerardoL.Beltran,MDFPCR
GuestRadiologistGladysL.Gillera,MDDPPSDPAPP
Secretary
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CONTENTS
Foreword
PrefacetotheUpdatesandAcknowledgement
2004ClinicalPracticeGuidelineClinicalQuestionswithRecommendations,andUpdateHighlightswithAnnotations
Appendix
Bibliography
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FOREWORD
Inthepastyears,wewitnessedamajorrevolutioninthescienceandpracticeofpediatricpulmonarymedicine,moreparticularlyinourconceptandmanagementofpneumoniainchildren.Wearechallengedtoadoptandapplythesenewerinsightsaboutthediseaseindealingwithourpatients.
Despite the inadequate and limited advancement in medical
technology amongdeveloping countries, we are able to establish the
diagnosis of pneumonia and manage
itcomprehensivelylargelybasedongoodclinicalacumen.Furthermore,ourknowledgeinclinicalepidemiology
is imperative to facilitate its holistic management, while the
rational use ofantimicrobial agents increases our awareness on the
emergence of drug resistance in specificlocalities.
Thisclinicalupdateonpneumoniacontainsacomprehensiveevidence-based
reviewofnational as well as international researches that depicts
the current clinical practice andmanagement strategies adopted to
contain the disease. The Academy maintains its primarypurpose
toappriseourpediatricpractitionersof
themanymedicalinvestigationsonpneumoniaandproposepracticaltreatmentoptionstocombatthedisease.
Thiscurrentissuedoesnotintendtoreplacethe2004PPSClinicalPracticeGuidelineinthe
Management of Pediatric Community-Acquired Pneumonia. This is
simply presented toclarify some gaps in the knowledge stated
therein. We look forward that this
understandingbridgesthesmalldifferencesinourdailypracticetobringforthaworthyclinicaloutcome.
AllowmetotakethisgoodopportunitytocongratulatetheTaskForceonPCAPforsuchanexcellentjob.
OliviaC.Go,MDPresidentPhilippineAcademyofPediatricPulmonologists,Inc.
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PREFACETOTHEUPDATES
Oneof the issues thatwas raised regarding
the2004ClinicalPracticeGuideline in theEvaluation and Management of
Pediatric Community-Acquired Pneumonia is the gap inknowledge
underscored in each recommendation. To address this concern, the
Task Force
onpCAPhasrevieweddataavailablefromlocalandforeignliterature.Asthismanuscriptismerelyanupdateconsistingofrecentliterature,itisnotintendedtobeastandardofcaremuchmorearevisionofthecurrentguideline.
This update is available in two formats. The abbreviated format
consists of
updatehighlightsandsummaryofrecentevidence.Thisismadeavailableasalimitedserviceitemintheformofhardcopyduringthe200816thPAPPAnnualConvention.Thecompleteversionwhichincludesnotonlysimilarhighlightsbutdetaileddescriptionofeachupdatecanbedownloadedfrom
the Philippine Academy of Pediatric Pulmonologists, Inc. through
the website of thePhilippine Pediatric Society www.pps.org.ph. The
reader is encouraged to access the
completeversionforamorethoroughdiscussion.
CristanQCabanilla,MDChairTaskForceonpCAP
Acknowledgement
ThismanuscriptistheresultofaconcertedeffortbytheTaskForceonpCAPundertheleadershipandguidanceofthePAPPofficersheadedbyOliviaC.Go.SpecialgratitudeisduetoLuisM.RiveraSr.,AlexanderO.Tuazon,MilagrosS.BautistaandAgnesR.Mendozaforreviewingthedocument.
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2004CLINICALPRACTICEGUIDELINECLINICALQUESTIONSWITHRECOMMENDATIONS,AND
UPDATEHIGHLIGHTSWITHANNOTATIONS
ClinicalQuestions[CQ]
Evaluation
1.Whoshallbeconsideredashavingcommunity-acquiredpneumonia?2.Whowillrequireadmission?3.
Whatdiagnosticaidsareinitiallyrequestedforambulatorypatients?4.
Whatdiagnosticaidsareinitiallyrequestedforin-patients?
Treatment
5.Whenisantibioticrecommended?6.Whatempirictreatmentshouldbeadministeredifabacterialetiology
isstronglyconsidered?7.
Whattreatmentshouldbeinitiallygivenifaviraletiology
isstronglyconsidered?8.Whencanapatientbeconsideredasrespondingtothecurrent
antibiotic?9.Whatshouldbedoneifapatientisnotrespondingtocurrent
antibiotictherapy?10.Whencanswitchtherapyinbacterialpneumoniabestarted?11.Whatancillarytreatmentcanbegiven?
Prevention
12.Howcanpneumoniabeprevented?
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INTRODUCTION
Theworldincidenceoflowerrespiratorytractinfectionthatincludespneumoniain
developing countries has been recently estimated to be 150.7
million cases, 95%
ofwhomareunderfiveyearsofage,and13%severeenoughtorequirehospitaladmission[Rudan
I,2004]. In the Philippines, it continues to be a leading cause of
morbidity
inchildrenaccountingtoabout828.8per100,000population[DepartmentofHealthFieldHealthServiceInformationSystem,2006].
Estimates of treatment cost highlight the economic burden that
childhoodpneumonia places on health care systems. An average cost
of treatment for acuterespiratory
infectionperepisodefromtheperspectiveofdevelopingeconomies
inAsiarangedfromUSD1.70 inaprimaryhealthcare setting
toUSD155.30forhospitalizedcare [Toan NV,2001; Rattanadilok N,2002].
Outpatient and hospitalized care of a child
withpneumoniahavebeenestimatedtobeUSD13.44andUSD71.0perepisode,respectively[HussainH,2006].
Anaverageparents totalhouseholdexpenses forachildsadmissionbecause
of pneumonia have been found to be 5 to 11% of an average net
income perfamily in Israel [Shoham Y,2005]. In the local setting
asprovidedby
theNationalHealthInsuranceProgram,the2006totalpaymentclaimsforpneumonia[ICD-10CodeJ18.9]below19yearsofageamountedtoPhP324.688M[PhilippineHealthInsuranceCorporation,ClaimsPaymentSummaryforCY2006Ages0-19forPneumonia,2007].
One public health strategy to address this continuing concern is
theimplementationofaclinicalpracticeguideline.In2004,thePhilippinePediatricSociety,thePhilippineAcademyofPediatricPulmonologistsandthePediatricInfectiousDiseaseSocietyof
thePhilippines cameoutwith a clinical practice guideline in the
evaluationand management of pediatric community-acquired pneumonia.
In 2006, the
PhilippineHealthInsuranceCorporationhasadoptedthedocumentasoneoftheguidelinesthatcanserve
as a basis for quality assurance and accreditation [PhilHealth
Health
TechnologyAssessmentUnit,QualityAssuranceResearchandPolicyDevelopmentGroup,2006].Itsacceptabilityand
utilization have been subsequently assessed. Of the 166 respondents
to a
randomsamplingquestionnairesurveyconductedduringthe200643rdPPSAnnualConvention,82%acknowledgedapplying
the recommendation in their practice [Cabanilla C, Santos
J,2006].Inanothersurveyamong61pediatricconsultantsandresidentsfromMetroManila,about96%confirmedthatsuchguidelinewasbeingfollowed[deJesus-OabelBAandAtienza-deLeonMN,2007].
Thisupdatepresentsevidencesbasedonrecentlocalandforeignliteraturedealingwiththerecognitionofcommunity-acquiredpneumoniainanimmunocompetentpatientaged
2 months to 19 years, identification of appropriate and practical
diagnosticprocedures,andinitiationofrationalmanagementandpreventivemeasures
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CQ1.Whoshallbeconsideredashavingcommunity-acquiredpneumonia?
2004ClinicalPracticeGuidelineRecommendation
Predictorsofcommunity-acquiredpneumoniainapatientwithcough
1.forages3monthsto5yearsaretachypneaand/orchestindrawing[GradeB].
2.forages5to12yearsarefever,tachypnea,andcrackles[GradeD].
3.beyond12yearsofagearethepresenceofthefollowingfeatures[GradeD]:
a.fever,tachypnea,andtachycardia;and
b.atleastoneabnormalchestfindingsofdiminishedbreathsounds,rhonchi,cracklesorwheezes.
UPDATEHIGHLIGHTS
1.
Apatientpresentingwithahistoryofcoughand/orrespiratorydifficultyshouldbeevaluatedforthepossiblepresenceofpneumonia.However,thelackofcough
does not necessarily imply the absence of the disease as it may not
bepresent as an initial presentation in24%of caseswith
radiographicpneumonia.Thisisparticularlytrueintheyoungeragegroup.
2.
Therearephysicalsignsthatareusefultopredictthepresenceofpneumoniausingchestxrayasreferencestandard.Infourstudiesinvolvingchildrenbelow5yearsold,age-specifictachypneaasdefinedbytheWorldHealthOrganization[WHO]remainstobethebestsinglepredictor.Anotherusefulsinglephysicalsignisthepresenceofchestindrawing.Acombinationoftachypneaandchestindrawingprovidesahigherprobabilityasto
thepresenceofpneumonia. Inone study, the combinationof tachypnea,
lowoxygen saturation on admission and nasal flaring gave the
highest
predictivevalueamongallothersignsandsymptoms.Intwostudiesdealingwithpatientsolderthan5years,tachypneaalone,orincombinationwithfeverandcracklesarereliablepredictors.
3.
Theabsenceofeitherage-specifictachypneaasdefinedbyWHOorchestindrawingdoesnotruleoutthepresenceofpneumonia.
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Annotation1A.Background.
1. The Task Force on pCAP adopted the recommendation as provided
by theInternational Union Against Tuberculosis and Lung Disease
that pneumonia should beone of the considerations in a child with
acute illness presenting with either cough
ordifficultyofbreathing[EnarsonP,2004].However,itisimportanttonotethatcoughmaynotbenecessarilypresent,asitwasnotedtobeabsentasaninitialpresentationin24%ofradiologic
pneumonia [Taina Juven, 2003]. This phenomenom has been observed to
bemostcommonintheyoungeragegroup.
2.Basisforestablishingclinicalpredictors
a.
Forthepurposeofsearchingrelevantliteratureindeterminingtheclinicalpredictors
for pneumonia, the Task Force on pCAP has agreed to
considerradiographic findings as the benchmark in defining the
presence or absence ofchildhoodpneumonia.
b.
Acknowledginginter-observervariabilityinanalyzingchestx-raystudies[Swingler
GH, 2001], the World Health Organization has standardized
theradiographic interpretation of a child with pneumonia [World
Health
OrganizationPneumoniaVaccineTrialInvestigatorsGroup,2001].Usingthisstandard,thevariabilityhas
considerably improved, with a kappa index for the presence of
alveolarconsolidationat>0.60[CherianT,2005],and0.70(95%CI0.560.83)
[CastroAV,2006].
Annotation1B.Clinicalpresentationpredictiveofradiographicpneumonia
a.Thereisone[1]studydealingwithidentifyingpatientswithradiographicpneumoniaintheout-patientdepartment
Among1932patientsaged2-59months,coughandtachypnea,anddifficultyofbreathingandtachypneahadarelativerisk[RR]of1.18(95%CI0.41-3.43)and0.80(95%CI0.56-1.13),respectively.[HazirT,2006].
b.Thereisone[1]studydealingwithidentifyingpatientswithradiographicpneumoniainthecombinedout-patientdepartmentandemergencyroom
Among181patientsaged3monthsto5years,coughof5daysdurationwith
tachypneahas a+LR [orpositive likelihood ratio]of2.4 (95%CI1.5-3.8)
and LR [or negative likelihood ratio] of 0.27 (95% CI 0.19-0.39);
chest indrawing +LR of 8.7 (95% CI 1.3-62.4) and LR of
0.77(95%CI0.70-0.85); fever+LRof1.3(95%CI1.1-1.7)andLRof0.26(95% CI
0.13-0.51); crackles +LR of 3.1 (95% CI 1.8-5.3) and LR of
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0.15 (95% CI 0.09-0.25); and combination of tachypnea and
chestindrawing+LRof9.1(95%CI1.2-64.1)andLRof0.76(95%CI0.69-0.84)*[delaCruzR,2007].
c.Therearefive[5]studiesdealingwithidentifyingpatientswithradiographicpneumoniaintheEmergencyRoom
Among207patientsaged5-12yearsold,thecombinationofcough30breaths/minute
andcrackleshas a+LR of4.95 andLRof0.36[OcbinaP,2006].
Among165childrenaged6-59months,ahistoryofpreviousrespiratorydistress
and persistence of tachypnea after bronchodilator challenge
testhasa+LRof1.84andaLRof0.6 [CastroAV,2005].
Among 510 patients aged 2-59 months of age with cough and with
anyoneofthefollowing[Mahabee-GittensEM,2005]:
RRgreaterthan60perminuteacrossallageshas+LRof2.6(CI95%1.6-4.3),and-LRof0.77
Age>12monthshas+LRof1.5(CI95%1.2-1.9),andLRof0.59
Nasalflaring(amongpatientsaged>12months)+LRof5.2(CI95%2.2-12.2),andLRof0.71
CombinationofRR50/min,O2Sat96%andnasalflaringhas+LRof11.0(CI95%2.4-49.8)
Among570patientsaged1-16yearsofage,tachypneahas+LRof2.6and -LR
of 0.90; and combination of fever, decreased breath
sounds,cracklesandtachypneahas+LRof1.04andLRof0.20[LynchT,2004].
Among76patientsfrombirthto6moofage[deFatimaM,2005],
RRgreaterthan50withbacterialetiologyhasa+LRof1.2anda-LRof0.63;
andwithaviraletiology+LRof1.2and-LRof0.37
Chestindrawingwithbacterialetiologyhasa+LR2.3anda-LRof0.70;andwithviraletiology+LRof1.7and-LRof0.67
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*Likelihoodratio[LR]ofaround1indicatethatnousefulinformationforrulingthediagnosisinorouthasbeenproduced
from theclinical findings.ALR that is furtheraway from1 increases
reliability.Ahighlikelihoodratio(e.g.LR>10)indicatethatthesignorsymptom[oranydiagnostictest]canbeusedtoruleinthedisease,whilealowlikelihoodratios(e.g.LR
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CQ2.Whowillrequireadmission?
2004ClinicalPracticeGuidelineRecommendation
1.Apatientwhoisatmoderatetohighrisktodeveloppneumonia-relatedmortalityshouldbeadmitted[GradeD].
2.Apatientatminimaltolowriskcanbemanagedonanoutpatientbasis[GradeD].
UPDATEHIGHLIGHTS
1.Singleevidencesupportsthecurrentrecommendationonriskclassificationscheme.
2.Asingleclinicalindexthatsuggeststheneedforadmissionbecauseofpossiblehypoxemiaischestindrawing.
3. Indicesthatpredictmortalityincludeyoungage,malnutrition,
lackofHib/measlesvaccination,andhighoxygenrequirementonadmission.
Annotation2A.Riskclassificationscheme
Among221patientswithanimpressionofpCAP,noneofthe61and80patientsclassifiedaspCAPAandBrespectivelywereadmittedwithin48hours.Similarly,noneof
the 84 patients admitted as pCAP C were discharged or admitted to
ICU within 48hours after admission [Pocsidio C, 2007].SeeAppendixC
for the table showing the riskclassification.
Annotation2B.Individualindicespredictingtheneedforadmission
1.PhysicalexaminationofthechestinpredictinghypoxemiaAmong150patientsaged2-60months,chestindrawinghasa+LRof5.7and-LRof0.39inpredictingthepresenceandabsencerespectivelyofhypoxemia[BasnetS,2006].
2.AgeandnutritioninpredictingmortalityAmong30mortalitiesbecauseofpneumonia,youngage[2-5months]andweightforagez-scorelessthan-2SDhaveanORof2.20(95%CI1.06-4.54)and1.86(95%CI0.89-3.87),respectively[LupisanSP,2007].
3.Hib/measlesvaccinationonadmissioninpredictingmortalityAmong102mortalitiesbecauseofpneumonia,theabsenceofmeasles/HIbvaccinationhasanORof15.89(95%CI3.473-72.784),and8.31(95%CI3.5-19.3),respectively[Sadang-SaguinsinS,2006].
Annotation2C.DaycaremanagementofpCAPCAmong251patientsaged2-59monthswithsevereandveryseverepneumoniawithoutanyassociatedco-morbidities,successfulmanagementwaspossibleinadaycaresettingamong93.2%(95%CI,89-96)ofpatients[AshrafH,2007].
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CQ3.WhatdiagnosticaidsareinitiallyrequestedforapatientclassifiedaseitherPCAPAorPCAPBbeingmanagedinanambulatorysetting?
2004ClinicalPracticeGuidelineRecommendation
NodiagnosticaidsareinitiallyrequestedforapatientclassifiedaseitherPCAPAor
PCAPBwhoisbeingmanagedinanambulatorysetting[GradeD].
UPDATEHIGHLIGHT
The low risk of bacteremia does not warrant blood culture
determination innonseverepneumonia.
Annotation3A.Indicationforradiographicandlaboratorytests
TheTaskForceonpCAPhasnotencounteredstudiesinvestigatingthevalueofWBC,differentialcount,CRPandESRinthediagnosisofpCAPpatientsbeingmanagedonanoutpatientbasis.
Annotation3B.Bloodculture
In 540 patients aged 2-24 months, the risk of bacteremia among
patients seen asoutpatient is 1.6%. (95% CI 0.7-2.9).
Streptococcocus pneumoniae was the
causativeorganisminallcases[ShahS2003].
Annotation3C.Predictorforbacterialpathogen
Serumprocalcitoninhasbeenused todifferentiatebetweenviral,
atypicalandbacterialpathogenin100patientsagedlessthan2yearstomorethan5years[74outpatientsand26
inpatients]. A cut-off limit of > 2.0 ng/ml has a +LR of 1.69
and -LR of 0.73
forStreptococcuspneumoniae,anda+LRof2.31andLRof0.54forMycoplasmaspandChlamydiasp,respectively[DonM2007].Thistestisnotcurrentlyavailablelocally.
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CQ4.WhatdiagnosticaidsareinitiallyrequestedforapatientclassifiedaseitherPCAPCorPCAPDbeingmanagedinahospitalsetting?
2004ClinicalPracticeGuidelineRecommendation
1.Thefollowingshouldberoutinelyrequested:
a.Chestx-rayPA-lateral[GradeB]b.Whitebloodcellcount[GradeC]c.CultureandsensitivityofBloodforPCAPD[GradeD]Pleuralfluid[GradeD]Trachealaspirateuponinitialintubation[GradeD]Bloodgasand/orpulseoximetry[GradeD]
2.Thefollowingmayberequested:Cultureandsensitivityofsputumforolderchildren[GradeD]
3.Thefollowingshouldnotberoutinelyrequested:a.Erythrocytesedimentationrate[GradeA]b.C-reactiveprotein[GradeA]
UPDATEHIGHLIGHTS
1.
Chestradiographicevaluationisprimarilyutilizedasanintegralpartofaclinicalpredictionruleinidentifyingthepresenceofabacterialpathogen.Asanindividual
tool, it canbeused to assess severity andpresenceof
complications,andtopredictsubsequentcourseofillness.
2.
WBCandCRPhavealimitedvalueasanindividualtestindifferentiatingbacterial
from viral pneumonia. A CRP level [ 12 mg/dl] is associated
withnecrotizingpneumoniaand/orempyema.
3.
Singleevidencesuggestsa63mm/hvalueforESRinpredictingthepresenceofabacterialpathogen.
4. Themicrobiologicyieldforbloodculturerangedfrom1.2%to6.2%.
5.Highoxygenrequirementonadmissionisoneofthevariablesassociatedwithmortality.
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Annotation4A.Chestx-ray
Radiographicexaminationoffersthefollowinginformation.
1.Chestx-rayhasbeenusedasatooltopredictthetypeofpathogen
Chestx-rayisanintegralpartoftheclinicalpredictionrule[see
Clinical Question 5 and Appendix D] in initiating
antibiotictherapy[MorenoL,2006].However,itsvalueasanindividualtoolindifferentiating
bacterial from other types of infection isinsignificant as shown in
one report [Michelow IC, 2004]. In thisstudy of 154 patients aged 2
months17 years, the presence oflobar or segmental consolidation
with or without effusion can beseen among different pathogens such
as bacterial, viral
andatypicalorganisms(pvalue=0.06).Acompoundingvariableisthepresenceofmixedcausativeagentsinabouta
thirdofcasesofpneumonia inwhich the
radiographicpatternhasbeenshowntobesimilartothatseeninsinglepathogen[Tsolia
MN, 2004; Taina Juve n, 2004; Michelow IC, 2003; Don M,
2005;TajimaT,2006;LehtinenP,2006;HuangHH,2006;ChiangWC,2007].
2. Chest x ray has been used as an individual tool to assess
severity ofpneumonia
Presenceofnecrotizingpneumoniaand/orempyemaAmong 131 patients
aged 12 months of age, left-sidedpneumonia was significantly
associated with prolongedfever (p=0.02) and hospitalization
(p=0.043), and thepresenceofpleuraleffusion(OR2.65;95%CI1.096.47;p
value=0.031) compared with right-sided
pneumonia[GrafakouO,2004].
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b.PredictorofmortalityAmong102mortalitiesbecauseofpneumonia,multilobar(2lobes)
involvementhasanORof2.55(95%CI1.56.-5.64)ofmortality[Sadang-SaguinsinS,2006].In
30 mortalities because of pneumonia, the presence ofdense
infiltrates has an OR of 3.89 (95% CI
1.75-8.67)[LupisanSP,2007].
c.PredictoroftreatmentfailureAmong20%of218patients,bilateralconsolidationhasanORof3.10ofhavingtreatmentfailureonthe72ndhourofadmission[VictorR,2007].
Annotation4B.WBC
Evidence is weak in using white blood count as an individual
tool to predict bacterialpathogen
a. Among132patients5yold,the+LRand-LRforWBC>13,000 x 109/L
are 1.29 and 0.73, and WBC>17,000 x 109/L
are1.89and0.80,respectively[KorppiM,2004].
b.
Among862patientswithprovenRSVinfectionaged62398days,WBC>15,000x109/L,
theprobabilityofaconcurrent
seriousbacterialinfectionis4.7%[PurcellK,2007].
c. Among154patientsaged2months17years,nostatisticalsignificance
exists among WBCs of bacterial, viral, atypical
organismsandmixedinfection(pvalue=0.76)[MichelowIC,2004].
Annotation4C.Acutephasereactants
1.Creactiveprotein[CRP]
EvidenceisinconclusiveinusingCRPtopredictthepresenceofbacterialpathogen
a.
Among132patientsaged5yearsold,CRP>146mg/dlhasa+LRof1.75and-LRof0.43.[KorppiM,2004].
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b. Amongpairedserumsamplesfrom265patients,CRP from 6 to 250 mg/L
using latex agglutination test
hassensitivityof100%andspecificityof87%[RequejoH,2003].
Inonestudy,aCRPlevel12mg/dlhasanORof3.51(95%CI1.71-7.66) to
predict the presence of necrotizing pneumonia and/or
empyema[LinK,2006].
2.Erythrocytesedimentationrate[ESR]
Inonestudy,thereisevidencethatESRcanbeusedtopredictthepresenceofabacterialpathogen.Among132patientsaged5yold,ESRatavalueof63mm/hhasa+LRof3.50and-LR0.84[KorppiM,2004].
3.SerumprocalcitoninIntwostudies,thereisevidencethatserumprocalcitoninmaypredictthepresence
of a bacterial pathogen. This test however is not
currentlyavailablelocally
a. Among132patientsaged5yold,aprocalcitonin
levelof>0.84ng/Lhas a+LRof2.05 anda
-LR0.76[KorppiM,2004].b.Among57patientslessthan15yearsoldwithStreptococcuspneumoniae,procalcitonin>1ng/Lfoundinonly14patientshad+LRof2.40[KorppiM,2003].
Annotation4D.Microbiology
1. There are no studies dealing with determining the impact of
having to
obtainmicrobiologicexaminationontheoveralloutcomeofpCAP.
2.Twostudieshaveshowntheyieldforbloodcultureasfollows:
a.1.2%among157patients[TajimaT,2006].
b.6.2%among75patients[M.N.Tsolia,2004].
3.ImmunologicalassayandPCR
a. Among 550 paired samples for Streptococcus pneumoniae
andHaemophilusinfluenzaetypebpolysaccharideantigen,CIE,LAandDot-ELISA
using serum samples had a sensitivity of 91.1% to 100%, and
aspecificityof56.4%to100%[RequejoHI,2007].
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b.Among107patients,latexparticleagglutinationtest[LPAT]performedin
urine samples to detect Streptococcus pneumoniae and
Haemophilusinfluenzae type b polysaccharide antigen, has a +LR of
7.7 and -LR of0.25[NunesA,2004].
c. Among 389 patients, the sensitivity and specificity using
pathogen-specificmolecularbeaconprobeswereas
follows:96.2%and93.2%forStreptococcuspneumoniae,95.8%and95.4%forHemophilusinfluenzae,100%
and 100% for Streptococcus pyogenes, and 100% and 95.4%
forMycoplasmapneumoniae,respectively[MorozumiM,2006].
Annotation4E.Oxygensaturationand/orbloodgas
Inadditiontotheuseofdeterminingoxygensaturationand/orbloodgastotitrateFi02inmaintainingadequateoxygenation,itcanalsobeutilizedtopredictmortality.Among102childrenaged3monthsto19years,ahighoxygenrequirementonadmissionhasanORof8.31(95%CI3.5-19.3)atriskformortality[Sadang-SaguinsinS,2006].
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CQ5.Whenisantibioticrecommended?
2004ClinicalPracticeGuidelineRecommendation
Anantibioticisrecommended
1.forapatientclassifiedaseitherPCAPAorBandis
a.beyond2yearsofage[GradeB];or
b.havinghighgradefeverwithoutwheeze[GradeD]
2.forapatientclassifiedasPCAPCandis
a.beyond2yearsofage[GradeB];or
b.havinghighgradefeverwithoutwheeze[GradeD];or
c.havingalveolarconsolidationinthechestx-ray[GradeB];or
d.havingwhitebloodcellcount>15,000[GradeC]
3.forapatientclassifiedasPCAPD[GradeD]
UPDATEHIGHLIGHTS
1.Epidemiology
a.
Recentepidemiologictrendshowsthatmorethan50%ofhospitalizedcasesofpCAPwillrequireantibiotic.
b.
Theimportanceofmixedinfectionascausativeagentsshouldbeclarifiedasitisresponsibleforaboutone-thirdofallidentifiedcausesofhospitalizedpCAP.
2.Microbiologictests
TheyieldindetectingbacteremiainpCAPremainstobelowat1.2%to26%.
3.Predictorsofbacterialpathogen.
a.
Aclinicalpredictionrulethatmakesuseofabacterialpneumoniascore[BPS]of>4canpredictthepresenceofabacterialpathogeninhospitalizedpatientsagedonemonthtofiveyears.
b.Otherindividualparametersincludethefollowing. Increasing age
generally correlates with the presence of
antibiotic-requiring pathogen. Identifying a specific age as
towhenanantibioticshouldbestartedisdifficult.
ThereissingleevidenceintheuseofESRwithavalueof63mm/hinpredictingthepresenceofabacterialpathogen.
Thereisweakevidenceintheuseofclinicalsymptomatology,chestx-ray,WBCandCRPaspredictorsofbacterialpathogen.
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Annotation5A.Establishingtheetiology
A.Microbiology
There are five [5] studies that have looked simultaneously into
viral, bacterial,atypicalorganismsand mixed infection [Michelow I,
2004,; Don M, 2005; Tsolia MN,2005; Tajima T, 2006; Chang WC,
2007]. Etiology was determined through
differentmethodologiesusingculture,serology,andpneumolysin-basedpolymerasechainreaction
assays. It is important to note that all patients in these studies
arehospitalized[except
inonestudydealingwithbothambulatoryandhospitalizedpatients], and
are from developed economies where the rate of vaccination
ishigherthaninthethirdworld.Asthetablebelowindicates,organismsrequiringantibioticcoverageaccountsformorethan50%acrossallages.Theimportanceof
mixed infection needs to be further studied as there is an
observationalevidenceofahighmorbidityfrom2%to35%.
AuthorYear
Age[Years]
SubjectsN
KnownEtiologyN[%]
Virusa%
Bacteriaa%
AtypicalPathogena%
MixedInfection%
Chiang2007
0.1-16
1702
646[37.9%]
5.5%
10.3%
20.3%
2.0%
Tajima2006
0.1-13
157
126[80.2%]
44.0%
80.1%
25.3%
18.0%b
Don2005
0.3-16
101
66[65.3%]
42.0%
30.3%
53.0%
30.0%
Tsolia2005
5-14
75
58[77.3%]
65.0%
7.0%
48.2%
35.0%
Michelow2004
0.2-17
154
122[79.2%]
45.0%
60.0%
33.6%
23.0%
MEAN
23.6%
26.5%
26.0%
10.7%TOTAL
2189 1018[46.5%]
aAllcasesincludingmixedinfectionb28(17.8%)hadviralbacterialinfection.1(0.6%)hadMycoplasmal-bacterialpneumonia
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20
B.Establishingtheetiology
TheTaskForceonpCAPrecognizestheimportanceofestablishingthepresenceofabacterialpathogenthroughculturestudies.However,therearelimitationstothisapproachsuchasinvasivenessoftheprocedureasinlungpuncture,lowyield(1.2%to26%inbloodculture)[MichelowI,2004;TsoliaMN,2005;TajimaT,2006],andtheavailabilityofresultsatalatertime.Thereareteststhatcanbeusedtorapidlydetectbacterialpathogensbutwhichareeithernotreadilyavailablelocallyorexpensive.Theseareimmunologicalassays(CIE,
LA and Dot-ELISA in detecting Streptococcus pneumoniae
andHaemophilus influenza b antigen with sensitivity of 91.1% to
100%
andspecificityof49.5%to100%in550pairedserum,pleuralfluidandurinesamples)[Requejo
HI, 2007]; PCR (pathogen-specific molecular beacon probes) with
thefollowing sensitivity and specificity in 389 patients: 96.2% and
93.2%
forStreptococcuspneumoniae,95.8%and95.4%forHaemophilusinfluenzae,100%and
100% for Streptococcus pyogenes, and 100% and 95.4% for
Mycoplasmapneumoniae[MorozumiM,2006];andlatexparticleagglutinationtest[sensitivityof77.3%(95%CI,61.8-to88.0)andspecificityof90.3%(95%CI,79.5-96.0)indetecting
Streptococcus pneumoniae and Haemophilus influenzae type
bpolysaccharideantigeninurinesamplesof107patients[NunesA,2004].
Annotation5B.Surrogatepredictorsofbacterialetiology
A.Clinicalpredictionrule
A clinical prediction rule among hospitalized children aged one
month to fiveyearshasbeendeveloped todetermine
thepresenceofabacterialpathogen.Anaggregatebacterialpneumoniascore[BPS]of>4hasasensitivityandspecificityof
100% (95% CI 84.6100) and 93.9% (95% CI 87.897.5) respectively.
Thecomputed+LRandLRare>10and
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21
B.Individualclinicalpredictors
1.Age
a.Asummaryoffour[4]epidemiologicreportsonalltypesoforganismsthatstratifiestheoccurrenceofetiologicagentsastoageisshownbelow.Extracted
data are heterogenous making it difficult to come up with astrong
conclusion as to what age should antibiotic be likely
started.[Michelow I, 2004 ;Don M,2005; Tajima T2006;ChangWC 200].
In
twostudies,increasingagecorrelateswithahigherchanceofthepresenceofbacterialagents.
In all four studies, there is a trend in increasing frequency
ofatypicalorganism.
AuthorYear
Age[Years]
Subjects[N]
KnownEtiology[N]
Virusa[%]
Bacteriaa[%]
AtypicalPathogena[%]
MixedInfection[%]
Chiang2007
0.1-165
1702 653 5.56.66.90.9
10.35.213.28.5
20.35.016.531.0
2.0
Tajima2006
0.1-135
157
126 40.052.747.30
43.069.632.84.2
18.03.542.864.2
19.0;[2.0b]83.017.00
Don2005
0.3-165
101 66 18.8a31.657.810.5
17.522.238.838.8
34.65.722.871.4
29.736.822.734.2
Michelow2004
0.2-175
154 122
19.055.0c48.0c38.0c
26.055.0c68.0c55.0c
11.0
47.0d53.0
23.0
aSingleandmixedinfectionbBacterialandMycoplasmaspcInterpolateddatadPercentagedataapplicabletochildrenbelow5years
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22
b. There are five [5] pathogen-directed, across-all-ages studies
dealing
withatypicalorganisms[OthmanN,2005;GarciaMC,2002-2005;TsaiMH,2005;ButunY,2006;BambaM,2006].Twostudies,oneofwhichwasdoneinthelocalsetting,were
from developing economies. As shown below, more than half of the
totalnumberofcaseswithatypicalorganismarechildrenbelow5yearsofageinthreeofthefivestudies.
AuthorYear
Age[Years]
NAgewith+antibodytiterforMycoplasmaspand/orChlamydiasp[Years]
Prevalence[%]
Butun2006
0.3-12 100
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23
2.Whitebloodcellcount[WBC]
a.Among132patients5yearsold,WBCcut-offlevelsof>13,000x109/L,and>17,000x109/Lhave+LRof1.29and-LRof0.73,and+LRof1.89and-LRof0.80,respectively[Korppi,2004].
b. Among 862 patients with proven RSV infection aged 6 days8
yearsand a WBC cut-off level of > 15,000 x 109/L, the
probability of
aconcurrentseriousbacterialinfectionis4.7%[PurcellK,2007].
c.Among154patientsaged2months17years,nostatisticaldifferenceexists
as to the WBC levels among bacterial, viral, atypical and
mixedinfection(pvalue=0.76)[MichelowIC,2004].
3.C-reactiveprotein[CRP]
a.Among132patientsaged5yearsold,aCRPvalueof>146mg/dlhasa+LRof1.75anda-LRof0.43[Korppi,2004].
b.Amongpairedserumsamplesfrom265patients,qualitativedeterminationofCRPhasasensitivityof100%andspecificityof87.3%in
detecting Streptococcus pneumoniae, Haemophilus influenzae
b,StaphylococcusaureusandNeisseriameningitidis[RequejoH,2003].
4. Chestx-raystudies
a.Among54patientsaged2monthsto17years,nostatisticaldifferenceexists
as to the presence of lobar or segmental consolidation with
orwithout effusion among bacterial, viral, atypical organisms and
mixedinfection(pvalue=.06)[MichelowIC,2004].
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24
CQ6.Whatempirictreatmentshouldbeadministeredifabacterialetiologyisstronglyconsidered?
2004ClinicalPracticeGuidelineRecommendation
1.ForapatientclassifiedasPCAPAorBwithoutpreviousantibiotic,oralamoxicillin[40-50mg/kg/dayin3divideddoses]isthedrugofchoice[GradeD].
2.ForapatientclassifiedasPCAPCwithoutpreviousantibioticandwhohascompletedtheprimaryimmunizationagainstHaemophilusinfluenzatypeb,penicillinG[100,000units/kg/dayin4divideddoses]isthedrugofchoice[GradeD].IfaprimaryimmunizationagainstHibhasnotbeencompleted,intravenousampicillin[100mg/kg/dayin4divideddoses]shouldbegiven[GradeD].
3.ForapatientclassifiedasPCAPD,aspecialistshouldbeconsulted[GradeD].
UPDATEHIGHLIGHTS
1Epidemiology
a.EpidemiologictrendindevelopedeconomiessuggeststhatStreptococcuspneumoniaeandMycoplasmapneumoniaeappearto
be the most common pathogens causing
community-acquiredpneumoniaacrossallages.
b.
Animportantemergingpathogeniscommunity-acquiredmethicillinresistantStaphylococcusaureus[CA-MRSA].
2.Antibioticresistance
Dataon2006AntimicrobialResistanceSurveillanceProgramshowedresistance
rate of less than 10% for penicillin and chloramphenicol
withStreptococcuspneumoniaeinfection,andforampicillinwithHaemophilusinfluenzae.
3.Empiricantibiotictherapy
a.ForpCAPAandB[nonseverepneumonia],thereisevidencefortheuseof
amoxicillin [45 mg/kg/day in three divided doses for a
minimumduration of three days]. For those with known
hypersensitivity
toamoxicillin,amacrolidemaybeconsidered.Theuseofcotrimoxazoleisdiscouragedbecauseofhighfailureandresistancerates.
b.ForpCAPC[severepneumonia],equalefficacieswerenotedbetweenoralamoxicillinandparenteralpenicillinamongpatientswhocantoleratefeeding;
and between monotherapy and combination therapy for thosewho cannot
tolerate feeding. Among monotherapy available for
use,parenteralampicillinisthebestchoiceconsideringitscost.
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25
Annotation6A.CausesofpCAPrequiringantibioticcoverage
A.PredominantpathogenAmongpatientswithknownetiology,StreptococcuspneumoniaeandatypicalorganismsgenerallyaccountformajorityofcausesofpCAPacrossallages[ChangWC,2007;HuangHH,2006;TajimaT,2006;DonM,2005;TsoliaMN,2005;MichelowI,2004]
aStreptococcuspneumoniaeismorecommonabove5yearsofage[Chiang,2007;Michelow2004].
B.Emergingpathogen:Community-acquiredmethicillin-resistantStaphylococcusaureus[CA-MRSA]
The epidemiology of community-acquired methicillin-resistant
Staphylococcusaureus [CA-MRSA] has been recently reviewed. In one
study conducted
inDriscollChildrensHospital,CorpusChristiTexasUSA,93%ofatotalof1002MRSA
were identified from 1990 through 2003 as CA-MRSA. Cases rangedfrom
none to nine per year from 1990 through 1999 and then
increasedexponentiallyfrom36in2000to459in2003[PurcellK.2005;PaintsilE,2007].Inthelocal
setting, the Antimicrobial Resistance Surveillance Program reported
ahospitalrateofMRSAof31%in2005andin2006[CarlosCC,2005;CarlosCC,2006].
AuthorYear
Age[Years]
Streptococcuspneumoniaea[%]
Haemophilusinfluenazae[%]
Mycoplasmasp[%]
Chlamydiasp[%]
Chiang2007
0.1-16
17.4% 0.4% 28.6% 0%
Tajima2006
0.1-13
35.7%
26.1% 17.4% 0%
Huang2006
2.0-14
8.9%
1.2%
7.1%
1.8%
Don2005
0.3-16
17.8%
4.5%
26.7%
7.9%
Tsolia2005
5.0-14 7.0% 0% 35.0% 3.0%
Michelow2004
0.2-17
73.0% 0% 14.0% 9.0%
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26
Annotation6B.Antibioticresistance
A.Antibioticresistancesurveillancereports
1.Localdata:AntimicrobialResistanceSurveillanceProgram
Of24112,23749,29782and25768 isolates
for2003,2004,2005and2006respectively as reported by the Research
Institute of Tropical Medicine, theresistance rates of hospital
infection involving Streptococcus pneumoniae andHemophilus
influenzae to different antibiotics are shown below [Carlos
CC,2003;CarlosCC,2004;CarlosCC,2005;CarlosCC,2006]:
aScreeningwith1ugoxacillindisc
2.Asiandata:AsianNetworkforSurveillanceofResistantPathogens
Of 555 isolates of Streptococcus pneumoniae from ten Asian
countries
(Korea,China,HongKong,Thailand,Taiwan,India,SriLanka,Singapore,MalaysiaandVietnam)
as reported by the Asian Network for Surveillance of
ResistantPathogens(ANSORP),329(59.3%)wereresistanttoerythromycin
[Jae-HoonSong,2004].
3.Individualcountrydata:Japan
Among2,462clinicalspecimenscollectedbetweenApril2002andMarch2004from
pediatric outpatients with respiratory tract infections, about 10
macrolide-resistant Mycoplasma pneumoniae (MICs of >1ug/m) out
of a total of
195isolatedstrainshavebeenreported.Resistancerateinthisstudyis1.9%[MorozumiM,2005].
.
Penicillina
Chloramphenicol
Cotrimoxazole
Ampicillin
2003
04
05
06
2003
04
05
06
2003
04
05
06
2003
04
05
06
StreptococcusPneumoniae
9%
5%
11%
6%
3%
5%
4%
5%
9%
15%
16%
14%
Nodata
Nodata
Nodata
Nodata
HaemophilusInfluenzae
Nodata
Nodata
Nodata
Nodata
13%
10%
20%
14%
18%
36%
15%
16%
13%
10%
10%
9%
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27
Annotation6C.AntibioticregimenforPCAPAorB[nonseverepneumonia]
A.OralAmoxicillin
1. Comparativetrial
a.
InaCochranesystematicreviewusingfailurerateasanoutcomemeasure, the
rate was higher in cotrimoxazole compared to
amoxicillin(OR1.33;95%CI1.05-1.67)[KabraSK;2006].
b.
InaCochranesystematicreviewusingfailurerateasanoutcomemeasure,theratewaslowerintheamoxicillingroupcomparedtochloramphenicol(OR0.64;95%CI0.41-1.00)[KabraSK;2006].
c.
Therearetwo[2]studiescomparingamoxicillinwitheitherazithromycinorerythromycin.
Amoxicillin versus azithromycin using end-of-treatment
chestx-rayandclinicalparametersasoutcomemeasures
Among47patientsaged1month-14years,usingchestx-ray on day 7 as
outcome measure showed improvementgreater than 75% compared with
baseline in
theazithromycingroupversusthosewhoreceivedamoxicillin[81.0% vs.
60.9%, p value = 0.09]. No difference existsbetweenthetwogroups
inotherparameterssuchasfever,cracklesanduseofaccessorymusclesonday7and14oftreatment[KoganR;2003].
Amoxicillin versus erythromycin using cure rate as
outcomemeasure
Among85patients aged4months-19 years,
therewasnodifferencebetweenamoxicillinanderythromycinastocurerate(pvalue=0.274)[RomuloAC,2006].
d.Forthosewithknownhypersensivitytoamoxicillin,amacrolideantibioticcanbeconsidered.
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28
2. Treatmentregimen
a.
Standarddoseversusdoubledoseusingtreatmentfailureasoutcomemeasure
Among 876 patients aged 2-59 months, the standard dose
ofamoxicillin at 45 mg/kg/day did not show any
statisticallysignificantdifferencecomparedwithdoubledoseamoxicillinat90mg/kg/dayusingtreatmentfailurebyday5(4.5%inthestandardand
5.7% in the double dose, p value = 0.55), and
cumulativetreatmentfailureincludingrelapses(5.9%inthestandardand7.9%inthedoubledose,pvalue=0.29)asoutcomemeasures[HazirT,2007].
b.
TIDdosingfrequencyversusBIDusingpharmacokineticstudiesasoutcomemeasure
Among266patients aged3-59months inwhomamoxicillinwasgivenorally
either
at25mg/kg/doseBIDor15mg/kg/doseTID,allbuttwochildrenhadplasmaamoxicillinconcentrationsabove0.5ug/mlfor>50%ofthedoseinterval[FonsecaW,2003].Thereareno
studies comparing the clinical outcome of patients
withpneumoniaonTIDregimenversusBID.
c.
Three-dayversusfive-daydurationusingclinicalcurerateandrelapserateasoutcomemeasures
Among 2188 patients aged 2-59 months, clinical cure rates
withthree days and five days treatment were 89.5% and
89.9%,respectively
(absolutedifference0.4,95%CI2.1-3.0).Therewasnodifference in
relapse ratebetween the
twogroupsafter5days(RR=1.22;absolutedifference1.0,95%CI1-3).Limitationssuchas
the study was performed in patients with clinical suspicion
ofpneumonia without radiographic evidence and
insufficientdetailingofpatientshistorywerenoted[Agarwal,2004].
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29
B.Otherantibioticoptions
1.Cotrimoxazole
a.ComparativetrialusingcurerateasoutcomemeasureThereisoneCochranesystematicreviewdealingwithantibiotictreatmentof
pCAP showing procaine penicillin having better cure rate
comparedwithco-trimoxazole(OR2.64;95%CI1.57-4.45)[KabraSK;2006].
b.TreatmentregimenusingtreatmentfailurerateasanoutcomemeasureAmong
1134 patients aged 2-59 months, treatment failure occurred in112
(19.4%) on standard dose [4 mg trimethoprim plus 20
mgsulfamethoxazole/kg of body weight] group and in 118 (21.2%)
ondouble-dose(RR1.10;95%CI0.871.37)[ZebaA,2005].
2.Azithromycin,erythromycinandco-amoxyclavulanicacidusingcurerateasanoutcomemeasure
In a Cochrane systematic review dealing with antibiotic
treatment
ofpCAP,therewasnodifferencebetweenazithromycinanderythromycin(OR1.17;95%CI0.70-1.95);orazithromycinandco-amoxyclavulanicacid(OR1.02;95%CI0.54-1.95)[KabraSK;2006].
3.ClarithromycinextendedreleaseusingcurerateasanoutcomemeasureAmong21patientsaged6to16years,thereisnodifferenceastocureratebetween
extended release clarithromycin once a day and the
standardclarithromycintwiceaday(90%vs90.1%)[BlockSL,2006].
4.Antibioticsforcommunityacquiredlowerrespiratorytractinfections(LRTI)secondarytoMycoplasmapneumoniae[GavranichJB,2005].
A Cochrane systematic review dealing with antibiotics for
communityacquired lower respiratory tract infections (LRTI) failed
to find anyrandomisedcontrolledtrialwhichspecificallylookedat
theeffectivenessofantibiotics forLRTIsecondary toM.pneumoniae. In
the subgroupofchildren with LRTI secondary toM. pneumoniae the
intervention was amacrolide antibiotic versus a non-macrolide
antibiotic,
usuallyamoxicillin-clavulanate.Thissubgroupidentifiedonly38childrenwithM.pneumoniae
infection and there were insufficient data to analyse
theefficacyofmacrolideantibioticsinthisgroup.
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30
ANNOTATION6D.PCAPCorseverepneumonia
A.Monotherapy
Parenteralpenicillinvsoralamoxicillin
ACochranesystematicreviewusingfailurerateasanoutcomemeasure
showed no difference between injectable penicillin and
oralamoxicillin(OR1.03;95%CI0.81to1.31)[KabraSK;2006].Includedinthis
review is a study among 1702 patients aged 3-59 months
whoreceivedeitheroralamoxicillinorparenteralpenicillin.Resultsshowedthat
treatment failurewas19%ineithergroup
(riskdifference0.4%,95%CI-4.2-3.3)[Addo-Yobo,2004].
Among246patientsaged6monthsto16yearswithradiologicallyconfirmedpneumonia,nosignificantdifferenceexistsbetweenthegroupon
oral amoxicillin versus IV benzylpenicillin using time
fortemperaturetosettle
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31
3.
Parenteralpenicillinpluschloramphenicolversuscefuroximeusingclinicalparametersasoutcomemeasures
Usingclinicalparametersasoutcomemeasuresamong88patientsaged2
months-18 years, early defervescence (p value=0.006), absence
oftachypnea (pvalue=0.024),absenceof chest retractions
(pvalue=0.001),and shorter hospital stay (p value=0.029) were noted
among patientstreated with penicillin G/Chloramphenicol compared
with cefuroxime[CarlosGP,2006].
4.
Parenteralpenicillinplusgentamicinversuschloramphenicolusingre-hospitalizationrate,deathratesandadverseeventsasoutcomemeasures
In a Cochrane systematic review using re-hospitalization rate
before
30daysasoutcomemeasure,theuseofparenteralpenicillinplusgentamycinwasbetter
than chloramphenicol alone (OR1.61;95%CI1.02
to2.55).Deathratesandadverseeventsweresimilarinbothgroups[KabraSK;2006].
5.
Parenteralpenicillinplusgentamicinversusamoxicillin/clavulanateusingclinicalparametersasoutcomemeasures
Usingclinicalparametersasoutcomemeasuresamong71patientsaged2-59
months, the mean time taken for normalization of tachypnea,hypoxia,
chest wall indrawing and inability to feed was similar for
bothgroupsreceivingpenicillinplusgentamicinversusamoxicillin/clavulanate(pvalue>0.05)[BansalA,2006]
6.
Parenteralampicillinplusgentamicinversusparenteralampicillinaloneusingclinicalparametersasoutcomemeasures
Usingclinicalparametersasoutcomeparametersamong40patientsaged2
months to 5 years who received either combination therapy of
IVampicillin and gentamicin versus IV ampicillin alone, fever
clearancetime, improvement of respiratory rate, improvement of
chest
indrawingandresolutionofrhonchiwerecomparablebetweenthetwogroups(pvalue
-
32
7.Othertreatmentregimens
a. Amoxicillin/sulbactam versus cefuroxime using defervescence
asoutcomemeasure
Usingdefervesecenceasanoutcomemeasureamong62
patientsaged3months-15yearswhoreceivedeither
amoxicillin/sulbactamorcefuroxime,bothtreatmentarms
werecomparable(97%foramoxicillin/sulbactamvs100%
forcefuroxime)[LoveraD,2005].
b.Chloramphenicol
Among 250 children treated with chloramphenicol,
98%hadafavorabletreatmentoutcome[AyapJ,2006]
C.Community-acquiredMRSA
Forsuspectedcasesofcommunity-acquiredMRSA,immediatereferraltoanappropriatespecialist
isnecessary.ThefollowinginformationservestoprovidebasicknowledgeinthetherapeuticoptionsdealingwithMRSA[StrategiesforClinicalManagementofMRSAinthecommunity:SummaryofanExpertsmeeting,2006;ShelburneS,2004].
a.
Antibioticsusceptibilitybasedonculturestudiesshouldbefollowed.
b.
VancomycinremainstobethefirstlinetherapyforsevereinfectionspossiblycausedbyMRSA.
c.
Community-associatedMRSAweremorelikelytobesynergisticallyinhibitedby
combinations of vancomycin and gentamicin (p value =0.025)
versusvancomycinalone.
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33
CQ7.Whattreatmentshouldbeinitiallygivenifaviraletiologyisstronglyconsidered?
2004ClinicalPracticeGuidelineRecommendation
1.Ancillarytreatmentshouldonlybegiven[GradeD].
2.Oseltamivir[2mg/kg/doseBIDfor5days]oramantadine[4.4-8.8mg/kg/dayfor3-5days]maybegivenforinfluenzathatiseitherconfirmedbylaboratory[GradeB]oroccurringas
anoutbreak[GradeD].
UPDATEHIGHLIGHT
Oseltamivirremainstobethedrugofchoiceforlaboratoryconfirmedcasesofinfluenza.
Annotation7A.Definitetreatment
Influenza
In a Cochrane systematic review, oseltamivir reduced the median
duration ofillness by 26% (or 36 hours) in healthy children with
laboratory-confirmedinfluenza(pvalue
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34
CQ8.Whencanapatientbeconsideredasrespondingtothecurrentantibiotic?
2004ClinicalPracticeGuidelineRecommendation
1.
Decreaseinrespiratorysigns[particularlytachypnea]anddefervescencewithin72hoursafterinitiationofantibioticarepredictorsoffavorabletherapeuticresponse[GradeD].
2.
Persistenceofsymptomsbeyond72hoursafterinitiationofantibioticsrequiresre-evaluation[GradeB].
3.
Endoftreatmentchestx-ray[GradeB],WBC,ESRorCRPshouldnotbedonetoassesstherapeuticresponsetoantibiotic[GradeD].
UPDATEHIGHLIGHTS
1.Inchildrenwithnonseverepneumonia,clinicalindexsuggestiveofgoodtherapeutic
response is a respiratory rate >5 breaths/min slower than
baselinerecordingatthe72ndhour.
2.Inchildrenwithseverepneumonia,clinicalindicessuggestiveofgoodtherapeutic
response are defervescense, decrease in tachypnea and
chestindrawing,increaseinoxygensaturation,andabilitytofeedwithin48hours.
Annotation8A.Treatmentresponse
A.Background
The clinical outcome definition of improved provided by the
World HealthOrganizationin1990isarespiratoryrate
-
35
B.Responsetotreatment
1.Ambulatorypatients
RespiratoryrateAmong876patientsaged2-59monthswithnonseverepneumonia,clinical
improvement on the 72nd hour is respiratory rate
>5breaths/minslowerthanbaselinerecording[HazirT,2006].
2.Hospitalizedpatients
DurationoffeverAmong 153 children aged 1 month to 16 years, 91%
becameafebrilewithin48hours.Childrenwithbacteremicpneumococcalpneumonia
have become afebrile within an average of 22
hoursafteronsetofantimicrobialtherapy[JuvenT,2006].
RespiratoryrateAveragetimeofrecoveryfromtachypneaamong71childrenaged2-59monthsis38-40hours[BansalA,2006].
OxygensaturationAverage timeof recovery fromSpO2(
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36
CQ9.Whatshouldbedoneifapatientisnotrespondingtocurrentantibiotictherapy?
2004ClinicalPracticeGuidelineRecommendation
1.
IfanoutpatientclassifiedaseitherPCAPAorPCAPBisnotrespondingtothecurrentantibioticwithin72hours,consideranyoneofthefollowing[GradeD]:a.changetheinitialantibiotic;orb.startanoralmacrolide;orc.reevaluatediagnosis.
2.
IfaninpatientclassifiedasPCAPCisnotrespondingtothecurrentantibioticwithin72hours,considerconsultationwithaspecialistbecauseofthefollowingpossibilities[GradeD]:a.penicillinresistantStreptococcuspneumoniae;orb.presenceofcomplications[pulmonaryorextrapulmonary];or
c.otherdiagnosis
3.IfaninpatientclassifiedasPCAPDisnotrespondingtothecurrentantibioticwithin72hours,considerimmediatere-consultationwithaspecialist[GradeD].
UPDATEHIGHLIGHTS
1.Therearenostudiesdealingwiththerapeuticinterventionsfollowingtreatmentfailureamongchildrenhavingcommunity-acquiredpneumonia.
2.Adefinitionoftreatmentfailurefornonseverepneumoniaisasfollows:
a.Samestatus.Thisisdefinedasrespiratoryrate>age-specificrangebut+5breaths/mintothebaselinereadingandwithoutlowerchestindrawingoranydangersigns;
b.Worsestatus.Thisisdefinedasdevelopinglowerchestindrawingorwithanyofthedangersigns.
3.Thecausesoftreatmentfailureincludecoinfectionwithrespiratorysyncytialvirus
or mixed infection, non-adherence to treatment for nonsevere
pneumonia,resistancetoantibiotics,clinicalsepsis,andprogressivepneumonia.
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37
Annotation9A.Courseofactionintreatmentfailure
There are no comparative trials specifically dealing with
therapeutic
interventionsfollowingtreatmentfailureamongchildrenhavingcommunity-acquiredpneumonia.
Annotation9B.Definitionoftreatmentfailure
A.Background
The clinical outcome definitions of same and worse status
provided by
theWorldHealthOrganizationin1990areasfollows[WHO1990]:
Same:Respiratoryrate>age-specificrangewithoutlowerchestindrawingoranydangersigns(centralcyanosis,inabilitytodrink,abnormallysleepyorconvulsions)
Worse:Developedlowerchestindrawingoranyofthedangersigns(centralcyanosis,inabilitytodrink,abnormallysleepy,orconvulsions)
B.Treatmentfailure
1.pCAPAandB[Nonseverepneumonia]
Among876patientsaged2-59monthswithnonseverepneumonia,treatment
failure has been redefined on the 72nd hour after
initiatingantibioticaseither [a] samestatus : respiratory
rate>age-specific
rangebut+5breaths/mintothebaselinereadingwithoutlowerchestindrawingordangersigns(centralcyanosis,inabilitytodrink,abnormallysleepyorconvulsions),or[b]worsestatus:developedlowerchestindrawingoranyofthedangersigns(centralcyanosis,inabilitytodrink,abnormallysleepyorconvulsions)[HazirT,2006].
2.pCAPC[Severepneumonia]
Therearenostudiesinhospitalizedpatients.
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38
Annotation9C.Causesoffailureinthetreatmentofbacterialpneumonia
A.Causesoftreatmentfailureareasfollows:
1.pCAPAandB[nonseverepneumonia]
Among2188patientsaged2-59months,10.3%werereportedtobecasesof
treatment failure. Causes include an association with isolation
ofrespiratory syncytial virus (an adjusted OR 1.95; 95% CI
1.0-3.8),
andnon-adherencewithtreatment(OR11.57;95%CI7.4-18.0)[Agarwal,2004].
2.pCAPC[severepneumonia]
a.Among71patientsaged2-59months,2.8%werereportedtobecasesoftreatment
failure. Causes include resistance to antibiotics and
worseningclinicalcondition[BansalA,2006].
b.Among218patientsaged3monthsto19years,20%werereportedtobe cases
of treatment failure. Causes include clinical sepsis
andprogressivepneumonia[VictorR,2007].
c.Among60patientsaged3monthstofiveyears,23%wasreportedtobetreatment
failure. Progressive pneumonia has been cited as the
mostcommoncauseat57%.[PradaC,2007]
d.Among153patientsaged1monthto16years,9%wasreportedtobetreatmentfailure.Ofthese,50%hadevidenceofmixedinfection.[JuvenT,2004]
-
39
CQ10.Whencanswitchtherapyinbacterialpneumoniabestarted?
2004ClinicalPracticeGuidelineRecommendation
Switchfromintravenousantibioticadministrationtooralform2-3daysafterInitiationofantibioticisrecommendedinapatient[GradeD]who
[a]isrespondingtotheinitialantibiotictherapy,
[b]isabletofeedwithintactgastrointestinalabsorption;and
[c]doesnothaveanypulmonaryorextrapulmonarycomplications.
UPDATEHIGHLIGHTS
Switch therapy from three [3] days of IV ampicillin to four [4]
days of eitheramoxicillin or cotrimoxazole may be used among
patients admitted because
ofcommunity-acquiredpneumonia.Amoxicillinispreferredbecauseofhighfailureandresistanceratesreportedintheuseofcotrimoxazole.
Annotation10A.Comparativetrial
Usingclinicalcureuptoday14astheoutcomemeasureamong21patientsaged3monthsto5years,nosignificantstatisticaldifferenceexistsbetweenthatwith7daysofIVampicillinversus3daysIVampicillinplus4daysoralamoxicillin(pvalue>0.05)[Ochoa-RagazaS,2004].
Usingclinicalcureuptoday7astheoutcomemeasureamong26patientsaged3monthsto5yearson3daysofIVampicillin,nosignificantstatisticaldifferenceexists(pvalue
=0.6) between thatwith cotrimoxazoleversusoral amoxicillin as
stepdowntherapy (p value > 0.05) [Marquez W,2007]. The use of
cotrimoxazole however isdiscouragedbecauseofhigh failureand
resistance rates [CarlosCC,2003;Carlos
CC,2004;CarlosCC,2005;CarlosCC,200;6KabraSK;2006].
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40
CQ11.Whatancillarytreatmentcanbegiven?
2004ClinicalPracticeGuidelineRecommendation
1.Amonginpatients,oxygenandhydrationshouldbegivenifneeded[GradeD].
2.Coughpreparations,chestphysiotherapy,bronchialhygiene,nebulizationusingnormalsalinesolution,steaminhalation,topicalsolution,bronchodilatorsandherbalmedicinesarenotroutinelygivenincommunity-acquiredpneumonia[GradeD].
3.Inthepresenceofwheezing,abronchodilatormaybeadministered[GradeD].
UPDATEHIGHLIGHTS
1.
Thereisnoevidencetosupporttheuseofhydrationorfluidrestrictionandcoughpreparationinthemanagementofpneumonia.
2. ThevalueofelementalzincorvitaminAisinconclusive.
3.
Singlestudydemonstratedbenefitforeithervirgincoconutoilorprobioticasadjuncttherapyinpneumonia.
Annotation11A.Fluidmanagement
A.Increasefluidintake
In a Cochrane systematic review among ambulatory patients with
acuterespiratory infection, no randomized controlled trials
assessing the effect
ofincreasingfluidintakeinacuterespiratoryinfectionswerefound[GuppyMPB,2005].
B.Fluidrestriction
Therearenocontrolledstudiesassessingtheeffectofrestrictingfluidintakeamongpatientshospitalizedwithpneumonia.
In a Cochrane systematic review among hospitalized patients, the
rate
ofhyponatremiahasbeenreportedtobe31%-45%fornondehydratedchildrenwithmoderatetoseverepneumonia[GuppyMPB,2005].Among50childrenaged259monthswithsevere,andveryseverepneumonia,extracellularwater
[ECW]andplasmavolume[PV]weremoderately increased[ECW318 (45)vs308
(49)ml/kg,PV53.2 (2.3)vs52.1 (2.3)ml/kg,
p,0.05].TheSpO2showedasignificantlinearrelationshipwithECWandPV(0.46and0.42respectively,p=0.05)[SinghiS,2005].
-
41
Annotation11B.Coughpreparation
A.InaCochranesystematicreview,onestudyperformedexclusivelyinchildrenusing
three different mucolytics (bromhexine, ambroxol, neltenexine)
demonstrated
nosignificantdifferencefortheprimaryoutcomeofnotcuredornotimproved(OR0.40,95%CI0.10-1.62),andsecondaryoutcomeofnoimprovement(OR0.34,95%CI0.09to1.36)[ChangCC,2007].
B. Among ambulatory 62 children aged 3 month 19 years, there was
no statisticaldifference in improving cough using verbal category
Descriptive Scoring
Systembetweenthegrouponambroxolandthegroupwithouttreatment(pvalue>0.05)[AlquizaG,2006]
C. Among hospitalized 70 children aged 3 months 19 years, there
was no statisticaldifference indecreasing respiratory rateand
intercostal
retractionsbetweensalbutamol,normalsalinesolutionandnotreatment(p>0.05)[GotosL,2004].
Annotation11C.Micronutrients
A.InaCochranesystematicreview,fivetrialsinvolving1453patientsyoungerthan15
years old with non-measles pneumonia did not demonstrate
significant
differencebetweenthosetreatedwithadjunctivevitaminAandplaceboastomortality,measuresofmorbidity,noraneffectontheclinicalcourseofpneumonia(pooledoddsratioOR1.49;95%CI0.66to3.35)[NiJ,2005].
B. In a systematic review of five double-blinded, randomized,
controlled interventionstudies
involving2177childrenaged2-59monthschildrenstratifiedaccording
tobasalserumretinolconcentration(200ug/L),thetimetoremissionof3respiratorysignswassignificantlylowerinchildrenwithhigherbasalserumretinolconcentrationsinthe
vitamin A group than in their counterparts in the placebo group
[69.9+49.9
hcomparedwith131.3+143.9h;pvalue=0.049)[BrownN,2004].
-
42
C.Inarandomizedcontrolledtrialinvolving287childrenaged259months,withpneumonia,
no overall differences were observed between the group who
receivedvitaminA50000 IU (aged212mo)or100000 IU (aged1259mo) and
those whoreceivedplacebo[RodriguezA,2005].
D.Among187childrenaged
-
43
Annotation11D.ChestPhysiotherapy
Summaryofthree[3]studiesdidnotdemonstrateanystatisticallysignificantdifferencebetweenthegroupwhohaveundergonechestphysiotherapyandthecontrolgroupastotimetoimprovementinchestxray,andthedurationofthefollowingparameters,namelyfever,coughandhospitalstay(pvalue
-
44
CQ12.Howcanpneumoniabeprevented?
2004ClinicalPracticeGuidelineRecommendation
1.VaccinesrecommendedbythePhilippinePediatricSocietyshouldberoutinelyadministeredtopreventpneumonia[GradeB].
2.Zincsupplementation[10mgforinfantsand20mgforchildrenbeyondtwoyearsofagegivenforatotalof4to6months]maybeadministeredtopreventpneumonia[GradeA].
3.VitaminA[GradeA],immunomodulators[GradeD]andvitaminC[GradeD]shouldnotberoutinelyadministeredasapreventivestrategy.
UPDATEHIGHLIGHTS
1.Ameta-analysisonimmunomodulatorsshowedageneralreductionofratesinacuterespiratorytractinfectionthroughtheuseofimmunostimulants.
2. There are evidences to suggest that handwashing using
antibacterial soaps,pneumococcal and Hib vaccination, elemental
zinc, and breastfeeding areeffectiveinpreventingpneumonia.
3.Singlestudyshowedthatpatientsongastricacidinhibitorsareatanincreaserisktohavepneumonia
Annotation12A.Immunomodulators
InaCochranesystematicreviewinvolvingthirty-fourplacebo-controlledtrials(3877participants)agedlessthan18yearsold,theuseofimmunostimulantswasshownto
reduce rates of acute respiratory infection by 40% (Weighted Mean
Difference
-39.68%;95%CI-47.27%to32.09%).Cautionshouldbeexercisedininterpretingthepossibleadvantageofimmunostimulantbecausethequalityoftrialsthatwereincludedinthemeta-analysiswasgenerallypoor,andahighlevelofstatisticalheterogeneitywasevident[Del-Rio-Navarro,2006].Thenumberneededtopreventis3.
-
45
Annotation12B.Handwashing
Among 600 households who received handwashing promotion with
either
antibacterialsoap[plainsoapwith1.2%triclocarban]orplainsoapversus306householdsas
controls[without handwashing promotion], children younger than 5
years in households thatreceived handwashing promotion and soap had
a 50% lower mean incidence
ofpneumoniathancontrols(-45%95%CI-64%to-26%forantibacterialsoap,and-50%95%CI=65%to-34%forplainsoap)[LubySP,2005].Thenumberneededtopreventis2.
Annotation12C.Vaccine
A.Pneumococcalvaccine
InaCochranesystematicreview,thepooledrelativerisk[RR]forx-rayconfirmed
pneumonia with consolidation (of unspecified etiology) and
clinicalpneumoniawithorwithoutx-rayconfirmationfromtwoarticleswere0.78(95%CI0.69-0.89)andvaccineefficacy[VE]forx-rayconfirmedpneumoniaof22%(95%CI11%-31%)[LuceroMG,2004].
Comparingtheratesin2004withthoseinthebaselineperiodof1997to1999among
children younger than 2 years, hospitalizations due to all-cause
pneumoniadeclinedfrom11.5to5.5per1000children(52.4%decline;p
-
46
Annotation12D.Micronutrients
Inarandomizedcontrolledtrialof1665childrenaged60daysto12monthsold,70mgelemental
zinc given orally once a week for 1 year compared with placebo led
to
asignificantlylowerincidenceofpneumoniainthezincgroupthanintheplacebogroup(RR0.8395%CI0.73-0.95)[BrooksWA,2005].
Annotation12E.Breastfeeding
15,890 infants who were exclusively breastfed had a large and
statistically significantreduction in risk for hospitalization for
lower respiratory tract infection (adjusted
OR:0.66;95%CI:0.470.92)comparedwiththosewhowerenotbreastfed[QuigleyMA,2007].
Annotation12F.Gastricacidinhibitors
Among186GERDpatientsaged8-16monthsoldongastricacid inhibitors
(10
mg/kgranitidineperdaydividedtwicedailyor1mg/kgomeprazoleonceaday)during4monthfollow-up
period, the risk to develop pneumonia is higher among those who are
ongastricacidinhibitors)thancontrols(OR6.39;95%CI:1.3829.70)[CananiRB,2006].
-
47
AppendixADevelopmentProcess
TaskForceonpCAP.TheTaskForceonpCAPareas
follows:CristanQ.Cabanillaas thechairof theTaskForce, Gladys L.
Gillera as the secretary, and Regina M. Canonizado, Anjanette R.
deLeon,RoslynMarieK.Dychiao,BeatrizPraxedesI.ApollaMandanas-Paz,AnnaMarieS.
Putulin, Emily Dolores G. Resurreccion, Ana Maria A. Reyes, Marion
O. Sanchez,Rita Marie Lourdes S. Vergara and Rozaida R. Villon as
members. A pediatricradiologist, Dr Gerado L. Beltran has been
invited to provide insight to radiologicconcerns.There are no
competing interests for any member of the pCAP Task Force except
asguest lecturers or reactors in a pharmaceutical industry
sponsored scientific meetingdealingwiththerapy.
Identificationandappraisalofevidence.SearchstrategieshaveincludedMeSHoneachofthe12clinicalquestionsrunononlinedatabase
[PubMed], the Philippine Pediatric Society publication and
researches
fromeachofthesixPhilippineAcademyofPediatricPulmonologists,Inc.accreditedtrainingprogram
in pediatric pulmonology. Literature search is limited to the
following:
[1]articlespublishedfromJanuary2003toDecember2007;[2]Englishlanguage;[3]3monthsto19yearsofage;[4]andimmunocompetenthost.Inclusionofanarticlewasassessedbyeachsubgrouptobeadequateforappraisal.
ExternalReview.Theupdatehasbeenreviewedbypediatricpulmonologistswhoarenot
involved in
thedevelopmentprocess,andsubsequentlyapprovedbythePAPPBoardofDirectors.
Funding.PAPPhasexclusivelyfundedtheformulationofthisupdate.
Disclaimer.Astheupdatemerelyservestoinformthephysicianofrecentevidence,itisnotintendedtobeastandardofcare.Duetospecificrequirementsimposedbyindividualchildren,thephysician
is advised to exercise personal clinical judgment to the best
interest of thepatient.
-
48
AppendixB.Definitionofterms
Absoluterisk(AR)The probability that an individual will
experience the specified outcome during a
specifiedperiod.Itliesintherange0to1,orisexpressedasapercentage.Incontrasttocommonusage,theword"risk"mayrefertoadverseeventsordesirableevents.
Absoluteriskincrease(ARI)Theabsolutedifferenceinriskbetweentheexperimentalandcontrolgroupsinatrial.Itisusedwhentheriskintheexperimentalgroupexceedstheriskinthecontrolgroup,andiscalculatedbysubtractingtheARinthecontrolgroupfromtheARintheexperimentalgroup.
Absoluteriskreduction(ARR)Theabsolutedifferenceinriskbetweentheexperimentalandcontrolgroupsinatrial.Itisusedwhentheriskinthecontrolgroupexceedstheriskintheexperimentalgroup,andiscalculatedbysubtractingtheARintheexperimentalgroupfromtheARinthecontrolgroup.
BaselineriskTheriskoftheeventoccurringwithouttheactivetreatment.Itisestimatedbythebaselineriskinthecontrolgroup.
Confidenceinterval(CI)The95%confidence interval (or95%confidence
limits)would include95%of results
fromstudiesofthesamesizeanddesigninthesamepopulation.Thisisclosebutnotidentical
tosayingthatthetruesizeoftheeffect(neverexactlyknown)hasa95%chanceoffallingwithintheconfidenceinterval.Ifthe95%confidenceintervalforarelativerisk(RR)oranoddsratio(OR)crosses1,thenthisistakenasnoevidenceofaneffect.
Hazardratio(HR)Broadlyequivalent torelativerisk(RR);usefulwhen
therisk isnotconstantwithrespect
totime.Itusesinformationcollectedatdifferenttimes.Thetermistypicallyusedinthecontextofsurvivalovertime.IftheHRis0.5thentherelativeriskofdyinginonegroupishalftheriskofdyingintheothergroup.
LikelihoodratioThe ratio of the probability that an individual
with the target condition has a specified
testresulttotheprobabilitythatanindividualwithoutthetargetconditionhasthesamespecifiedtestresult.
Meta-analysisA statistical technique that summarises the results
of several studies in a single
weightedestimate,inwhichmoreweightisgiventoresultsofstudieswithmoreeventsandsometimestostudiesofhigherquality.
Negativelikelihoodratio(-LR)Theratiooftheprobabilitythatanindividualwiththetargetconditionhasanegativetestresulttotheprobabilitythatanindividualwithoutthetargetconditionhasanegativetestresult.Thisisthesameastheratio(1-sensitivity/specificity).
Negativepredictivevalue(NPV)Thechanceofnothavingadiseasegivenanegativetestresult.Numberneededtoharm(NNH)
Onemeasureoftreatmentharm.Itistheaveragenumberofpeoplefromadefinedpopulationyouwouldneed
to treatwitha specific interventionforagivenperiodof time
tocauseoneadditionaladverseoutcome.NNHcanbecalculatedas1/ARI.
Numberneededtotreat(NNT)One measureof treatment effectiveness.
It is the average number of people who need to
betreatedwithaspecificinterventionforagivenperiodoftimetopreventoneadditionaladverseoutcomeorachieveoneadditionalbeneficialoutcome.NNTcanbecalculatedas1/ARR.
-
49
Oddsratio(OR)One measure of treatment effectiveness. It is the
odds of an event happening in
theexperimentalgroupexpressedasaproportionoftheoddsofaneventhappeninginthecontrolgroup.
The closer the OR is to one, the smaller the difference in effect
between
theexperimentalinterventionandthecontrolintervention.IftheORisgreater(orless)thanone,thentheeffectsofthetreatmentaremore(orless)thanthoseofthecontroltreatment.Notethattheeffectsbeingmeasuredmaybeadverse(e.g.deathordisability)ordesirable(e.g.survival).WheneventsareraretheORisanalagoustotherelativerisk(RR),butaseventratesincreasetheORandRRdiverge.
Positivelikelihoodratio(+LR)Theratiooftheprobabilitythatanindividualwiththetargetconditionhasapositivetestresulttotheprobabilitythatanindividualwithoutthetargetconditionhasapositivetestresult.Thisisthesameastheratio(sensitivity/1-specificity).
Positivepredictivevalue(PPV)ThechanceofhavingadiseasegivenapositivetestresultPvalue
Theprobabilitythatanobservedorgreaterdifferenceoccurredbychance,ifitisassumedthatthereisinfactnorealdifferencebetweentheeffectsoftheinterventions.Ifthisprobabilityislessthan1/20(whichiswhenthePvalueislessthan0.05),thentheresultisconventionallyregardedasbeing"statisticallysignificant".
Relativerisk(RR)Thenumberoftimesmorelikely(RR>1)orlesslikely(RR
-
50
AppendixC.RiskClassificationforPneumonia-RelatedMortalitya
VARIABLES
PCAPAMinimalrisk
PCAPBLowrisk
PCAPCModeraterisk
PCAPDHighrisk
1.Co-morbidillnessb
None Present Present Present
2.Compliantcaregiverc
Yes Yes No No
3.Abilitytofollow-upc
Possible Possible Notpossible Notpossible
4Presenceofdehydrationd
None MildModerate Severe
5.Abilitytofeed AbleAble Unable Unable6.Age >11mo >11mo
50/min>40/min>30/min
>50/min>40/min>30/min
>60/min>50/min>35/min
>70/min>50/min>35/min
8.Signsofrespfailure
a.Retraction
b.Headbobbingc.Cyanosisd.Gruntinge.Apneaf.Sensorium
None
NoneNoneNoneNoneAwake
None
NoneNoneNoneNoneAwake
Intercostal/subcostalPresentPresentNoneNoneIrritable
Supraclavicular/intercostal/subcostalPresentPresentPresentPresentLethargic/stuporous/comatose
9.Complications[effusion,pneumothorax]
None None Present Present
ACTIONPLANOPDfFollow-upatendoftreatment
OPDfFollow-upafter3days
Admittoregularward
AdmittoacriticalcareunitRefertospecialist
aInthepresenceofoverlappingparameters,assumethenextsevereclassificationevenwithonlyoneparameterpresent.
bComorbidillnessincludesmalnutrition,asthma,congenitalheartdiseaseandotherclinicalconditionsthatcandirectlyaffectrespiratoryfunction.
cNonavailabilityoftheseexternalfactorsnecessitatesadmissionevenifaccompaniedbylesssevereparameters
dGradingofdehydrationadaptedfromNelsonsTextbookofPediatrics1:MILD[thirsty,normalorincreasedpulserate,decreasedurineoutputandnormalphysicalexamination];MODERATE[tachycardia,littleornourineoutput,irritable/lethargic,sunkeneyesandfontanel,decreasedtears,drymucusmembranes,mildtentingoftheskin,delayedcapillaryrefill,coolandpale];SEVERE[rapidandweakpulse,decreasedbloodpressure,nourineoutput,verysunkeneyesandfontanel,notears,parchedmucousmembranes,tentingoftheskin,verydelayedcapillaryrefill,coldandmottled]
eWorldHealthOrganizationagespecificcriteriafortachypnea2
fParentsshouldbeadvisedthatifpatientisrapidlydeteriorating,immediatefollow-upisnecessary
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51
AppendixD.BacterialPneumoniaScore
Predictor
Points
Axillarytemp>39c
3
Age>9months
2
Absoluteneutrophilcount>8,000/mm3
2
Bands>5%
1
Chestxray
Infiltrate
Location
Fluidinpleuralspace
Abscess,bullaeorpneumotocoele
Atelectasis
Well-defined,lobular,segmental,subsegmental[rounded]2pointsPoorlydefined,patchy1pointInterstitial,peribronchial-1point
Singlelobe1pointMultiplelobesinoneorbothlungs,butwell-definedinfiltratesasinabove1pointMultiplesites,perihilar,poorlydefined:-1point
Minimalbluntingofangle1pointObviousfluid2points
Equivocal1pointObvious2points
Subsegmental[usuallymultiplesites]-1pointLobar,involvingRMLorRUL-1pointLobar,involvingotherlobes0point
-3to7
MorenoL,KrishnanJA,DuranP,andFerreroF:DevelopmentandValidationofaClinicalPredictionRuletoDistinguishBacterialFromViralPneumoniainChildren.PediatrPulmonol2006;41:331-337
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52
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