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______________________________________________________________ An Official Publication of the Philippine Academy of Pediatric Pulmonologists, Inc. ______________________________________________________________ PAPP PERSPECTIVE Updates in the Evaluation and Management of Pediatric Community-Acquired Pneumonia PAPP Task Force on pCAP [2008]

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  • ______________________________________________________________

    AnOfficialPublicationofthePhilippineAcademyofPediatricPulmonologists,Inc.

    ______________________________________________________________

    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

  • 3

    CONTENTS

    Foreword

    PrefacetotheUpdatesandAcknowledgement

    2004ClinicalPracticeGuidelineClinicalQuestionswithRecommendations,andUpdateHighlightswithAnnotations

    Appendix

    Bibliography

  • 4

    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

  • 8

    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

  • 10

    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

    ___________________________________________

    *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

  • 11

    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].

  • 12

    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.

  • 13

    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].

  • 16

    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].

  • 17

    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].

  • 18

    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

  • 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

  • 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

  • 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

  • 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].

  • 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.

  • 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%

  • 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%

  • 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.

  • 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].

  • 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.

  • 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

  • 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.

  • 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

  • 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(

  • 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.

  • 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.

  • 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].

  • 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

  • 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

  • 52

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