______________________________________________________________
AnOfficialPublicationofthePhilippineAcademyofPediatricPulmonologists,Inc.
______________________________________________________________
PAPPPERSPECTIVE
Updates
inthe
EvaluationandManagementof
PediatricCommunity-AcquiredPneumonia
PAPPTaskForceonpCAP[2008]
2
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.
5
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.
6
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?
7
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.
9
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.
14
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].
15
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.
19
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
Bibliography
Addo-YoboE.Oralamoxicillinversusinjectablepenicillinforseverepneumoniainchildren aged 3 to 59 months: a randomized multicentre equivalency study.Lancet2004;364:1141-48
AgarwalG.,AwasthiS.,KabraSK.ISCAPStudyGroup.Threedayversusfivedaytreatment with amoxicillin for non-severe pneumonia in young children:amulticentrerandomizedcontrolledtrial.BMJ2004;328;791-796
AlquizaGCabanillaCTheefficacyofambroxolasanadjuncttoamoxicillininchildrenaged3months to19 yearsolddiagnosed withCAP: a randomized,open labeltrial.ThePhilippinePediatricSociety43rdAnnualConventionBookofAbstracts2006;114
AshrafH,JahanS,NurHAlamN,MahmudR,KamalSM,MohammedASalam MA and Gyr N. Day-care management of severe and very severepneumonia without any associated co-morbidities like severe malnutrition in anurbanhealthclinicinDhaka,BangladeshArchDisChild.2007
AtkinsonM.Comparisonoforalamoxicillinandintravenousbenzylpenicillinforcommunity acquired pneumonia in children (PIVOT trial): a multicentrepragmaticrandomizedcontrolledequivalencetrial.Thorax2007;62:1102-1106
AyapJ,ManalaysayM:Outcomeofpatientswithcommunity-acquiredpneumoniatreatedwithchloramphenicol.2002-2005PhilippinePediatricSocietyPhilippinePediatricResearches2006;4192
BambaM,JozakiK,TamaiNSS,IshiharaJ,KoriT,TakeuchiHSY,ChoH,OkanoANY, Kimura K, Nonoyama OKM, Kobayashi I, Sunakawa TKK: Prospectivesurveillance for atypical pathogens in children with community-acquiredpneumoniainJapanJInfectChemother2006;12:3641
BasnetS,AdhikariRKHypoxemiainChildrenwithPneumoniaandItsClinicalPredictorsIndianJPediatr2006;73(9):777-781
BansalA.PenicillinandGentamicintherapyvsAmoxicillin/Clavulanateinseverehypoxemicpneumonia.IndianJournalofPediatrics,2006;73(4):305-309
Bayer-MulsidTBRandomizedclinicaltrialontheeffectofprobiotic,OhiraOMXcapsules as an adjunct in the treatment of severe pneumonia in patients 6-24monthsofagePPSBookofAbstracts2006;131
BlockSL:ComparativeTolerability,SafetyandEfficacyofTabletFormulationsofTwice-Daily Clarithromycin 250 mg versus Once-Daily Extended-ReleaseClarithromycin500mginPediatricandAdolescentPatientsClinPediatr(Phila)2006;45;641
BoseA,ColesCL,Gunavathi,JohnH,MosesP,RaghupathyP,KirubakaranC,BlackRE,BrooksWA,SantoshamM.:Efficacyofzincinthetreatmentof
severepneumoniainhospitalizedchildren
53
BrooksWA,SantoshamM,NaheedA,GoswamiD,WahedMA,Diener-WestM,Faruque AS, Black RE.Effect of weekly zinc supplements on incidence ofpneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial Lancet.2005;366(9490):999-1004
BrooksWA,YunusM,SantoshamM,WahedMA,NaharK,YeasminS,BlackREZinc for severe pneumonia in very young children: double-blind placebo-controlledtrial.Lancet.2004;363(9422):1683-8.
ButunY,KoseS,BabayigitA,OlmezDAnaliO,UzunerN,KaramanO:ChlamydiaandMycoplasma serology in respiratory tract infections of children Tberkloz veToraksDergisi2006;54:254-258
CabanillaC,SantosJ.2006Purposivesamplingquestionnairesurveyastotheutilizationof the 2004 Clinical Practice Guideline in Pediatric Commnity acquiredpneumonia.ConductedduringPreconventionWorkshopandasatellitesymposia43rdPPSAnnualConvention.Unpublished.
CananiRB,PiaCirillo,PaolaRoggero,ClaudioRomano,BasilioMalamisura,,GianlucaTerrin, Annalisa Passariello Francesco Manguso, Lorenzo Morelli, AlfredoGuarino,fortheWorkingGrouponIntestinalInfectionsoftheItalianSocietyofPediatric Gastroenterology, Hepatology and Nutrition (SIGENP): Therapy WithGastric Acidity Inhibitors Increases the Risk of Acute Gastroenteritis andCommunity-AcquiredPneumoniainChildrenPediatrics;2006;117:817-820
CarlosGP,BalitbitLJ,NacpilAL,Lao-AbesamisMB:ComparisonofPenicillinG/Chloramphenicol and cefuroxime in the treatment of pneumonia in children.2002-2005 Philippine Pediatric Society Philippine Pediatric Researches2006;4:187
CarlosCCTheAntimicrobialResistanceSurveillanceProgramProgressReportJanuary-December2003.ResearchInstituteofTropicalMedicine
CarlosCCTheAntimicrobialResistanceSurveillanceProgramProgressReportJanuary-December2004.ResearchInstituteofTropicalMedicine
CarlosCCTheAntimicrobialResistanceSurveillanceProgramProgressReportJanuary-December2005.ResearchInstituteofTropicalMedicine
CarlosCCTheAntimicrobialResistanceSurveillanceProgramProgressReportJanuary-December2006.ResearchInstituteofTropicalMedicine
CastroAV,C.M.Nascimento-Carvalho,F.Ney-Oliveira,C.A.Arajo-Neto,S.C.S.Andrade,L.L.S.LoureiroandP.O.Luz:AdditionalMarkerstoRefinetheWorldHealth Organization Algorithm for Diagnosis of Pneumonia Indian Pediatrics2005;42:773-781
CastroAV,Nascimento-CarvalhoCM,Ney-OliveiraFAraujo-NetoCA,SandraC.AndradeSC:Pulmonary InfiltrateAmongChildrenWithCoughandTachypneaThePediatricInfectiousDiseaseJournal2006;25:757
ChangCC,ChengAC,ChangAB.Over-the-counter(OTC)medicationstoreducecoughasanadjuncttoantibioticsforacutepneumoniainchildrenandadults.CochraneDatabase of Systematic Reviews 2007, Issue 4. Art. No.: CD006088.DOI:10.1002/14651858.CD006088.pub2.
54
ChangAB,PaulJTorzillo,NaomiCBoyce,AndrewVWhite,PeterMStewart,GavinRWheaton,DavidMPurdie,JohnWakermanandPatriciaCValery:Zincandvitamin A supplementation in Indigenous Australian children hospitalised withlower respiratory tract infection:a randomisedcontrolled trialMJA2006;184:107112
ChantryCJ.FullbreastfeedingdurationandassociateddiseaseinrespiratorytractinfectioninUSchildren.Pediatrics.2006Feb;117(2):425-32.
ChiangWC,TeohOH,ChongCY,GohA,TangJP,ChayOM.:Epidemiology,clinicalcharacteristics and antimicrobial resistance patterns of community-acquiredpneumoniain1702hospitalizedchildreninSingaporeRespirology.2007;12:254-61
CherianT,MulhollandK,CarlinJB,OstensenH,AminR,deCampoM,GreenbergD,LagosR,LuceroM,MadhiSA,OBrienKL,ObaroS,SteinhoffMC,andtheWHORadiologyWorkingGroup:StandardizedinterpretationofpaediatricchestradiographsforthediagnosisofpneumoniainepidemiologicalstudiesBulletinoftheWorldHealthOrganization2005;83:353-359
deAndradeAL,JooGuimaresdeAndrade,CelinaMariaTurchiMartelli,SimonneAlmeida de Silva, Renato Maurcio de Oliveira, Maria Selma Neves Costa,Cristina Borges Laval, Luiza Helena Vilela Ribeiro and Jose Luis Di Fabio:Effectiveness of Haemophilus influenzae b conjugate vaccine on childhoodpneumonia:acase-controlstudyinBrazilInternationalJournalofEpidemiology2004;33:173181
deFatimaM,SantAnnaMarch,CC.SignsandsymptomsindicativeofCAPinInfantsundersixmonths.BrazilianJournalofInfectiousDiseases2005;9:150-155
deJesus-OabelBAandAtienza-deLeonMN,Knowedge,attitudeandpracticeofphysicians of the North Integrated Residency Training on the diagnosis andmanagementofcommunity-acquiredpneumoniainchildren.2008.Unpublished.
Del-Rio-NavarroBE,EspinosaRosalesF,FlenadyV,Sienra-MongeJ.Immunostimulantsforpreventingrespiratorytractinfectioninchildren.CochraneDatabaseSystRev.2006Oct18;(4):CD004974.delaCruzR,deGuzmanD,CabanillaC,SantosJ:Clinicalindicespredicting
pneumonia.PhilippineChildrensMedicalCenterBookofAbstracts2007;189DonM,FasoliL,PaldaniusM,MarjaanaKleemolaRV,RaTyR,LeinonenM,Korppi
M, Tenore A and Canciani M: Aetiology of community-acquired pneumonia:Serological results of a paediatric survey Scandinavian Journal of InfectiousDiseases2005;37:806-812
DonM,ValentF,KorpppiM,FalletiE,deCandiasA,FasoliL,TenoreiAandCancianiMEfficacyofserumprocalcitonininevaluatingseverityofcommunity-acquired pneumonia in childhood. Scandinavian Journal of Infectious Diseases,2007;39:129-137
EnarsonP,EnarsonD,GieRInternationalUnionAgainstTuberculosisandLungDisease.Managementofthechildwithcoughordifficultbreathing:AGuideForLowIncomeCountries2ndEd2004
ErquizaGS,Ochoa-RagazaRS,ReleyMandJiaoAQ:TheeffectofvirgincoconutoilsupplementationforCAPinchildrenaged3-60monthsadmittedatthePhilippinechildrensMedicalCenter:asingleblindedRCT.PhilippineChildrensMedicalCenter.Unpublished
55
EspositoS,AlessandroLizioli,AnnalisaLastrico1,EnricaBegliatti,AlessandroRognoni,ClaudiaTagliabue,LauraCesati1,VittorioCarreriandNicolaPrincipi:Impactonrespiratory tract infections of heptavalent pneumococcal conjugate vaccineadministeredat3,5and11monthsofageRespiratoryResearch2007,8:12:1-9
FonsecaF,HoppuK,ReyLC,AmaralJ,QaziS:ComparingPharmacokineticsofAmoxicillin Given Twice or Three Times per Day to Children Older than 3MonthswithPneumoniaAntimicrobAgentsChemother2003;47:997-1001
GarciaMC,deOcampoJ,MaraionoJ:ClinicalandradiologicvariationsofMycoplasma pneumoniae in children Philippine Pediatric Society PhilippinePediatricResearches2002-2005;186
GavranichJB,ChangAB.Antibioticsforcommunityacquiredlowerrespiratorytractinfections (LRTI) secondary to Mycoplasma pneumoniae in children. CochraneDatabase of Systematic Reviews 2005, Issue 3. Art. No.: CD004875.DOI:10.1002/14651858.CD004875.pub2.
GilchristFJ:Istheuseofchestphysiotherapybeneficialinchildrenwithcommunity-acquired pneumonia?Arch. Dis. Child. online 27 Jul 2007; doi: 10.1136/adc.2007.127290
GotosLV,CabanillaC,SantosJ:RandomizedstudyonsalbutamolornormalsalinesolutionasnebulizingsolutionversusnotreatmentamongpatientsadmittedwithpCAP at Philippine Childrens Medical Center. The Philippine Journal ofPediatrics2004;53:165-170
GuppyMPB,MickanSM,DelMarCB.Advisingpatientstoincreasefluidintakefortreating acute respiratory infections. Cochrane Database of Systematic Reviews2005,Issue4.Art.No.:CD004419.DOI:10.1002/14651858.CD004419.pub2.
HazirT,NisarYB,QaziSA,KhanSF,RazaM,ZameerSandMasoodSA:Chestradiographyinchildrenaged2-59monthsdiagnosedwithnon-severepneumoniaas defined by World Health Organization descriptive multicentre study inPakistanBMJ2006;333;629-633
HazirT,QaziSA,NisarB,S.Maqbool,R.Asghar,I.Iqbal,S.Khalid,S.Randhawa,S.Aslam,S.Riaz,S.Abbasi:CanWHOtherapyfailurecriteriafornon-severepneumoniabeimprovedinchildrenaged259months?IntJTuberclLungDis2006;10:924931
HazirT.Comparisonofstandardversusdoubledoseofamoxicillininthetreatmentofnon-severepneumoniainchildrenaged2-59months:amulti-centre,doubleblind,randomizedcontrolledtrialinPakistan.ArchDisChild2007;92;291-297
HuangHH,.ZhangYY,XiuQY,ZhouXHuangSGQ,WangDM,WanF:Community-acquired pneumonia in Shanghai, China: microbial etiology andimplications for empirical therapy in a prospective study of 389 patients Eur JClinMicrobiolInfectDis2006;25:369374
HussainH,WatersH,OmerSB,KhanA,BaigIY,MistryRandHalseyNThecostoftreatmentforchildpneumoniasandmeningitisintheNorthernAreasofPakistanIntJHealthPlannMgmt2006;21:229238.
JuvenT,RuuskanenOandMertsolaJ:Symptomsandsignsofcommunity-acquiredpneumoniainchildrenScandJPrimHealthCare2003;21:5256.
56
KabraSK,LodhaR,PandeyRM.Antibioticsforcommunityacquiredpneumoniainchildren. Cochrane Database of Systematic Reviews2006, Issue 3. Art. No.:CD004874.DOI:10.1002/14651858.CD004874.pub2.
KafetzisA,ConstantopoulosA,andPapadopoulosNG:Etiologyofcommunity-acquiredpneumonia in hospitalized school-age children: evidence for high prevalence ofviralinfectionsClinicalInfectiousDiseases2004;39:6816
KaiserL,WatC,MillsTM.:ImpactofOseltamivirTreatmentonInfluenza-RelatedLowerRespiratoryTractComplicationsandHospitalizations. Arch InternMed.2003;163:1667-1672.
KoganR,MartinezA,RubilarL,PayaE,QuevedoI,PupoH,Klgo,GiradiGandCastro-Rodriquez JA: Comparative Randomized Trial of Azithromycin VersusErythromycin and Amoxicillin for Treatment of Community-AcquiredPneumoniainChildrenPediatricPulmonology2003;35:9198
KorppiM:Non-specifichostresponsemarkersinthedifferentiationbetweenpneumococcal and viral pneumonia: What is the most accurate combination ?PediatricsInternational2004;46:545550
LoveraD,ArboA.Treatmentofchildhoodcomplicatedcommunity-acquiredpneumoniawithamoxicillin/sulbactamJChemother.2005;17:283-8
LubySP,AgboatwallaM,FeikinDR,PainterJ,BillhimerW,AltafA,HoekstraRM.Effect of handwashing on child health: a randomised controlled trial. Lancet.2005;66(9481):225-33.
LuceroMG,DulaliaVE,ParrenoRN,Lim-QuianzonDM,NohynekH,MakelaH,Williams G. Pneumococcal conjugate vaccines for preventing vaccine-typeinvasive pneumococcal disease and pneumonia with consolidation on x-ray inchildrenundertwoyearsofage.CochraneDatabaseofSystematicReviews2004,Issue4.Art.No.:CD004977.DOI:10.1002/14651858.CD0049
LupisanSP,RuutuP,Abucejo-LadesmaBP,etalPredictorsofdeathfromseverepneumonia among children 2-59 months old hospitalized in Bohol:implicationsfor referral criteria at a first-level health facility Trop Med Int Health. 2007;12(8):962-71
LynchT,PlattR,GouinS,LarsonCandPatenaudeY.Canwepredictwhichchildren with clinically suspected pneumonia will have the presence of focalinfiltratesonchestradiograph?JournalofPediatrics2004;113;3186-e189
Mahabee-GittensEM,Grupp-PhelanJ,BrodyAS,DonnellyLF,AllenBraceySE,DumaEM,MalloryMLandSlapGB:Identifyingchildrenwithpneumoniaintheemergencydepartment.ClinPediatr(Phila),44(5):427-35,2005
MahalanabisD,MadhurimaLahiri,DilipPaul,SushamGupta,AtulGupta,MohammedA Wahed, and Mohammed A Khaled: Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A ininfants and young children with severe acute lower respiratory infection Am JClinNutr2004;79:4306
MahalanabisD,BasakM,PaulD,GuptaS,ShaikhS,WahedMA,KhaledMA .AntioxidantvitaminsEandCasadjuncttherapyofsevereacutelower-
respiratoryinfectionininfantsandyoungchildren:arandomizedcontrolledtrial.EurJClinNutr.2006;60(5):673-80.
57
MarquezWCabanillaCCotromoxazolecomparedwithamoxicillinasswitchtherapyinmoderateriskpediatriccommunity-acquiredpneumonia:arandomizedcontrolledtrial.The Philippine Pediatric Society, Inc. 44th Annual Convention ResearchPaperAbstract.2007;104
MathesonNJ,HarndenAR,PereraR,SheikhA,Symmonds-AbrahamsM.:Neuramidaseinhibitors forpreventingand treating influenza inchildren (Review). CochraneDatabaseofSystematicReviews2007,Issue1.ArtNo.:CD002744.
MichelowI,OlsenK,LozanoJ,RollinsNK,DuffyLB,ZieglerT,KauppilaJ,LeinonenMandMcCrackenGHEpidemiologyandclinicalcharacteristicsofcommunity-acquiredpneumoniainhospitalizedchildrenPediatrics2004;113;701-707
MohamedAzmiAhmadHasali,MohamedIzhamMohamedIbrahim,SyedAzharSyedSulaiman, Zhar i Ahmad and J ameela Banu Ahmad Hasal i A clinical andeconomic study of community-acquired pneumonia between single versuscombinationtherapyPharmWorldSci2005;27:249253
MorenoL,KrishnanJA,DuranP,andFerreroF:DevelopmentandValidationofaClinical Prediction Rule to Distinguish Bacterial From Viral Pneumonia inChildren.PediatrPulmonol2006;41:331-337.
MorozumiM:SimultaneousDetectionofPathogensinClinicalSamplesfromPatientswith Community-Acquired Pneumonia by Real-Time PCR with Pathogen-Specific Molecular Beacon Probes Journal of Clinical Microbiology2006,44:14401446
MorozumiM,HasegawaK,KobayashiR,InoueN,IwataS,KurokiH,KawamuraN,NakayamaE,TajimaT,ShimizuK,UbukataK.Emergenceofmacrolide-resistantMycoplasmapneumoniaewitha23SrRNAgenemutationAntimicrobAgentsChemother.2005;49:2302-6
NiJ,WeiJ,WuT.VitaminAfornon-measlespneumoniainchildren.CochraneDatabaseSystRev.2005Jul20;(3):CD003700
NunesA,CamargosP,CostaPCamposTK:AntigenDetectionfortheDiagnosisofPneumoniaPediatricPulmonology2004;38:135139
OthmanN,DIsaacsandAKesson1:MycoplasmapneumoniaeinfectionsinAustralianchildrenJ.Paediatr.ChildHealth2005;41,671676
Ochoa-RagazaS,GotosLV,CabanillaC,SantosJ:Apreliminarystudyonswitchtherapy among patients with pCAP The Philippine Journal of Pediatrics2004;53:198-204
OcbinaPollienetteJR,CabanillaC.Accuracyoftheclinicalpredictorsofcommunity-acquired pneumonia in Filipino Children aged 5-12 years old.PhilippinePediatricSocietyBookofAbstracts2006:140
PaintsilE:Pediatriccommunity-acquiredmethicillin-resistantStaphylococcusaureusinfection and colonization: trends and management Curr Opin Pediatr2007;19:7582
PabloBrockmannV.,XimenaIbarraG.,IgnaciaSilvaW.yTamaraHirschB.Etiology of acute fever without source in infants consulting at an emergencydepartmentRevChilInfect2007;24(1):33-39
PhilHealth,HealthTechnologyAssessmentUnit,QualityAssuranceResearchandPolicyDevelopmentGroupHTAForum2006;44[1]:4
58
PhilippineHealthInsuranceCorporation,ClaimspaymentsummaryforCY2006ages0-19forpneumonia.Personalcommunication
PocsidioC,MelgarT,BeltranR,CabanillaC.OutcomeofpatientswithpCAPevaluatedandmanagedusingtheriskclassificationschemeofthePPS2004CPGPhilippineChildrensMedicalCenter.Unpublished
PradaC,CabanillaC:Causesofearlytreatmentfailureamonghospitalizedpatients with pCAP. Philippine childrens Medical Center Book of Abstracts2007;192
PurcellK,MD,PharmD,MHA;FergieJ,MD.EpidemicofCommunity-Acquired Methicillin-ResistantStaphylococcusaureusInfections.A14-YearStudyat DriscollChildrensHospital.ArchPediatrAdolescMed.2005;159:980-985PurcellK,FergieJ:LackofUsefulnessofanAbnormalWhiteBloodCellCountfor
PredictingaConcurrentSeriousBacterialInfectioninInfantsandYoungChildrenHospitalizedWithRespiratorySyncytialVirusLowerRespiratoryTractInfectionPediatrInfectDisJ2007;26:311315
QuigleyMA:Breastfeedingandhospitalizationfordiarhealandrespiratoryinfectionin theUnitedKingdomMilleniumCohortStudy.Pediatrics.2007 Apr;119(4):e837-42.RattanadilokNa,BhuketT,NawanoparatkulS,SuwanjuthaS,Teeyapaiboonsilpa
P.Economicburdeninmanagementofacutelowerrespiratoryinfection,patientsperspective:acasestudyofTakhliDistrictHospital.2002JMedAssocThai85(Suppl.4):S12411245.
RudanI,TomaskovicL,Boschi-PintoC,CampbellHonbehalfofWHOChildHealthEpidemiologyReferenceGroupGlobalestimateoftheincidenceofclinicalpneumoniaamongchildrenunderfiveyearsofageBulletinoftheWorldHealthOrganization2004;82:895-903.
RequejoHI.Community-AcquiredPneumoniaintheChildhood:AnalysisoftheDiagnosticMethodsTheBrazilianJournalofInfectiousDiseases2007;11:246-248.
RequejoH,CocozaMAC-ReactiveProteinintheDiagnosisofCommunity-AcquiredPneumoniaTheBrazilianJournalofInfectiousDiseases2003;7:241-244
RodrguezA,DavidsonHHamer,JosRivera,MarioAcosta,GildaSalgado,MarthaGordillo, Myryam Cabezas, Carlos Naranjo-Pinto, Julio Legusamo, DinorGomez,GuillermoFuenmayor,Edgar Jativa,GladysGuaman,BerthaEstrella,andFernandoSemprteguiEffectsofmoderatedosesofvitaminAasanadjunctto the treatment of pneumonia in underweight and normal-weight children: arandomized,double-blind,placebo-controlledtrialAmJClinNutr2005;82:10906.
RomuloAC,Lomibao-SantosMAA,MarceloMJ,CabanillaCQ,SantosJRandomizedtrialcomparingtheefficacyandsafetyoforalamoxicillinanderythromycininthetreatmentofpCAPinanambulatorysetting.PCMC,2006[Unpublished]
RattanadilokNa,BhuketT,NawanoparatkulS,SuwanjuthaS,TeeyapaiboonsilpaP.Economicburdeninmanagementofacutelowerrespiratoryinfection,patientsperspective:acasestudyofTakhliDistrictHospital.2002JMedAssocThai85(Suppl.4):S12411245.
59
RudanI,TomaskovicL,Boschi-PintoC,CampbellHonbehalfofWHOChildHealthEpidemiology Reference Group Global estimate of the incidence of clinicalpneumoniaamongchildrenunderfiveyearsofageBulletinoftheWorldHealthOrganization2004;82:895-903.
Sadang-SaguinsinS,Yu-GoO,Ochoa-Rag
Top Related