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2
CONTENTS
Preface
Introduction
Methodology Overview
Disclaimer
Update Recommendations
Clinical Questions
Background: 2nd PAPP Update [2012]
Recommendations
3rd PAPP Update [2016] Recommendations
Summary of Evidence
Bibliography
Appendix
3
PREFACE
The Philippine Pediatric Society in 2004 spearheaded the publication of the Clinical Practice Guideline
in the Evaluation and Management of Pediatric Community-acquired P n e u m o n i a [pCAP]. Because of
the important, unresolved issues and concerns on pCAP in the following years, the Philippine
Academy of Pediatric Pulmonologists [PAPP] drafted the first Update in the Evaluation and
Management of pCAP in 2008. Revisions on several recommendations b a s e d on recent evidences
from local and foreign literature were published in the second PAPP Update in 2012. The PAPP Task
Force on pCAP in 2016 felt the need to come up with the third Update on pCAP to include new
developments on recommendations in the evaluation and management of childhood pneumonia.
It is our hope that this recent update will assist and guide clinicians in the management o f pCAP
thereby improving the quality of health care for Filipino children.
4
INTRODUCTION
Similar to the 2008 and 2012 PAPP Updates in Pediatric Community-acquired Pneumonia, the 2016 PAPP
Update is anchored on a framework that is primarily intended for individual clinical practice. In reviewing the
current body of evidence, such framework has focused on identifying clinically important outcomes for each
clinical question, and expressing the impact of harm and benefit of each intervention in numerical values
whenever possible. While the former is universal, the latter can be applied on a case-to-case basis irrespective of
recommendation.
Three limitations of the current update have to be mentioned. First, because of limited funding and logistics, there
is failure to include cost-benefit ratio of each diagnostic, therapeutic or preventive intervention [which is important
considering that most financial transactions are out-of-pocket in most resource-limited situations]. There is similar
failure to address the issue of availability of interventions in the local setting [which is equally important
considering that some of these are only available in selected medical centers nationwide]. Second, there is a
considerable lack of epidemiologic data, and patient-outcome oriented and knowledge-gap directed body of
researches reported in the local setting, both of which could have provided basis for stronger recommendations.
And third, there is currently no neutral national clearing house outside of PAPP that could have provided initial
guidance and subsequent peer review in developing the guideline update.
th
In preparation for the 4 PAPP Update [2020], these limitations, which potentially can lead to barriers in
Implementation, have to be addressed to narrow the policy-practice gap among local practitioners.
nd rd
Key differences between the 2 and 3 Updates are summarized below.
SECTION KEY DIFFERENCES
2012 2016
A. Methodology
1. Microbial etiology Virus, bacteria and Mtb Virus and bacteria
2. Geographic distribution of
MetroManila MetroManila, MetroCebu and MetroDavao
Task force membership
3. Literature review Jan 2008 to Dec 2011 Jan 2012 to Dec 2016
4. Definition of level of Based on Sacket DL,
evidence and grading Straus SE: Evidence Developed by the 2016 PAPP Task Force in pCAP
of recommendation Based Medicine 2000
5. Geographic distribution of MetroManila Nationwide
stakeholders
B. Summary recommendations
1. Appraisal
1. Predictors to detect radiographic pneumonia
a. Higher threshold for Sa02
Clinical Question1 b. Additional indeces
2. Addition of negative predictors for radiographic pCAP
3. Revised indications for requesting chest xray at initial
site-of-care
Clinical Question 2 No significant change
Clinical Question 3 No significant change
Clinical Question 4 1. Addition of lung ultrasound and anaerobic culture
as diagnostic tests
2. Removal of diagnostic test for tuberculosis
Clinical Question 5 1. Additional test to determine necessity of antibiotic
administration
2. No recommendation for pCAP A or B
2. Therapeutic approach
Clinical Question 6 No significant change
Clinical Question 7 Addition of zanamivir
Clinical Question 8 Addition of deifinition of clinical stability
Clinical Question 9 No significant change
Clinical Question 10 No significant change
Clinical Question 11 Zinc may be beneficial
3. Preventive strategies
Clinical Question 12 Zinc may not be beneficial
5
METHODOLOGY OVERVIEW
A. Scope
The 3rd PAPP Update in the Evaluation and Management of Pediatric Community-acquired Pneumonia [2016]
is limited to clinical recognition of radiographic community-acquired pneumonia, identification of appropriate
and practical diagnostic procedures, and initiation of rational management and preventive measures in an
immunocompetent patient aged 3 months to 19 years. It does not include recurrent, persistent, aspiration or
ventilator-associated pneumonia, and infection caused by tuberculosis, parasite, fungus or etiologic agent
acquired from a healthcare facility.
D. Conflict of interest
The following have been resource speakers in continuing medical education activities dealing with pediatric
community-acquired pneumonia sponsored by a pharmaceutical company, a medical society, or a hospital
facility: Vivian A. Ancheta, Gari D. Astrologio, Janet C. Bernardo, Alfredo L. Bongo, Janet Myla Q. Bonleon,
Cristan Q. Cabanilla, Lydia K. Chang, Edward A. Chua, Julie Iris C. Clapano, Amelia G. Cunanan, Beverly D.
de la Cruz, Anjanette R. de Leon, Yadnee V. Estrera, Jean Marie E. Jamero, Arnold Nicholas T. Lim, Grace V.
Malayan, Beatriz Praxedez Apolla I. Mandanas, Raymund Anthony L. Manuel, Vicente Carlomagno D.
Mendoza, Doris Louise C. Obra, Catherine S. Palaypayon, Cynthia Theresa M. Rimando, Emily B. Gaerlan-
Resurreccion, Ernesto Z. Salvador, Marion O. Sanchez, Josy Naty M. Venturina, Rozaida R. Villon, Nilyn
Elise O. Ygnacio, and Dahlia L. Yu.
6
G. Reporting of results of studies in the Summary of Evidence
The results of studies as reported in the Summary of Evidence are outlined to include subject population, study
design, an endpoint considered to be clinically important by the 2016 Task Force to the practitioner,
and numerical result.
I. Stakeholder’s consultation
Results of questionnaire surveys on pCAP among participants of the PAPP annual convention from 2012-2015
were reviewed and taken into consideration in developing the current guideline.
In addition, a preliminary draft was sent to the following medical stakeholders [who were preselected by the
Task Force] for individual evaluation as to clarity, acceptability and applicability in individual clinical practice:
Philippine Pediatric Society board-certified pediatrician [generalist, infectious disease and ambulatory], general
medical practitioner, rural health physician, pediatric radiologist, pathologist, and postgraduate trainee in
general pediatrics. Gratitude is extended to the following stakeholders for reviewing the document and
providing invaluable comments: Marjorie Grace M. Apigo, Genevieve G. Arenilo, Joseph I. Brazal, Marie Aimee
Hyacinth V. Bretaña, Elia P. Cabrera, Ma. Theresa L. Carin. Jan Kamille R. Coronel, Eva D. de Leon, Angelo
Don S. Grasparil II, Anna Samantha D. Imperial, Jonathan G. Lim, Jo-anne J. Lobo, Marian Carmela B. Magno,
Angel Andrea M.Mendoza, Arcelin L. Piramide, Merfelito B. Ramolete, Yvonne B. Redoble, Maria Leah C.
Rivera, Maja Kristina J. Ruiz, Jaime A. Santos, Maria Araceli F. Torrenueva, and Belinda B. Ycong.
Any opinion expressed by the individual stakeholder did not necessarily reflect that of the medical society or
institution he/she is affiliated with.
L. Source of funding
Internal funding was provided by the Philippine Academy of Pediatric Pulmonologists, Inc. There were no
sources for external funding.
7
DISCLAIMER
The recommendations presented in this update are limited to options in the evaluation,
management and prevention of community-acquired pneumonia in an immunocompetent
patient aged 3 months to 19 years. Each recommendation should not be presumed to be
applicable to all patients. It is meant to complement but never replace individual clinical
judgement.
8
3rd PAPP GUIDELINE UPDATE RECOMMENDATIONS [2016]
IN
Clinical Questions
Subcommittee Members
Summary of Evidence
9
Clinical Question 1. WHO SHALL BE CONSIDERED AS HAVING COMMUNITY-ACQUIRED PNEUMONIA?
SUBCOMMITTEE MEMBERS
Anjanette R. de Leon
Vicente Carlomagno D. Mendoza
Josy Naty M. Venturina
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. The presence of pneumonia may be considered even without a chest radiograph in a patient presenting with cough and/or
respiratory difficulty [Recommendation Grade D] plus any of the following predictors of radiographic pneumonia:
1.1. At the Emergency Room as the site-of-care,
1.1.1. tachypnea as defined by World Health Organization in a patient aged 3 months to 5 years [Recommendation Grade B]; or
1.1.2. fever at any age [Recommendation Grade B]; or
1.1.3. oxygen saturation < 92% at room air at any age [Recommendation Grade B] in the absence of any coexisting illness
(neurologic, musculoskeletal, or cardiac condition) that may potentially affect oxygenation [Recommendation Grade D].
1.2. At the Out-Patient Clinic as the site-of-care,
1.2.1. tachypnea as defined by World Health Organization in a patient aged 3 months to 5 years [Recommendation Grade D]; or
1.2.2. fever at any age [Recommendation Grade D].
2. The presence of pneumonia should be determined using a chest radiograph in a patient presenting with
2.1. cough and/or respiratory difficulty [Recommendation Grade D] in the following situations:
2.1.1. presence of dehydration aged 3 months to 5 years [Recommendation Grade B].
2.1.2. presence of severe malnutrition aged less than 7 years [Recommendation Grade B].
2.2. high grade fever and leukocytosis aged 3 to 24 months without respiratory symptoms [Recommendation Grade C].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of current grading of recommendation.
10
SUMMARY OF EVIDENCE
1. Reference standard
nd
The 2016 PAPP Task Force on pCAP has retained the position statement of the 2012 PAPP 2 pCAP Update,
that chest x-ray is the reference standard in establishing the presence [or absence] of pneumonia. The Task
Force similarly acknowledges the limitations of chest x-ray as a diagnostic tool. There are no studies evaluating
its accuracy in comparison with microbiology as the gold standard. In addition, moderate reliability exists as to
interobserver variability in radiographic interpretation [Neuman M,2012].
2. Initial presentation
The Task Force has retained the position statement of the 2012 Update that a patient presenting initially with
symptoms of cough and/or respiratory difficulty may be evaluated for possible presence of pneumonia. Using
this presentation, the potential risk for the presence or absence of radiographic pneumonia is shown below.
PATIENTS RADIOGRAPHIC PNEUMONIA
INITIAL PRESENTATION AGE AUTHOR/YEAR
[n] Positive Negative
Emergency room as the site of care
Cough or difficulty of breathing 147 58% 42% Modi P,2013
Cough or difficulty of breathing <5y
and --- Wingerter S,2012
324 34%
WHO-defined, age-specific tachypnea
11
3.2. Negative predictors
PATIENTS
PREDICTOR AGE SENSITIVITY AUTHOR/YEAR
[n]
Emergency room as site-of-care
1
Oxygen saturation
<94% 86%
Clinical presentation
Fever 93%
Nasal flaring 91%
Chest wall retractions 147 <5y 81-85%
Modi P,2013
Decreased breath sounds 70%
Wheezing 44%
Grunting 40%
Tachypnea
37%
[WHO defined. age-specific]
Emergency room or ward as site-of-care
2
Lung ultrasound
Consolidation 765 <18y 96% (94%–98%) Pereda M,2013
1
Determination of oxygen saturation at room air is desirable in situation where pulse oximeter is available.
2
Subgroup meta-analysis. Advantages of lung ultrasound as an alternative to chest radiograph in patients include detection of pleural
effusion at site-of-care where chest x-ray is not readily available, or in a situation where legal guardians want to avoid ionizing
radiation. The main disadvantage is that it is operator dependent.
12
Clinical Question 2. WHO WILL REQUIRE ADMISSION?
SUBCOMMITTEE MEMBER
Rozaida R. Villon
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. Revised risk classification for pneumonia-related mortalitya [Recommendation Grade D]
CLASSIFICATION PROVIDED BY
PhilippineAcademy of Pediatric Pulmonologists, Inc pCAP A or B pCAP C pCAP D
Philippine Health Insurance Corporation --- Pneumonia I Pneumonia II
World Health Organization Nonsevere Severe Very severe
b
VARIABLES
Clinical
1. Dehydrationc None Mild Moderate Severe
2. Malnutritiond None Moderate Severe
3. Pallor None Present Present
e
4. Respiratory rate a. 3 to12 months >50/min to <60/min >60/min to <70/min >70/min
b. 1 to 5 yearse >40/min to <50/min >50/min >50/min
c. >5 years >30/min to <35/min >35/min >35/min
5. Signs of respiratory failure a. Retraction None Intercostal / subcostal Supraclavicular / IC / subcostal
b. Head bobbing None Present Present
c. Cyanosis None Present Present
d. Grunting None None Present
e. Apnea None None Present
f. Sensorial changes None Irritable Lethargic / stuporous / comatose
f
Diagnostic aid at site-of-care
1. Chest x-ray findings of any of the following: effusion; None Present Present
abscess; air leak or lobar consolidation
2. Oxygen saturation at room air using pulse oximetry 95% <95% <95%
ACTION PLAN
1. Site-of-care Outpatient Admit to ward Admit to a critical care facility
2. Follow-up End of treatment
a
In order to classify to a higher risk category, at least 2 variables (clinical and diagnostic aid) should be present. In the absence of a diagnostic aid variable, clinical variables will suffice.
b
Risk factors for mortality based on evidence and/or expert opinion among members of the 2012 PAPP Task Force on pCAP.
c
Weight for Height SD score< -2 moderate; SD score< -3 severe. WHO management of severe malnutrition: a manual for physicians and other health workers. Geneva. WHO 1999.
d
Grading of dehydration adapted from Nelson’s Textbook of Pediatrics: MILD [thirsty, normal or increased pulse rate, decreased urine output and normal physical examination];
MODERATE [tachycardia, little or no urine output, irritable/lethargic, sunken eyes and fontanel, decreased tears, dry mucus membranes, mild tenting of the skin, delayed capillary
refill, cool and pale]; SEVERE [rapid and weak pulse, decreased BP, no urine output, very sunken eyes and fontanel, no tears, parched mucous membranes, tenting of the skin, very
delayed capillary refill, cold and mottled].
e
World Health Organization age-specific criteria for tachypnea for children under 5 years old.
f
Chest x-ray and pulse oximetry are desirable variables but not absolutely necessary as determinants of admission at site-of-care.
2. Patients under 5 years old [Recommendation Grade B] and more than 5 years old [Recommendation Grade D] who are classified as
pCAP C but whose chest x-ray is without any of the following: effusion, lung abscess, air leak or multilobar consolidation, and
whose oxygen saturation is >95% at room air can be managed initially on an outpatient basis.
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of current grading of recommendation.
13
2. Central nervous system signs
2.1. Altered sensorium None Irritable Lethargic / stuporous / comatose
2.2. Convulsion None Present Present
3. Circulatory signs
3.1. Poor perfusion None Capillary refill >3s Shock
3.2. Pallor None Present Present
4. General considerations
4.1. Malnutrition4 None Mild No Moderate Severe
4.2. Inability to drink No Present Yes Yes
4.3. Comorbid conditions None Present Present
Ancillary parameters5
5. Chest x-ray findings of effusion,
abscess, air leak or multilobar None Present Present
consolidation
6. Oxygen saturation at room air using
95% 91% to 94% <90%
pulse oximetry
4
Weight for Height [WFH] SD score < -2 moderate; SD score < -3 severe. WHO management of severe malnutrition: a manual for
physicians and other health workers. Geneva. World Health Organization 1999.
5
Chest x-ray and pulse oximetry are desirable variables but not necessary as determinants of admission at site-of-care.
2. A patient initially classifed as pCAP A or B but is not responding to current treatment after 48 hours may
be admitted [Recommendation Grade D].
3. A patient classified as pCAP C may be
3.1. admitted to the regular ward [Recommendation Grade D].
3.2. managed initially on an outpatient basis [Recommendation Grade C2] if all of the following are not
present at initial site-of-care [Recommendation Grade D].
3.2.1. Age less than 2 years old.
3.2.2. Convulsion.
3.2.3. Chest x-ray with effusion, lung abscess, air leak or multilobar consolidation.
3.2.4. Oxygen saturation < 95% at room air.
4. A patient classified as pCAP D may be admitted to a critical care unit [Recommendation Grade D].
SUMMARY OF EVIDENCE
1. Risk classification scheme
The Task Force has maintained the previous risk classification scheme for pneumonia-related mortality from the
PAPP 2012 Clinical Practice Guideline in the Evaluation and Management of pCAP with minor modifications.
2. Individual risk factors for subsequent mortality within 48 hours at initial site-of-care.
STUDY DESCRIPTION ODDS RATIO P
RISK FACTORS n/N [%] AUTHOR/YEAR
DESIGN AGE [95%CI] VALUE
1
49/85 [57.6%] 1.85 (1.03-3.32) 0.020 Ramachandran P,2012
Severe malnutrition 1.91 (0.67–4.92) 0.230 Agweyu A,2014
1.37 (0.35–5.31) Webb C, 2012
22/85 [25.9%] 14.49 (4.49-51.88) 0.001 Ramachandran P,20121
Altered consciousness
1.02 (0.40–2.59) 0.970 Agweyu A,2014
<59m 11.15 (3.38-40.59) 0.001 Ramachandran P,20121
Convulsion
6.83 (2.01–23.2) Webb C 2012
1
Cohort 1 to 6m 49/85 [57.7%] 2.77 (1.57-4.91) 0.001 Ramachandran P,2012
Age
2 to11m 1.80 (0.57–5.67) 0.310 Agweyu A,2014
Shock 9.99 (3.36–29.7) Webb C,2012
4/85 [4.7%] 0.51 (0.14-1.72) 0.230 Ramachandran P,20121
2
<12y Increasing severity 3.20 (1.20-8.90) 0.020 Ferreira S,2014
Inability to drink 6.39 (1.40–29.23) 0.006 Agweyu A,2014
1
Congenital heart disease 10/85 [11.8%] 5.53 (1.53-21.72) 0.001 Ramachandran P,2012
Head nodding 2.15 (0.84–5.50) 0.100
<59m Central cyanosis 1.85 (0.56–6.08) 0.300 Agweyu A,2014
Grunting 0.71(0.27–1.86) 0.490
SpO2 <90% 0.31 (0.07–1.42) 0.110
1 2
Radiologic pneumonia cases Multivariate analysis
3. Composite risk factors for subsequent mortality within 48 hours at initial site-of-care
This is a gap in current knowledge. There are no published data available for review.
4. Management of pCAP C on an outpatient basis
STUDY DESCRIPTION MORTALITY TREATMENT FAILURE RATE
INTERVENTION AUTHOR/YEAR
DESIGN AGE RATE AT DAY 14
7 days oral amoxicillin at home 0.2% [1/554] 10.8% (60/554)
RCT <59m vs vs Patel A,2015
vs
7 days oral amoxicillin for 48 hours at
hospital followed by 5 days at home 0.2% [1/564] 18.1% (102/564)
14
Clinical Question 3. WHAT DIAGNOSTIC AIDS ARE INITIALLY REQUESTED FOR A PATIENT
CLASSIFIED AS EITHER pCAP A or pCAP B BEING MANAGED IN AN AMBULATORY SETTING?
SUBCOMMITTEE MEMBER
Marion O. Sanchez
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT.*
1. Chest x-ray may be requested to rule out pneumonia-related complications or pulmonary conditions simulating pneumonia
[Recommendation Grade D].
1.1. It should not be routinely requested to predict end-of-treatment clinical outcome [Recommendation Grade A].
2. Chest x-ray, complete blood count, C-reactive protein, erythrocyte sedimentation rate, procalcitonin, or blood culture should not
be routinely requested to determine appropriateness of antibiotic usage [Recommendation Grade D].
SUMMARY OF EVIDENCE
Gap in knowledge. There are no published studies available for review.
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of current grading of recommendation.
15
Clinical Question 4. WHAT DIAGNOSTIC AIDS ARE INITIALLY REQUESTED FOR A PATIENT
CLASSIFIED AS EITHER pCAP C or pCAP D BEING MANAGED IN A HOSPITAL SETTING?
COMMITTEE MEMBER
Cristan Q. Cabanilla
BACKGROUND.
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. For pCAP C,
1.1. The following ancillary/diagnostic procedures should be done.
1.1.1. To assess gas exchange
1.1.1.1. Oxygen saturation using pulse oximetry [Recommendation Grade D]
1.1.1.2. Arterial blood gas [Recommendation Grade D]
1.1.2. To determine etiology
1.1.2.1. Gram stain and/or culture and sensitivity of pleural fluid when available [Recommendation Grade D]
1.2. The following ancillary/diagnostic procedures may be done
1.2.1. To confirm clinical suspicion of multilobar consolidation, lung abscess, pleural effusion, pneumothorax or pneumomediastinum
1.2.1.1. Chest x-ray PA-lateral [Recommendation Grade D]
1.2.2. To determine appropriateness of antibiotic usage
1.2.2.1. C-reactive protein (CRP) [Recommendation Grade A]
1.2.2.2. Procalcitonin (PCT) [Recommendation Grade B]
1.2.2.3. Chest x-ray PA-lateral [Recommendation Grade C]
1.2.2.4. White Blood Cell (WBC) count [Recommendation Grade D].
1.2.2.5. Gram stain of sputum or nasopharyngeal aspirate [Recommendation Grade D]
1.2.3. To determine etiology
1.2.3.1. Sputum culture and sensitivity [Recommendation Grade C]
1.2.3.2. Blood culture and sensitivity [Recommendation Grade C]
1.2.4. To predict clinical outcome
1.2.4.1. Chest x-ray PA-lateral [Recommendation Grade B]
1.2.4.2. Pulse oximetry [Recommendation Grade B]
1.2.5. To determine the presence of tuberculosis if clinically suspected
1.2.5.1. Mantoux test (PPD 5-TU) [Recommendation Grade D]
1.2.5.2. Sputum smear for acid-fast bacilli [Recommendation Grade D]
1.2.6. To determine metabolic derangement
1.2.6.1. Serum electrolytes [Recommendation Grade C]
1.2.6.2. Serum glucose [Recommendation Grade C]
2. For pCAP D, a referral to a specialist should be done [Recommendation Grade D]
16
Clinically important endpoint: determination of metabolic derangement for immediate correction on admission
1.13. pH in arterial blood gas for metabolic acidosis [Recommendation Grade C2]
1.14. Serum sodium for hyponatremia [Recommendation Grade B2]
1.15. Serum potassium for hypokalemia [Recommendation Grade C2]
Clinically important endpoint: predictor of clinical outcome
1.16. Predictive marker for mortality
1.16.1. pH in arterial blood gas for metabolic acidosis [Recommendation Grade B1]
1.17. Predictive marker for initial treatment failure
1.17.1. Pulse oximetry for oxygen saturation less than 90% at room air, chest x-ray PA-lateral for
pleural effusion or consolidation, or WBC for leukocytosis or leukopenia [Recommendation Grade B1]
1.17.2. Blood culture for bacteremia, serum hemoglobin for anemia, or serum glucose for
hypoglycemia [Recommendation Grade B2]
1.18. Predictive marker for prolonged hospitalization or pneumatocoele formation
1.18.1. Lung ultrasound showing impaired perfusion and hypoechoic lesions [Recommendation Grade B2]
2. For pCAP D, a referral to a specialist may be done for additional diagnostic tests [Recommendation Grade D]
3. For uncomplicated pCAP C, the following may not be requested.
Clinically important endpoint: determination of underlying microbial etiology
3.1. Blood culture [Recommendation Grade B2]
Clinically important endpoint: prediction of clinical outcome
3.2. CRP as marker for risk of treatment failure or prolonged hospitalization [Recommendation Grade B2].
SUMMARY OF EVIDENCE
1. Clinically important endpoint: surrogate markers for possible presence of pathogens requiring initial empiric
antibiotic with microbiology as the reference standard
DIAGNOSTIC AID : FINDINGS ODDS RATIO YIELD SPECIFICITY
PATHOGEN [95% CI] [%] p VALUE [95% CI] AUTHOR/YEAR
STUDY DESIGN
C-reactive protein [CRP] : >80 mg/L 3.6
Bacterial/atypical vs viral pathogen [1.65–8.07] 0.001 Elemraid M,2014
Prospective cohort
CRP : elevated 19
Pneumococcal vs viral pathogen [5-75] Galetto-Lacour A,2013
Prospective cohort
CRP : elevated
Bacterial vs viral pathogen 0.020 Hoshina T,2014
Retrospective cohort
CRP : > 200 ug/ml
Bacterial pathogen 56.10% Huang H,2014
Case control
CRP : abnormal 30.9%
Mycoplasma p vs non-Mycoplasma p vs 0.002 Gao J,2015
Cross-sectional 23.7%
Procalcitonin [PCT] : elevated 23
Bacterial vs non-bacterial pathogen [5-117] Galetto-Lacour A,2013
Prospective cohort
PCT : elevated
Pneumococcal vs non-bacterial pathogen 0.0008 Hoshina T,2014
Retrospective cohort
Lipocalin 2 : >130.1 ng/ml
Probable bacterial pathogen 85.7% Huang H,2014
Case control
Chest x-ray : pneumonia 93%
Pneumococcal infection Nascimento-Carvalho C,2015
[80-98]
Cross-sectional
IgM assay : 1.65 mean value 96.93%
Mycoplasma pneumoniae [reference std: Medjo B,2014
Cross-sectional RT-PCR]
White blood cell count [WBC] : abnormal 65.5%
Mycoplasma p vs non-Mycoplasma p vs 0.001 Gao J,2015
Cross-sectional 55.2%
WBC : abnormal Not
Bacterial vs non-bacterial pathogen significant Hoshina T,2014
Cohort
WBC : >15 × 109/L 0.5
Bacterial vs viral pathogen 0.320 Elemraid M,2014
[0.13–1.96]
Prospective cohort
17
Neutrophil count : >10 × 109 /L 5.9
Bacterial vs viral pathogen 0.012 Elemraid M,2014
[1.47–23.94]
Prospective cohort
Neutrophil count : abnormal Not
Bacterial vs non-bacterial pathogen significant Hoshina T,2014
Cohort
Neutrophil to lymphocyte ratio : 2.7
Bacterial vs viral pathogen <0.001
Retrospective cohort Bekdas M,2014
CRP to mean platelet volume ratio : 11.0
Bacterial vs viral pathogen <0.001
Retrospective cohort
2. Clinically important endpoint: radiologic evidence of clinical suspicion of necrotizing pneumonia, multilobar
consolidation, lung abscess, pleural effusion, pneumothorax or pneumomediastinum
CONDITION DIAGNOSTIC AID INCIDENCE AUTHOR / YEAR
Chest x-ray 32/882 [3.7%] Krenke K,2015
Necrotizing pneumonia Lung ultrasound 10/140 [7.1%]
Lai S,2015
Lung ultrasound + CT scan 70/96 [72.1%]
3. Clinically important endpoint: determination of underlying microbial etiology
The Task Force recognizes the trade-off between the need to identify microbial etiology and the cost-benefit
ratio in terms of actual yield. There are no local data available for review.
YIELD
SPECIMEN : FINDINGS REMARKS AUTHOR/YEAR
n/N [%, CI 95%]
TECHNIQUE / STUDY DESIGN
PATHOGEN CONTAMINANT
RESPIRATORY SECRETIONS
Induced sputum : +bacteria, Mycoplasma, virus 69/76 Honkinen M,2012
Culture, RT-PCR / Prospective cohort [91%]
Sputum : +bacteria 138/464 Vong S,2013
Culture / Prospective cohort [29.7%]
Nasopharyngeal aspirate : +Mycoplasma p 24/166 Medjo B,2014
RT-PCR / Cross-sectional [14.5%]
Nasopharyngeal aspirate : +Mycoplasma p 38/368 Gotoh K,2012
Loop-med isothermal amp ass / Cross-sectional [10.3%]
Nasopharyngeal aspirate : bacteria, virus 38/45 Chen Y,2012
Multiplex PCR,Quick Ag,culture / Cross-sectional [84.4%]
Lung aspirate and pleural fluid : bacterial 20/57 Howie S,2014
Culture / Cross-sectional [38%]
PLEURAL FLUID
Pleural fluid : +bacteria 79/288 Deceuninck G, 2013
Culture / Retrospective cohort [27.4%]
Pleural fluid : +bacteremia 2/5 Heine D,2013
Culture / Cross-sectional [40.0%]
BLOOD
Blood : +bacteremia CAP: severe vs Iroh Tam P,2015
Culture / Meta-analysis [5.14%,3.61-7.28%] [14.7%] less severe [p=.008]
Blood : +bacteremia 27/862 Vong S,2013
Culture / Prospective cohort [3.1%]
Blood : +bacteremia 18/405 22/405 Chisti M ,2014
Culture / Prospective cohort [4.4%] [5%]
Blood : +bacteremia 0/45 Chen Y,2012
Culture / Prospective cohort
Blood : +bacteremia 2/171 3/171 Lai E,2014
Culture / Prospective cohort [1.2%] [1.8%]
Blood : +bacteremia 2/139 3/139 Parikh K,2014
Culture / Retrospective cohort [1.4%] [2.1%]
Blood : +bacteremia 26/369 7/369 Myers A,2013
Culture / Retrospective cohort [7%, 4.7–10.1%] [1.8%]
Blood : +bacteremia 53/288 With empyema Deceuninck G,2013
Culture / Retrospective cohort [18.4%] thoracis
Blood : +bacteremia 6/390 9/390 McCulloh R,2015
Culture / Retrospective cohort [1.5%] [2.3%]
Blood : +bacteremia 5/155 1/155 Heine D,2013
Culture / Cross-sectional [3.2%] [<1% ]
Blood : +bacteremia 17/329 16/329 Real-time PCR Selva A,2013
Culture / Cross-sectional [5.1%] [4.9%] from dried blood spot
Blood : +bacteremia 2/82 Ybanez S,2014
Culture / Case control [2.4%]
Blood : +Pneumococcal bacteremia 1/73 Complicated pneumo-
Culture / Case control [1.4%] coccal CAP vs control Esposito S,2012
Blood : +Pneumococcal bacteremia 67/73 (p=0.02)
PCR for Streptococcus pneumoniae / Case control [91.8%]
18
4. Clinically important endpoint: number of cases with metabolic derangement
DIAGNOSTIC AID : FINDINGS
n/N [%] REMARKS AUTHOR/YEAR
STUDY DESIGN
Blood pH : metabolic acidosis [total serum CO2 <17 mMol/L] 66/164 Diarrhea as Chisti M,2012
Case control [40.2%] comorbid illness
Blood pH : metabolic acidosis [pH<7.0,HC03<24 mM, anion gap>16 mM] Total number of Wang L, 2013
Case control cases: 21
Serum sodium : soidum <130 mm/L Total number of Consolidation by Glatstein M,2014
Cross-sectional cases: 54 chest xray
Serum sodium : soidum <130 mm/L 104/312 Wrotek A,2013
Cross-sectional [33.3%]
Serum potassium : potassium <3.5 mMol/L 51/180 Diarrhea as Chisti M,2013
Prospective cohort [31%] comorbid illnes
19
Clinical Question 5. WHEN IS ANTIBIOTIC RECOMMENDED?
SUBCOMMITTEE MEMBERS
Cynthia Theresa M. Rimando
Ernesto Z. Salvador
BACKGROUND
nd
2012 2 PAPP UPDATE SUMMARY HIGHLIGHT*
1. For pCAP A or pCAP B, an antibiotic may be administered if a patient is
1.1. beyond 2 years of age [Recommendation Grade D]; or
1.2. with high grade fever without wheeze [Recommendation Grade D].
2. For pCAP C, an antibiotic
2.1. should be administered if alveolar consolidation on chest x-ray is present [Recommendation Grade C].
2.2. may be administered if a patient is with any of the following:
2.2.1. Elevated serum C-reactive protein [CRP] [Recommendation Grade A]
2.2.2. Elevated serum procalcitonin level [PCT] [Recommendation Grade B]
2.2.3. Elevated white cell count [WBC] [Recommendation Grade D].
2.2.4. High grade fever without wheeze [Recommendation Grade D].
2.2.5. Beyond 2 years of age [Recommendation Grade D].
3. For pCAP D, a specialist should be consulted [Recommendation Grade D].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation.
20
SUMMARY OF EVIDENCE
1. Clinically relevant information: epidemiology
1.1. Ambulatory patients
Gap in knowledge. No published data are available for review.
1.2. Hospitalized patients
1.2.1. Gap in knowledge in local literature. No local data are available for review.
1.2.2. Foreign data
POSITIVE YIELD [n] POSITIVE YIELD OF POSITIVE YIELD
COUNTRY PER SAMPLE PATHOGENS1 REQUIRING OF
LABORATORY METHOD AGE INITIAL ANTIBIOTIC VIRAL PATHOGEN AUTHOR
[or SUBJECT] [N] YEAR
n/N [%] THERAPY n/N [%]
n/N [%]
0-16y 806/3181 [25%] 2375/3181 [75%]
0-1y 716/1249 [57%] 1440/2375 [67%]
China 1381/3181 Wei L
Culture, molecular 1-4y 451/1249 [37%] 744/2375 [31%] 2015
4-6y 42/1249 [3%] 92/2375 [4%]
6-16y 40/1249 [3%] 99/237[4%]
Austria 190/279 [68%] Adolescent 83/190 [34%] 107/190 [56%] Kurz H
Culture, molecular Child 2013
China 1613/1613 [100%] Child 678/1613 [42%] 935/1613 [58%]2 Peng Y
Culture 2015
United States 1802/2222 [81%] <18y 330/1802 [18%] 1472/1802 [82%] Jain S
Culture, serology 2015
Niger 138/1691 [8%] <5y 126/138 [91%] Lagare A
102/138 [74%]
Molecular 2015
UK
Culture, molecular, Elemraid M
214/401 [53%] <16y 132/214 [62%] 82/214 [38%] 2013
urine ag test, serology,
immunofluorescence
Procalcitonin : elevated 23
Bacterial vs non-bacterial pathogen [5-117] Galetto-Lacour A
Prospective cohort 2013
21
Procalcitonin : elevated Hoshina T
Pneumococcal vs non-bacterial pathoge 0.0008
2014
Retrospective cohort
22
Clinical Question 6. WHAT EMPIRIC TREATMENT SHOULD BE ADMINISTERED IF A BACTERIAL
ETIOLOGY IS STRONGLY CONSIDERED?
SUBCOMMITTEE MEMBERS
Alfredo L. Bongo Jr
Lydia K. Chang
Edward A. Chua
Arnold Nicholas T. Lim
Doris Louise C. Obra
Nilyn Elise O. Ygnacio
Dahlia L. Yu
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. For a patient who has been classified as pCAP A or pCAP B without previous antibiotic,
1.1. amoxicillin [40-50 mg/kg/day, maximum dose of 1500 mg/day in 3 divided doses for at most 7 days] is the drug of choice
[Recommendation Grade B].
1.1.1. Amoxicillin may be given for a minimum of 3 days [Recommendation Grade A].
1.1.2. Amoxicillin may be given in 2 divided doses for a minimum of 5 days [Recommendation Grade B].
1.2. Azithromycin [10 mg/kg/day OD for 3 days, or 10 mg/kg/day at day 1 then 5 mg/kg/day for days 2 to 5, maximum dose of 500
mg/day], or clarithromycin [15 mg/kg/day, maximum dose of 1000 mg/day in 2 divided doses for 7 days] may be given to
those patients with known hypersensitivity to amoxicillin [Recommendation Grade D].
2. For a patient who has been classified as pCAP C, without previous antibiotic,
2.1. requiring hospitalization, and
2.1.1. has completed the primary immunization against Haemophilus influenzae type b, penicillin G [100,000 units/kg/day in 4
divided doses] administered as monotherapy is the drug of choice [Recommendation Grade B].
2.1.2. has not completed the primary immunization or immunization status unknown against Haemophilus influenzae type b,
ampicillin [100 mg/kg/day in 4 divided doses] administered as monotherapy is the drug of choice [Recommendation Grade B].
2.1.3. above15 years of age [Recommendation Grade D], a parenteral non-antipseudomonal β-lactam (β-lactam / β-lactamase
inhibitor combination (BLIC), cephalosporin or carbapenem] + extended macrolide [azithromycin or clarithromycin], or a
parenteral non-antipseudomonal β-lactam [β-lactam/ β-lactamase inhibitor combination (BLIC], cephalosporin or
carbapenem] + respiratory fluoroquinolones [levofloxacin or moxifloxacin] administered as combination therapy may be given
[Recommendation Grade A].
2.2. who can tolerate oral feeding and does not require oxygen support, amoxicillin [40-50 mg/kg/day, maximum dose of 1500
mg/day in 3 divided doses for at most 7 days] may be given on an outpatient basis [Recommendation Grade B].
3. For a patient classified as pCAP C who is severely malnourished or suspected to have methicillin-resistant Staphylococcus aureus, or
classified as pCAP D, referral to a specialist is highly recommended [Recommendation Grade D].
4. For a patient who has been established to have Mycobacterium tuberculosis infection or disease, antituberculous drugs should be
started [Recommendation Grade D].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation.
23
2.1.2. has not completed the primary immunization, or immunization status unknown, against
Haemophilus influenzae type b, ampicillin [100 mg/kg/day in 4 divided doses] may be given
[Recommendation Grade B2].
2.2. who can tolerate oral feeding and does not require oxygen support, amoxicillin [40-50 mg/kg/day in
areas of proven low amoxicillin resistance and 90 mk/kg/day maximum dose of 1500 mg/day in 3
divided doses for at most 7 days in areas of proven high amoxicillin resistance] may be given on an
outpatient basis [Recommendation Grade B2].
3. For a patient who has been classified as pCAP D, a specialist may be consulted [Recommendation Grade D].
4. For a patient suspected to have community-acquired methicillin-resistant Staphylococcus aureus,
4.1. vancomycin may be started [Recommendation Grade D].
4.2. a specialist may be consulted [Recommendation Grade D].
5. Ancillary treatment as provided in Clinical Question 11 may be given [Recommendation Grade D].
SUMMARY OF EVIDENCE
1. Decision guides in what empiric treatment should be started for pCAP A, B and C
1.1. Epidemiology of antibiotic-requiring pathogen in the general pediatric population
COUNTRY LAB Streptococcus OTHER BACTERIA ATYPICAL ORGANISM
METHOD AGE +YIELD pneumoniae % [95% AUTHOR
%
STUDY DESIGN % % [95% CI] YEAR
[95% CI]
CI]
Latin America Haemophilus influenzae: 3.64% [1.62–6.42] Mycoplasma pneumoniae
3.56% [0.99–7.64]
and Staphylococcus aureus: 3.44% [2.08–5.11] Chlamydia trachomatis
<5y 30.6% 11.08% Gentile A
Carribean
[7.63 -15.08] 2.97% [0.74–6.60] 2012
Culture, PCR Haemophilus influenzae b:3.08%[1.21–5.79]
Meta-analysis Streptococcus pyogenes: 1.54%[0.49–3.15] Chlamydia pneumoniae
2.60% [0.22–7.46]
Haemophilus influenzae: 38.0%
Klebsiella pneumoniae: 14.3%
Cambodia Pseudomonas aeruginosa:12.3% Vong S
Culture >5y 89.0% 17.7% Not determined 2015
Bordetella pseudomallei: 9.3%
Cross-sectional
Staphylococcus aureus: 3.7%
Mycobacterium sp: 15.7%
China Hemophilus influenzae: 40.8% Mycoplasma pneumoniae Peng Y
Culture Child 50.2% 29.7% 2015
Moraxella catarrhalis: 7.3% 29.82%
Cross-sectional
Finland Hemophilus Influenzae: 38.0%
6m-15y 91% 50% Mycoplasma pneumoniae Honkinen M
Culture Moraxelle catarrhalis: 28.0%
3.0% 2012
Cross-sectional Staphylococcus aureus: 13.0%
24
1.2.3. Staphylococcus aureus
2012 2013 2014 2015
Penicillin 95.4% 95.0% 95.5% 96.0%
Oxacillin 54.9% 53.0% 60.3% 62.6%
Vancomycin 0% 1.0% 0.9% 0.7%
Clindamycin 8.4% 12.0% 11.0% 10.4%
Erythromycin 10.9% 15.0% 12.0% 11.0%
Rifampin - 1.0% 4.1% 4.9%
Ciprofloxacin - 8.0% 7.4% 4.9%
Cotrimoxazole 9.3% 14.0% 22.0% 25.9%
Linezolid 1.6% 2.0% 1.2% 1.7%
1.2.4. Methicillin-resistant Staphylococcus aureus
2012 2013 2014 2015
Rifampin 7.7% 4.0% 6.0% 6.9%
Vancomycin 0% 1.0% 1.0% 0.9%
Clindamycin 13.4% 12.0% 14.% 14.0%
Erythromycin - 15.0% 16.% 14.0%
Ciprofloxacin 7.5% 7.0% 10.% 6.2%
Cotrimoxazole 14.7% 18.0% 26.% 29.0%
Linezolid 3.5% 1.0% 1.7% 2.2%
1.3. Clinical trials with clinical treatment failure, cure rate, relapse rate, adverse event, side effect
readmission, ICU admission and clinical course as clinically important endpoints.
RESULTS
NUMBER CLINICALLY AUTHOR
STUDY DESIGN RISK or ODDS RATIO YEAR
INTERVENTION OF IMPORTANT p VALUE REMARKS
AGE [95% CI]
SUBJECTS ENDPOINT
Risk classification scheme: pCAP A or B
233 vs 133 Cure rate 1.22 [0.50-2.94]
Azithromycin
236 vs 156 Failure rate 0.73 [0.18-2.89]
vs erythromycin
84 vs 69 Side effects 0.92 [0.18-4.73]
124 vs 110 Cure rate 1.61 [0.86-3.08]
Clarithromycin 124 vs 110 Failure rate 0.52 [0.12-2.23]
vs erythromycin 121 vs 105 Relapse rate 0.17 [0.02-1.45]
133 vs 127 Adverse event 1.07 [0.60-1,90]
125 vs 63 Cure rate 1.02 [0.54-1.95]
Azithromycin
vs co-amoxiclav 164 vs 112 Failure rate 1.21 [0.42-2.53]
164 vs 112 Side effect 0.15 [0.04-0.61]
50 vs 50 Cure rate 10.44 [2.85-38.21]
50 vs 50 Side effect 5.21 [0.24-111.24]
Co-amoxiclav 948 vs 839 Failure rate 1.18 [0.91-1.51] Lodha R
Subgroup in vs amoxicillin nonsevere CAP 2013
meta-analysis 203 vs 99 Failure rate 1.71 [0.94-3.11]
<18y severe CAP
Amoxicillin 42 vs 42 Cure rate 2.05 [0.18-23.51]
vs cefuroxime
Amoxicillin 923 vs 142 Failure rate 0.64 [0.41-1]
vs chloramphenicol
Cotrimoxazole 55 vs 56 Cure rate 1.06 [0.47-2.40]
vs chloramphenicol
Amoxicillin 42 vs 40 Cure rate 1.05 [0.06-17.40]
vs clarithomycin
Cefuroxime 42 vs 40 Cure rate 0.51 [0.04-5.89]
vs clarithromycin
Cohort B-lactam monotherapy 1164 Treatment Not Ambroggio
1-18y vs macrolide failure significant L 2015
25
Risk classification scheme: pCAP C
Amoxicillin 68 vs 86 Failure rate 0.75 [0.17-3.25]
vs procaine penicillin
Cotrimozaxole 349 vs 374 Cure rate 1.58 [0.26-9.69]
vs procaine penicillin 303 vs 311 Failure rate 1.72 [0.41-7.27]
Cotrimozaxole 66 vs 68 Cure rate 1.15 [0.36-3.61]
vs penicillin+ampicillin
Chloramphenicol 559 vs 557 Adverse events 1.26 [0.96-1.66]
vs penicillin+gentamycin 559 vs 557 Readmission < d 30 1.61 [1.02-2.55]
Chloramphenicol+ampicillin 479 vs 47 Failure rate day 5 1.51 [1.04-2.19]
vs gentamycin
Subgroup Lodha R
Chloramphenicol+penicillin 46 vs 51 Cure rate 1.36 [0.47-3.93]
in meta- vs ceftriaxone 2013
analysis
<18y Ampicillin 52 vs 49 Cure rate 0.48 [0.15-15.1]
vs penicillin+chloramphenicol
Benzathine penicillin 135 vs 146 Cure rate 0.43 [0.27-1.01]
vs procaine penicillin
Penicillin+gentamycin 38 vs 33 Failure rate 0.86 [0.05-14.39]
vs co-amoxiclav 55 vs 56 Relapse rate 1.02 [0.24-4.30]
Co-amoxiclav 8/56 vs 7.48 Failure rate 0.98 [0.93-2.92]
vs oxacillin+ceftriaxone
1982 vs 1960 Failure rate day 3 0.95 [0.78-1.15]
Oral vs parenteral antibiotic
for severe pneumonia 1948 vs 1922 Failure rate <5y 0.91 [0.76-1.09]
1048 vs 1028 Relapse rate 1.28 [0.34-4.82]
Cohort Broad vs narrow 236 vs 256 Readmission within 0.25 Queen M
2m-18y spectrum antiobiotic 7 days 2014
Cohort Broad vs narrow 13954 vs ICU admission 0.85 [0.27 -2.73] Wlliams D
<5y spectrum antibiotic 1610 2013
RCT Ampicillin or penicillin 66 vs 253 Treatment failure 7.6% Dinur-Schejter Y
3m-2y vs cefuroxime vs 4.7% 2013
Treatment failure 0.82 [0.55-0.82]
Meta- nd
2 day
analysis Amoxicillin 12364 Das R
3-59 m vs standard IV antibiotic subjects Treatment failure 0.92 [0.76-1.10] 2013
6th day
Meta- Amoxicillin
analysis Lodha R
vs procaine penicillin 68 vs 86 Failure rate 0.75 [0.17-3.25]
<18y 2013
Cohort Penicillin G q 4 vs q6 120 vs 144 Final outcome No diffe- Brandao A
2m-11y ference 2014
RCT Amoxicillin given at home 68 vs 86 Treatment failure HR < 0.01 Patel A
3-59m then hosp vs at hosp alone 1.79 [1.30-2.46] 2015
0.71
Transfer to ICU [Age:1-4y]
> 2nd day 0.14
[Age:5–17y]
0.30
[Age:1-4y]
Mortality
0.58
Cohort Ceftriaxone 4701 vs 8892 [Age:5–17y] Leyenaar J
1-17y vs ceftriaxone+macrolide 0.10 [Age: 2014
All-cause 1-4y]
readmission
<30 days 0.58
[Age:5–17y]
Pneumonia-related 0.96
[Age:1-4y]
readmission <30 days
0.37
[Age:5–17y
Cohort Β-lactam+macrolide 2489 vs Readmission 0.69 (0.41-1.12) Ambroggio L
1-18y vs B-lactam monotherapy 18254 2013
RCT Penicillin G Not Amarilyo G
3m–15y vs IV cefuroxime 58 children Clinical course significant 2014
7.7%
RCT Amoxicillin vs Agwayu A
<2y vs benzyl penicillin Treatment failure 8.0% 2015
[perprotocol
analysis]
26
Clinical Question 7. WHAT TREATMENT SHOULD BE INITIALLY GIVEN IF A VIRAL ETIOLOGY IS
STRONGLY CONSIDERED?
SUBCOMMITTEE MEMBERS
Vivian A. Ancheta
Janet C. Bernardo
Janet Myla Q. Bonleon
Julie Iris C. Clapano
Yadnee V. Estrera
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. Oseltamivir (30 mg twice a day for ≤15 kg body weight, 45 mg twice a day for >15-23 kg, 60 mg twice a day for >23-40 kg, and 75 mg
twice a day for >40 kg) remains to be the drug of choice for laboratory confirmed [Recommendation Grade A], or clinically suspected
[Recommendation Grade D] cases of influenza.
2. The use of immunomodulators for the treatment of viral pneumonia is not recommended [Recommendation Grade D].
3. Ancillary treatment as provided in Clinical Question 11 may be given [Recommendation Grade D].
27
SUMMARY OF EVIDENCE
1. Epidemiology
1.1. Local data
1.1.1. Rate of viral pneumonia [ICD code J12.9, J12, J12.0, J12.2, J12.8] relative to all discharges from January
2012 to December 2015 as reported by hospitals accredited by Philippine Pediatric Society : 0.11%.
[ICD 10 Registry, Committee on Registry of Childhood Disease, Philippine Pediatric Society].
1.1.2. Local epidemiology among hosptalized viral CAP
RATE AUTHOR
SITE VIRAL ISOLATE % YEAR
<1y old 1-4y old >5y old
Total 28.1% [106/377]
Cordillera RSV 60.3% 26.4% 0.94% Perez C
Administrative Flu B 1.9% 2.8% 0.94% 2012
Region Flu A 0.94% 2.8% 0
Flu A [H1N1] 1.9% 0 0
Total 61.2% [501/819]
Rhinovirus 30.5% Suzuki A
Tacloban RSV 24.1% 2012
Adenovirus 4.0%
Flu A 2.2%
2. Influenza-like illness.
2.1. Burden of pneumonia during influenza pandemic.
0.59 [0.55-0.62] excess pneumonia visits per 1,000 US population [Self W,2014]
2.2 Clinical trials on neuraminidase inhibitor.
INTERVENTION SUBGROUP ODDS or RISK RATIO MEAN DIFFERENCE AUTHOR
ENDPOINT
STUDY DESIGN ANALYSIS [95% CI] [95% CI] YEAR
3 studies Risk for pneumonia 1.06 [0.62-1.83]
Oseltamivir
1 study Time to first symptom relief -29.40 [-47.04-11.76]
versus placebo
Meta-analysis 2 studies Serious adverse event 1.97 [0.59-6.56 ]
2 studies Vomiting 1.70 [1.23-2.35 ] Jefferson T
Zanamivir 2 studies Risk for pneumonia 0.53 [0.12-2.38] 2014
versus placebo 2 studies Time to first symptom relief -1.08 [-2.32-0.15]
Meta-analysis 2 studies Adverse event: nausea and vomiting 0.54 [0.24-1.22]
2.3. Treatment regimen [American Academy of Pediatrics, Committee on Infectious Diseases, 2015; Kimberlin D,2013]
2.3.1. oseltamivir [for infants 3-8 months old at 3 mg/kg per dose twice daily x 5 days, for infants 9-11 months
old at 3.5 mg/kg per dose twice daily x 5 days, for >12 months old: body weight <15kg at 30 mg twice daily x
5 days, >15-23kg at 45 mg twice daily x 5 days, >23-40kg at 60 mg twice daily x 5 days, >40kg at 75 mg
twice daily x 5 days; doses to be started within 48 hours of onset of influenza-like symptoms.
2.3.2. zanamivir [for children >7 years old at 10mg (two 5-mg inhalations) twice daily x 5 days, within 36
hours of onset of influenza-like symptoms.
28
Clinical Question 8. WHEN CAN A PATIENT BE CONSIDERED AS RESPONDING TO CURRENT
THERAPEUTIC MANAGEMENT?
SUBCOMMITTEE MEMBER
Beatriz Praxedez Apolla I. Mandanas
BACKGROUND.
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. Decrease in respiratory signs and/or defervescense within 72 hours after initiation of antibiotic are predictors of favorable response
[Recommendation Grade D].
2. If clinically responding, further diagnostic aids to assess response such as chest x-ray, C-reactive protein and complete blood count
should not be routinely requested [Recommendation Grade D].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation.
29
SUMMARY OF EVIDENCE
1. Clinical stability
For purpose of standardization, the Task Force has defined the following:
1.1. Absolute clinical stability as resolution of ALL pneumonia-associated signs and symptoms AND
recovery of pre-pneumonia health status.
1.2. Approaching clinical stability as resolution of ANY pneumonia-associated sign or symptom OR
delayed recovery of pre-pneumonia health status.
1.3. Time to clinical stability as period in hours from the time an intervention has started up to complete
resolution of any pneumonia-associated sign or symptom.
TIME TO RESOLUTION
STUDY DESIGN N STABILITY N AUTHOR
Median (IQR) in hours, CI 95%]
PHYSIOLOGIC ENDPOINT DEFINITION YEAR
AGE
<2y 2-4y 5-17 <2y 2-4y 5-17
Cohort
130 90 101
Single endpoint
1. Fever Temp: 36.0-37.9 101 61 63 14.5 (4.5-45.3) 18.4 (2.8-42.8) 10.6 (0.8-34)
2. Tachycardia 1 21 73 62 4.5 (0.3-18.4) 21.8 (5.7,-1.9) 18 (5.8-42.2)
Normal
3. Tachypnea 97 63 62 38.6 (18.7-68.9) 31.6 (9.5-61.9) 24.3 (10.8-59.2)
4; Needing O2 support None 90 58 61 39.5 (19.2-73.6) 44.2 (24-77.6) 38.3 (18-70.6) Wolf R
334 2015
Multiple endpoints
1. Tachypnea Normal RR 108 72 69 40.5 (20.1-75.0) 39.6 (15.6-79.2) 30.4 (14.7-59.2)
+ needing O2 support None
2. Tachypnea + tachycardia Normal RR,HR 109 73 68 40.2 (19.5-73.9) 35.9 (15.9-77.6) 29.8 (17.2-56.6)
+ needing O2 support None
3. Tachypnea + fever Normal RR, none 110 77 73 40.5 (20.7-70.1) 39.1 (18.4-77.6) 28.2 (14.7-44.7)
+ needing O2 support None
4.Tachypnea + tachycardia Normal RR,HR 110 72 71 40.5 (20.7-70.1) 39.7 (20.1-77.5) 29.2 (18.2-54)
+ fever + needing O2 support None
1
Based on American Heart Association. 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and
emergency cardiovascular care (ECC) of pediatric and neonatal patients: pediatric basic life support. Pediatrics 2006; 117:e989–1004.
30
Clinical Question 9. WHAT SHOULD BE DONE IF A PATIENT IS NOT RESPONDING TO CURRENT
THERAPEUTIC INTERVENTION?
COMMITTEE MEMBERS
Catherine S. Palaypayon
Raymund Anthony L. Manuel
BACKGROUND
nd
2012 2 PAPP UPDATE SUMMARY HIGHLIGHT*
1. If a patient classified as either pCAP A or pCAP B is not responding to the current antibiotic within 72 hours, consider any of the
following [Recommendation Grade D]:
1.1. Other diagnosis
1.1.1. Coexisting illness
1.1.2. Conditions simulating pneumonia
1.2. Other etiologic agents for which CRP, chest x-ray or CBC may be used to determine the nature of the pathogen
1.2.1. May add an oral macrolide if atypical organism is highly considered
1.2.2. May change to another antibiotic if microbial resistance is highly considered
2. If an in-patient classified as pCAP C is not responding to the current antibiotic within 72 hours, consider any of the ff [Recommendation Grade D].
2.1. Other diagnosis
2.1.1. Coexisting illness.
2.1.2. Conditions simulating pneumonia
2.2. Consider other etiologic agents for which CRP, chest x-ray or CBC may be used to determine the nature of the pathogen
2.2.1. May add an oral macrolide if atypical organism is highly considered
2.2.2. May change to another antibiotic if microbial resistance is highly considered
2.3. May refer to a specialist
3. If an in-patient classified as pCAP D is not responding to the current antibiotic within 72 hours, immediate consultation with a
specialist should be done [Recommendation Grade D]
*CQ 9 has been changed in the current guideline. Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and
Management of Pediatric Community-acquired Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation.
31
SUMMARY OF EVIDENCE
1. Description of failure of standard treatment at 48 hours after admission
COUNTRY n/N
DESCRIPTION OF TREATMENT FAILURE AUTHOR
STUDY DESIGN RATE
AGE GROUP [95% CI] YEAR
pCAP C [or SEVERE PNEUMONIA]
1. Development of signs of very severe pneumonia at any time, or 3/169
2. Absence of improvement of ALL of the following: indrawing (persistence), measured temperature 1.8% Agweyu A
reduction of ≥0.5 °C and respiratory rate (reduction of ≥5 bpm), or [0.4–5.1] 2014
Kenya 3. Identification of pathogen with in vitro resistance to antibiotics at any time point
Cohort 1. Worsening, compared to admission findings, of one or more of these clinical abnomalities: conscious
2-59m level, SaO2 <90%; RR (must have increased by at least 5 breaths/min), or temp (if initially<37.5°C, 42/453 Webb C
12% 2012
must have increased to >37.5°C); or
2. No improvement in any these clinical abnormalities; or
3. New findings of empyema, bacterial meningitis, shock or renal impairment (creatinine >100 mmol/L)
Nepal Failure to improve1 AND 1. a requirement for a change in antibiotics to second line therapy; or 209/610 Basnet S
Cohort 2. development of empyema or pneumothorax requiring surgical intervention; or 35% 2015
2-35m 3. admission to the intensive care unit for ventilator and/or inotropic support.
pCAP D [or VERY SEVERE PNEUMONIA]
1. Observed deteriorating level of consciousness or development of respiratory failure resulting in the
need for ICU transfer at any time point; or
2. Chest X-ray findings of lung abscess, bullae formation or PTB at any time point; or 43/201 Agweyu A
3. Absence of improvement of ALL of the following: indrawing (persistence), measured temperature re- 21.4% 2014
duction of ≥0.5°C, RR (reduction of ≥5 bpm), ability to drink AND requirement of supplementary O2; or [15.9–27]
Kenya 4. Identification of a pathogen on blood culture or from pleural fluid with in vitro resistance to antibiotics
Cohort at any time point.
2-59m 1. Worsening, compared to admission findings, of one or more of these clinical abnormalities: conscious
level, SaO <90%; respiratory rate (must have increased by at least 5 breaths/min), or temp (if
2
initially <37.5°C, must have increased to >37.5°C); or 69/165 Webb C
2. No improvement in any these clinical abnormalities; or 32% 2012
3. New findings of empyema, bacterial meningitis, signs of shock or renal impairment
(creatinine >100 mmol/L)
pCAP C [or SEVERE PNEUMONIA] and pCAP D [or VERY SEVERE PNEUMONIA]
1. No improvement or worsening of tachypnea or lower chest indrawing; or
India 2. New appearance, no improvement or worsening of danger signs such as inability to drink, abnormal 37/181 Jain D
Case control sleepiness, difficult to awake from sleep, stridor in a calm child, central cyanosis, and convulsions; or 20.4% 2013
3-59m 3. Occurrence of empyema, pneumothorax, lung abscess, meningitis, septicaemia, shock, respiratory
failure)
1
Persistence of lower chest indrawing or of any danger signs initially present despite 48 hours of treatment or appearance of new danger signs or
hypoxia with deterioration of a patient’s clinical status any time after initiation of treatment
2. Conditions associated with treatment failure for severe and nonsevere pneumonia
CONDITIONS ASSOCIATED WITH TREATMENT FAILURE AUTHOR
n/N [RATE]
AT LEAST 48 HOURS AFTER ADMISSION YEAR
Clinician’s decision to change treatment in absence of criteria 54/100 (54.0%)
Persistence of tachypnea, fever and indrawing 25/100 (25.0%)
Documented signs of deteriorating clinical status 12/100 (12.0%) Agweyu A
2014
Radiological findings informing change of treatment 2/100 (2.0%)
Bacteriological findings informing change of treatment 1/100 (1.0%)
Persistence of tachypnea or lower chest indrawing 10/31 (32.2%)
Empyema / pneumothorax 6/31 (19.3%)
Hypoxemia [SaO2 <90%] 7/31 (22.5%) Jain D
Persistence or new appearance of danger signs 5/31 (16.1%) 2013
Meningitis 2/31 (6.4%)
Lung abscess 1/31 (3.2%)
48 hr after admission 5 days after admission
Worsening conscious level 4 ( 3.6%) 3 ( 5.0%)
Worsening SaO2 19 (17.0%) 2 ( 3.0%)
Persistent SaO2 <90% 0 19 (31.0%)
Worsening respiratory rate 61 (55.0%) 12 (19.0%)
Webb C
Worsening temperature 22 (20.0%) 1 ( 2.0%)
2012
Persistent lower chest wall indrawing 0 31 (50.0%)
New bacterial meningitis 2 ( 1.8%) 2 ( 3.0%)
New renal impairment 0 1 ( 2.0%)
New signs of shock 3 ( 2.7%) 4 ( 6.0%)
New empyema 0 0
Admission to the intensive care unit 7/209 (3.34%)
OR [95% CI] 1
p VALUE Basnet S
Nasopharyngeal aspirate positive for human metapneumovirus 2.34 (0.62- 8.81) 0.209 2015
Nasopharyngeal aspirate positive for RSV 1.47 (0.91, 2.38) 0.115
1
Odds to having treatment failure
32
Clinical Question 10. WHEN CAN SWITCH THERAPY IN BACTERIAL PNEUMONIA BE STARTED?
COMMITTEE MEMBERS
Jean Marie E. Jamero
Beverly D. de la Cruz
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT *
1. For pCAP C,
1.1. switch from intravenous antibiotic administration to oral form 3 days after initiation of current antibiotic is recommended in a
patient who should fulfill all of the following [Recommendation Grade D]:
1.1.1. Responsive to current antibiotic therapy as defined in Clinical Question 8
1.1.2. Tolerance to feeding, and without vomiting or diarrhea
1.1.3. Without any current pulmonary (effusion / empyema; abscess; air leak, lobar consolidation, necrotizing pneumonia)
or extrapulmonary complications; and
1.1.4. Without oxygen support
1.2. switch therapy from three [3] days of parenteral ampicillin to
1.2.1. amoxicillin [40-50 mg/kg/day for 4 days] [Recommendation Grade B].
2. For pCAP D, referal to a specialist should be considered [Recommendation Grade D].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation.
SUMMARY OF EVIDENCE.
RESULTS
CAP SEVERITY
p AUTHOR
STUDY DESIGN Control group Switch therapy group
CLINICALLY IMPORTANT ENDPOINT VALUE YEAR
AGE GROUP
n=31 n=26
Mortality 0 0 -
Severe CAP RCT, Complications 0 0 - In-iw S
non-inferiority 2015
1-60m Readmission within 30 days 6.5% 3.8% 0.66
Length of stay 4.77+1.5 days 3.8+1.6 days 0.019
33
Clinical Question 11. WHAT ANCILLARY TREATMENT CAN BE GIVEN?
COMMITTEE MEMBER
Grace V. Malayan
BACKGROUND
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. For pCAP A or pCAP B,
1.1. cough preparation [Recommendation Grade A], elemental zinc [Recommendation Grade B], vitamin A [Recommendation Grade D],
vitamin D [Recommendation Grade D], probiotic [Recommendation Grade D] and chest physiotherapy [Recommendation
Grade D] should not be routinely given during the course of illness.
1.2. a bronchodilator may be administered in the presence of wheezing [Recommendation Grade D].
2. For pCAP C,
2.1. oxygen and hydration should be administered whenever applicable [Recommendation Grade D].
2.1.1. Oxygen delivery through nasal catheter is as effective as using nasal prong [Recommendation Grade A].
2.2. a bronchodilator may be administered only in the presence of wheezing [Recommendation Grade D].
2.2.2. Steroid may be added to a bronchodilator [Recommendation Grade B].
2.3. a probiotic may be administered [Recommendation Grade B].
2.4. cough preparation, elemental zinc, vitamin A, vitamin D and chest physiotherapy should not be routinely given during the
course of illness [Recommendation Grade A].
3. For pCAP D, referral to a specialist should be considered [Recommendation Grade D].
*Grading of recommendation in the 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community-acquired
Pneumonia was based on Sacket DL, Straus SE: Evidence Based Medicine 2000.
**Please see Methodology for description of grading of recommendation
34
SUMMARY OF EVIDENCE
Interventions of potential benefit in pCAP C to reduce length of hospital stay and improve crackles score.
Steroid 0.019 Justina M
RCT, double-blind, placebo-controlled 2012
Length of stay
Spirulina 0.0006 Dioniso-Delfin T
RCT, open label 2012
Zinc Crackles score 0.034 Guinto, M
RCT 2014
Interventions in pCAP A or B.
Cough preparation Not improved 0.80 [0.38-1.67] Combined child Chang CC
Meta-analysis and adult 2014
Steroid 2.38 [1.03-5.52] 0.04 [-] asthma hx Ambroggio L
Retrospective cohort Treatment failure 2014
1.12 [0.43-2.92] 0.80 [+] asthma hx
Interventions in pCAP C.
Steroid Risk of readmission Justina M
RCT, double-blind, placebo-controlled 0.46 2012
Chest physiotherapy Chaves G
Meta-analysis 0.11-0.79 2013
Vitamin D Das R
Meta-analysis 0.29
Length of stay 2013
Pooled mean Bernabe J
Zinc diff: -5.75 2012
Meta-analysis [-11.54-0.04]
0.88 Macalino M
[0.71-1.10] 2013
1.3 Wadha N
[0.8-2.1] 2013
Treatment failure Sempe rtegu F
1.00 2012
[0.68-1.50]
Shah G
0.423 2012
Zinc
Time to normalization of RR, 0.306 Srinivasan M
RCT, double-blind, placebo-controlled temperature 0.897 2012
and SaO2 0.823
0.05 Rulloda M
2012
Length of stay 0.193 Shah GS
2012
0.089 Low Fataki M
enrollment 2014
O2 delivery:bubble CPAP vs high flow O2 Treatment failure 0.50 Trial stopped Chisti M
RCT, open label [0.11-2.99] earlier 2015
Virgin coconut oil 0.336 Vierneza M
RCT 2012
Probiotic Mean: Becina P
RCT 3.2d vs 3.3d 2014
Oral folate Mean: Villanueva J
RCT, placebo-controlled Length of stay 4.0d vs 4.8d 2013
Vitamin D3 Not Mondragon A
RCT significant 2014
Nebulization: acetylcysteine vs saline Mean: Martinez M
RCT 2.5d vs 2.9d 2012
Nebulization: saline or bronchodilator Not Delizo M
Cross-sectional significant 2014
35
Clinical Question 12. HOW CAN PNEUMONIA BE PREVENTED?
COMMITTEE MEMBERS
Amelia G. Cunanan
Ma. Lucia P. Yanga
BACKGROUND.
2012 2nd PAPP UPDATE SUMMARY HIGHLIGHT*
1. The following should be given to prevent pneumonia.
1.1. Vaccine against 1.1.1. Streptococcus pneumoniae (conjugate type) [Recommendation Grade A]
1.1.2. Influenza [Recommendation Grade A]
1.1.3. Diphtheria, Pertussis, Rubeola, Varicella, Haemophilus Influenzae type b [Recommendation Grade A]
1.2 Micronutrient. 1.2.1. Elemental zinc for ages 2 to 59 months to be given for 4 to 6 months [Recommendation Grade A]
2. The following may be given to prevent pneumonia.
2.1 Micronutrient 2.1.1. Vitamin D3 supplementation [Recommendation Grade B]
3. The following should not be given to prevent pneumonia:
3.1 Micronutrient 3.1.1. Vitamin A [Recommendation Grade A]
SUMMARY OF EVIDENCE
1. Rationale for prevention: burden of illness
BURDEN SITE STUDY AGE AVERAGE NUMBER MEAN RATE SOURCE
PERIOD GROUP PER YEAR
MORBIDITY
Acute lower respiratory <5y 286 073 Department
2012-14 of Health
1
MORTALITY
Pneumonia-related. Philippine
Nationwide 4 Pediatric
ICD code 10 J18.0,18.9, 18.91, 2.26% Society,Inc3
18.92,18.93
Pneumonia-related Worldwide 2000-13 <5y 0.935 [UR5 0.817-1.057] 14.9% [UR5 13.0-16.8] Liu L,2014
6
ECONOMIC BURDEN
AGE 7
PNEUMONIA SEVERITY STUDY PERIOD GROUP ESTIMATED TOTAL HEALTH CARE COST
36
2. Interventions that may be beneficial to prevent pneumonia, or reduce pneumonia-related morbidity
and mortality
CLINICALLY RESULTS
INTERVENTION COUNTRY AUTHOR
IMPORTANT RISK, HAZARD or ODDS
STUDY DESIGN AGE REMARKS YEAR
ENDPOINT RATIO [95% CI]
Intervention of proven benefit: vaccination
CAP 43.2% vs 39.2%, p=0.005 Moore M
2015
USA
<18y All-cause CAP hosp 17-21% reduction in <5y Simonsen L
Empyema 37-50% reduction in <18y 2014
PCV 13 Uruguay CAP All-cause 78.1% reduction Pirez M
Time-trend analysis 2013
<14y hosp Pneumoccous 92.4% reduction
Argentina Radiologic CAP 20.1 [13.1-26.4], p<0.001 Gentile A
<5y 2015
hospitalization
Alaska Pneumococcal CAP 57% reduction Bruce M
<5y hospitalization 2015
3. Interventions requiring more studies to assess benefit in reducing the clinical impact of pneumonia
Vit D Acute lower respiratory [+] association between
Meta-analysis Children Vit D deficiency and Larkin A
infection [ALRI] severity 2014
[13 studies] increasing severity of ALRI
Zinc Fu W
Preschool Pneumonia-related 0.52 [0.11-2.39] 2013
Meta-analysis
[3 studies] children mortality
37
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12 Elemraid M, Rushton S, Thomas M, Spencer D, Gennery A, Clark J.: Utility of inflammatory markers in predicting the aetiology of
pneumonia in children Diagn Microbiol Infect Dis. 2014;79:458-62.doi:10.1016/j.diagmicrobio.2014.04.006.
13 Galetto-Lacour A, Alcoba G, Posfay-Barbe KM, Cevey-Macherel M, Gehri M, Ochs M, Brookes R, Siegrist C, Gervaix A.: Elevated
inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-
acquired pneumonia in children. Pediatr Infect Dis J 2013;32:1175-9.doi:10.1097/INF.0b013e31829ba62a.
14 Hoshina T, Nanishi E, Kanno S, Nishio H, Kusuhara K, Hara T.: The utility of biomarkers in differentiating bacterial from non-bacterial
lower respiratory tract infection in hospitalized children: difference of the diagnostic performance between acute pneumonia and
bronchitis. J Infect Chemother 2014;20:616-20. doi:10.1016/j.jiac.2014.06.003.
15 Gao J, Yue B, Li H, Chen R, Wu C, Xiao M.: Epidemiology and clinical features of segmental/lobar pattern Mycoplasma pneumoniae
pneumonia: A ten-year retrospective clinical study. Exp Ther Med 2015;10:2337-2344.
16 Nascimento-Carvalho C, Araújo-Neto C, Ruuskanen O.: Association between bacterial infection and radiologically confirmed pneumonia
among children. Pediatr Infect Dis J 2015;34:490-3.doi:10.1097/INF.0000000000000622.
17 Bekdas M, Goksugur S, Sarac E, Erkocoglu M, Demircioglu F.: Neutrophil/lymphocyte and C-reactive protein/mean platelet volume ratios
in differentiating between viral and bacterial pneumonias and diagnosing early complications in children. Saudi Med J 2014;35:442-7.
Clinical Question 6. What empiric treatment should be administered if a bacterial etiology is strongly considered?
1 Gentile A, Bardach A, Ciapponi A, Garcia-Marti S, Aruj P, Glujovsky D, Calcagno J, Mazzoni A, Colindres R.: Epidemiology ofcommunity-
acquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis. Int J Infect Dis 2012;16:e5-
15. doi:10.1016/j.ijid.2011.09.013.
2 Vong S, Guillard B, Borand L, Rammaert B, Goyet S, Te V, Try P, Hem S, Rith S, Ly S, Cavailler C, Mayaud C, Buchy P.: Acute lower
respiratory infections in ≥5 year-old hospitalized patients in Cambodia, a low-income tropical country: clinical characteristics and
pathogenic etiology. BMC Infectious Diseases 2013 13:97.
3 Peng Y, Shu C, Fu Z, Li QB, Liu Z, Yan L.:Pathogen detection of 1 613 cases of hospitalized children with community acquired pneumonia.
Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:1193-9.
4 Honkinen M, Lahti E, Österback R, Ruuskanen O, Waris M.Viruses and bacteria in sputum samples of children with community-acquired
pneumonia. Clin Microbiol Infect. 2012;18:300-7.doi:10.1111/j.1469-0691.2011.03603.
5 Antimicrobial Resistance Surveillance Reference Laboratory, Antimicrobial Resistance Surveillance Program 2012 Annual Report. Manila,
Philippines;2012.
6 Antimicrobial Resistance Surveillance Reference Laboratory, Antimicrobial Resistance Surveillance Program 2013 Annual Report. Manila,
Philippines;2013.
7 Antimicrobial Resistance Surveillance Reference Laboratory, Antimicrobial Resistance Surveillance Program 2014 Annual Report. Manila,
Philippines;2014.
8 Antimicrobial Resistance Surveillance Reference Laboratory, Antimicrobial Resistance Surveillance Program 2015 Annual Report. Manila,
Philippines;2015.
9 Lodha R, Kabra S, Pandey R.: Antibiotics for community-acquired pneumonia in children. Cochrane Database Syst Rev 2013;(6):
CD004874.doi:10.1002/14651858.CD004874.pub4.
10 Ambroggio L, Test M, Metlay J, Graf T, Blosky M, Macaluso M, Shah S.: Comparative Effectiveness of Beta-lactam Versus Macrolide
Monotherapy in Children with Pneumonia Diagnosed in the Outpatient Setting. Pediatr Infect Dis J 2015;34:839-42. doi:
10.1097/INF.0000000000000740.
11 Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R.: Short-course antibiotic treatment for community-acquired
alveolar pneumonia in ambulatory children: a double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J 2014;33:136-42. doi:
10.1097/INF.000000000000002
12 Florendo S.: Clinical efficacy of 3-day, 5-day versus 7-day twice a day regimen of oral amoxicillin in the treatment of non severe
pneumonia in children 11-59 months: a risk stratification clinical trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric
Researches 2012-2015.
13 Queen M, Myers A, Hall M, Shah S, Williams D, Auger K, Jerardi K, Statile A, Tieder J.: Comparative effectiveness of empiric antibiotics
for community-acquired pneumonia. Pediatrics 2014;133:e23-9.doi: 10.1542/peds.2013-1773.
14 Williams D, Hall M, Shah S, Parikh K, Tyler A, Neuman M, Hersh A, Brogan T, Blaschke A, Grijalva C.: Narrow vs broad-spectrum
antimicrobial therapy for children hospitalized with pneumonia. Pediatrics 2013;132:e1141-8. doi: 10.1542/peds.2013-1614.
15 Dinur-Schejter Y.: Antibiotic treatment of children with community-acquired pneumonia: comparison of penicillin or ampicillin versus
cefuroxime Pediatr Pulmonol. 2013;48:52-8. doi: 10.1002/ppul.22534.
16 Das R, Singh M.: Treatment of severe community-acquired pneumonia with oral amoxicillin in under-five children in developing country: a
systematic review. PLoS One 2013;25;8:e66232. doi: 10.1371/journal.pone.0066232.
17 Brandão A, Simbalista R, Borges I, Andrade D, Araújo M, Nascimento-Carvalho C.: Retrospective analysis of the efficacies of two
different regimens of aqueous penicillin G administered to children with pneumonia. Antimicrob Agents Chemother 2014;58:1343-7.
doi:10.1128/AAC.01951-13.
18 Patel A, Bang A, Singh M, Dhande L, Chelliah L, Malik A, Khadse S; ISPOT Study Group.: A randomized controlled trial of hospital
versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3 - 59 months: The IndiaCLEN Severe
Pneumonia Oral Therapy (ISPOT) Study. BMC Pediatr 2015;15:186.doi:10.1186/s12887-015-0510-9.
40
19 Leyenaar J, Shieh M, Lagu T, Pekow P, Lindenauer P.: Comparative effectiveness of ceftriaxone in combination with a macrolide
compared with ceftriaxone alone for pediatric patients hospitalized with community-acquired pneumonia. Pediatr Infect Dis J
2014;33:387-92. doi: 10.1097/INF.0000000000000119.
20 Amarilyo G, Glatstein M, Alper A, Scolnik D, Lavie M, Schneebaum N, Grisaru-Soen G, Assia A, Ben-Sira L, Reif S.: IV Penicillin G is as
effective as IV cefuroxime in treating community-acquired pneumonia in children. Am J Ther 2014;21:814.doi:10.1097/MJT.
0b013e3182459c28.
21 Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M. Severe Pneumonia Study Group.
Collaborators.: Aweyo F, Awuonda B, Chabi M, Isika N, Kariuki M, Kuria M, Mandi P, Masibo L, Massawa T, Mogoa W, Mutai B, Muriithi G,
Ng'arng'ar S, Nyamai R, Okello D, Oywer W, Wanjala L.: Oral amoxicillin versus benzyl penicillin for severe pneumonia among Kenyan
children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis 2015;60:1216-24. doi: 10.1093/cid/ciu1166.
Clinical Question 7. What treatment should be initially given if a viral etiology is strongly considered?
1 American Academy of Pediatrics, Committee on Infectious Diseases: Recommendations for prevention and control of influenza in children,
2015–2016. Pediatrics 2015;136(4).doi:10.1542/peds.2015-2920.
2 Jefferson T, Jones M, Doshi P, Del Mar C, Hama R, Thompson M, Spencer E, Onakpoya I, Mahtani K, Nunan D, Howick J,
Heneghan C.: Neuraminidase inhibitors for preventing and treating influenza in adults and children (Review). Cochrane Database
Syst Rev 2014;4:CD008965.
3 Kimberlin D, Acosta E, Prichard M, Sanchez P, Ampofo K, Lang D, Ashouri N, Vanchiere J, Abzug M, Abughali N, Caserta M,
Englund J, Sood S, Spigarelli M, Bradley J, Lew J, Michaels M, Wan W, Cloud G, Jester P, Wakeman F and Whitley R,
for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.: Oseltamivir pharmacokinetics,
dosing, and resistance among children aged <2 years with influenza. J Infect Dis. 2013;207(5): 709–720. doi: 10.1093/infdis/jis765.
4 Perez C.: Prevalence of viral pathogens among paediatric patients admitted for pneumonia in a local tertiary hospital. Pediatric Infectious
Disease Society of the Philippines Journal 2012;13:8-14.
5 Suzuki A, Lupisan S, Furuse Y, Fuji N, Saito M, Tamaki R, Galang H, Sombrero L, Mondoy M, Aniceto R, Olveda R, Oshitani H.:
Respiratory viruses from hospitalized children with severe pneumonia in the Philippines. BMC Infect Dis. 2012;12:267.doi:
10.1186/1471-2334-12-267.
6 Wang M, Cai F, Wu X, Wu T, Su X, Shi Y.: Incidence of viral infection detected by PCR and real-time PCR in childhood community-
acquired pneumonia: A meta-analysis. Respirology 2015; 20: 405-412. doi: 10.1111/resp.12472.
7 Self W, Griffin M, Zhu Y, Dupont W, Barrett T, Grijalva C.: The high burden of pneumonia on US emergency departments during the 2009
influenza pandemic. J Infect. 2014; 68(2):156-64. doi:10.1016/j.jinf.2013.10.005.
Clinical Question 8. When can a patient be considered as responding to the current antibiotic?
1 Wolf R, Edwards K, Grijalva C, Self W, Zhu Y, Chappell J, Bramley A, Jain S, Williams D.:Time to clinical stability among children
hospitalized with pneumonia. J Hosp Med 2015;10:380-3. doi: 10.1002/jhm.2370.
2 Izadnegahdar R, Fox M, Thea D, Qazi S.: Pneumonia Studies Group. Frequency and trajectory of abnormalities in respiratory rate, tempera-
ture and oxygen saturation in severe pneumonia in children. Pediatr Infect Dis J 2012;31:8635.doi:10.1097/INF.0b013e318257f8ec.
Clinical Question 9. What should be done if a patient is not responding to current antibiotic therapy?
1 Agweyu A, Kibore M, Digolo L, Kosgei C, Maina V, Mugane S, Muma S, Wachira J, Waiyego M, Maleche-Obimbo E.: Prevalence and
correlates of treatment failure among Kenyan children hospitalized with severe community-acquired pneumonia: a prospective study of the
clinical effectiveness of WHO pneumonia case management guidelines. Trop Med Int Health 2014;19:1310-20.doi: 10.1111/tmi.12368.
2 Webb C, Ngama M, Ngatia A, Shebbe M, Morpeth S, Mwarumba S, Bett A, Nokes D, Seale A, Kazungu S, Munywoki P, Hammitt LL,
Scott J, Berkley J.: Treatment failure among Kenyan children with severe pneumonia--a cohort study. Pediatr Infect Dis J.
2012;31:e152-7.doi:10.1097/INF.0b013e3182638012.
3 Basnet A, Sharma A, Mathisen M, Shrestha P, Ghimire R, Shrestha D, Valentiner-Branth P, Sommerfelt H, Strand T.: Predictors of
duration and treatment failure of severe pneumonia in hospitalized young Nepalese children PLoS One 2015;10:e0122052.doi:
10.1371/journal.pone.0122052.eCollection 2015.
4 Jain D, Sarathi V, Jawalekar S.: Predictors of treatment failure in hospitalized children [3-59 months] with severe and very severe
pneumonia. Indian Pediatr 2013;50:787-9.
Clinical Question 10. When can switch therapy in bacterial pneumonia be started?
In-iw S, Winijkul G, Sonjaipanich S, Manaboriboon B.: Comparison between the Efficacy of Switch Therapy and Conventional Therapy in
Pediatric Community-Acquired Pneumonia. J Med Assoc Thai 2015;98:858-63.
41
8 Ambroggio L, Test M, Metlay J, Graf T, Blosky M, Macaluso M, Shah S.: Adjunct Systemic Corticosteroid Therapy in Children With
Community-Acquired Pneumonia in the Outpatient Setting. J Pediatric Infect Dis Soc 2015 ;4:21-7. doi:10.1093/jpids/piu017.
9 Chaves G, Fregonezi G, Dias F, Ribeiro C, Guerra R, Freitas D, Parreira V, Mendonca K.: Chest physiotherapy for pneumonia in children.
Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD010277. DOI: 10.1002/14651858.CD010277.pub2.
10 Das R, Singh M, Panigrahi I, Naik S.: Vitamin d supplementation for the treatment of acute childhood pneumonia: a systematic review.
ISRN Pediatr. 2013;2013:459160. doi: 10.1155/2013/459160. eCollection2013.
11 Doctor-Bernabe J, Ampil I, Bibera G.: Effect of zinc supplementation as an adjunct in the treatment of pneumonia in children ages 2 to 59
months: a meta-analysis. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
12 Macalino MV, Dans L, Lorenzana R.: Zinc as adjunct to antibiotics in the treatment of severe pneumonia in children aged two months to
five years: a meta-analysis. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
13 Wadhwa N, Chandran A, Aneja S, Lodha R, Kabra S, Chaturvedi M, Sodhi J, Fitzwater S, Chandra J, Rath B, Kainth U, Saini S, Black R,
Santosham M, Bhatnagar S.: Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized
children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2013;97:1387-
94.doi:10.3945/ajcn.112.052951.
14 Sempértegui, Estrella B, Rodríguez O, Gómez D, Cabezas M, Salgado G, Sabin L, Hamer D.: Zinc as an adjunct to the treatment of severe
pneumonia in Ecuadorian children: a randomized controlled trial. Am J Clin Nutr 2014;99:497-505.doi: 10.3945/ajcn.113.067892.
15 Shah G, Dutta A, Shah D, Mishra O.: Role of zinc in severe pneumonia: a randomized double bind placebo controlled study. Ital J Pediatr
2012;38:36. doi: 10.1186/1824-7288-38-36.
16 Srinivasan M, Ndeezi G, Mboijana C, Kiguli S, Bimenya G, Nankabirwa V and Tumwine J.: Zinc adjunct therapy reduces case fatality in
severe childhood pneumonia: a randomized double blind placebo-controlled trial. Medicine 2012;10:14.
17 Fataki M, Kisenge R, Sudfeld C, Aboud S, Okuma J, Mehta S, Spiegelman D, Fawzi W.: Effect of zinc supplementation on duration of
hospitalization in Tanzanian children presenting with acute pneumonia. J Trop Pediatr 2014;60:104-11.doi:10.1093/tropej/fmt089.
18 Becina P, Peralta K, Becina G.: A double-blind, randomized, controlled trial of the efficacy of multiple strain probiotics as adjunct therapy
for patients [2 months-4 years old] with moderate risk community-acquired pneumonia admitted at National Children’s Hospital.
Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
19 Villanueva J, Matheus J.: A randomized controlled trial on the effects of oral folate in the treatment of pediatric community-acquired
pneumonia-c among infants ages 2-12 months admitted at the pediatric ward of Dr. Jose Fabella Memorial Hospital. Philippine
Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
20 Mondragon A.: The efficacy of oral vitamin D3 supplementation on the severity of pneumonia in children ages 3 months – 60 months: a
randomized double-blind controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
21 Martinez M.:The efficacy of acetylcysteine nebulization as an adjunct therapy for community-acquired pneumonia-C in children aged 3 to 60
months admitted at a tertiary government hospital. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
22 Delizo M, Resurreccion E.: Nebulization using normal saline solution or bronchodilators as adjunct treatment in children hospitalized with
community-acquired pneumonia: a retrospective study Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
23 Dalangin B.: A randomized controlled trial on the efficacy and safety of probiotic [Bacillus claushii] and zinc as adjuncts in the treatment
of pediatric community-acquired pneumonia among 1 to 10 years old in an outpatient department at a private hospital. Philippine
Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
24 Dionisia-Delfin,T.:The effectiveness of spirulina as an adjunct in the treatment of pediatric community-acquired pneumonia C among children
aged 2-5 years: a randomized placebo controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
25 Vierneza M.: The effectiveness of virgin coconut oil as adjunct treatment of pediatric community acquired pneumonia: a randomized
controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
42
12 Martinelli D, Pedalino B, Cappelli M, Caputi G, Sallustio A, Fortunato F, Tafuri S, Cozza V, Germinario C, Chironna M, Prato R; Apulian
Group for the surveillance of pediatric IPD.: Towards the 13-valent pneumococcal conjugate universal vaccination: effectiveness in the
transition era between PCV7 and PCV13 in Italy, 2010-2013. Hum Vaccin Immunother 2014;10:33-9. doi:10.4161/hv.26650.
13 Saxena S, Atchison C, Cecil E, Sharland M, Koshy E, Bottle A.: Additive impact of pneumococcal conjugate vaccines on pneumonia and
empyema hospital admissions in England. J Infect 2015;71:428-36. doi: 10.1016/j.jinf.2015.06.011.
14 Griffin M, Mitchel E, Moore M, Whitney C, Grijalva C; Centers for Disease Control and Prevention (CDC).: Declines in pneumonia
hospitalizations of children aged <2 years associated with the use of pneumococcal conjugate vaccines -Tennessee,1998-2012.
MMWR Morb Mortal Wkly Rep. 2014;63:995-8
15 Greenberg D, Givon-Lavi N, Ben-Shimol S, Ziv JB, Dagan R.: Impact of PCV7/PCV13 introduction on community-acquired alveolar
pneumonia in children <5 years. Vaccine 2015;33(36):4623-9. doi: 10.1016/j.vaccine.2015.06.062.
16 Abrão W, de Mello L, da Silva A. Nunes A.: Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious respiratory
diseases and hospitalization rates in children. Rev Soc Bras Med Trop 48:44-49.
17 Afonso E, Minamisava R, Bierrenbach A, Escalante J, Alencar A, Domingues C, Morais-Neto O, Toscano C, Andrade A.: Effect of 10-
valent pneumococcal vaccine on pneumonia among children. Brazil Emerg Infect Dis 2013;19:589-97. doi:10.3201/eid1904.121198.
18 Tregnaghi M, Sáez-Llorens X, López P, Abate H, Smith E, Pósleman A, Calvo A, Wong D, Cortes-Barbosa C, Ceballos A, Tregnaghi M,
Sierra A, Rodriguez M,Troitiño M, Carabajal C, Falaschi A, Leandro A, Castrejón M, Lepetic A, Lommel P, Hausdorff WP, Borys D, Ruiz
Guiñazú J, Ortega-Barría E, Yarzábal JP, Schuerman L; COMPAS Group.: Efficacy of pneumococcal nontypable Haemophilus influenza
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19 Flasche S, Takahashi K, Vu D, Suzuki M, Nguyen T, Le H, Hashizume M, Dang D, Edmond K, Ariyoshi K, Mulholland EK, Edmunds W,
Yoshida L.: Early indication for a reduced burden of radiologically confirmed pneumonia in children following the introduction of routine
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20 Ekaru H, Mbarak N, Shurie S, Kosgei E, Oyungu E, Kwena A.: Community acquired pneumonia among children admitted in a tertiary
hospital: the burden and related factors. East Afr Med J 2012;89:301-5.
21 Grant C, Emery D, Milne T, Coster G, Forrest C, Wall C, Scragg R, Aickin R, Crengle S, Leversha A, Tukuitonga C, Robinson E.: Risk
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1754.2011.02244.x.
22 Tomas A, Resurreccion M.: A hospital based case control study on the association of selected maternal risk taking behaviors in the
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23 Barsam F, Borges G, Severino A, de Mello L, da Silva A, Nunes A.: Factors associated with community-acquired pneumonia in
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43
APPENDIX. Summary recommendations of 2004 Clinical Practice Guideline in
the Evaluation and Management of Pediatric Community-acquired Pneumonia,
and 2008 1st PAPP Update in the Evaluation and Management of Pediatric
Community-acquired Pneumonia.
CQ 1. WHO SHALL BE CONSIDERED AS HAVING COMMUNITY ACQUIRED PNEUMONIA?
44
CQ 5. WHEN IS ANTIBIOTIC RECOMMEDED
2004 SUMMARY RECOMMENDATION.
An antibiotic is recommended
1. for a patient classified as either pCAP A or B and is 1.1. beyond 2 years of age [Recommendation Grade B]; or
1.2. having high-grade fever without wheeze [Recommendation Grade D].
2. for a patient classifed as pCAP C and is 2.1. beyond 2 years of age [Recommendation Grade B]; or
2.2. having high-grade fever without wheeze [Recommendation Grade D]; or
2.3. having alveolar consolidation on the chest x-ray [Recommendation Grade B]; or
2.4. having white blood cell count > 15,000 [Recommendation Grade C].
3. for a patient classified as pCAP D [Recommedation D].
45
CQ 8. WHEN CAN A PATIENT BE CONSIDERED AS RESPONDING TO THE CURRENT ANTIBIOTIC?
2004 SUMMARY RECOMMENDATION.
1. Decrease in respiratory signs [particularly tachypnea] and defervescence within 72 hours after initiation of antibiotic are predictors of
favorable therapeutic response [Recommendation Grade D].
2. Persistence of symptoms beyond 72 hours after initiation of antibiotics requires reevaluation [Recommendation Grade B].
3. End of treatment chest x-ray [Recommendation Grade B], WBC, ESR or CRP should not be done to assess therapeutic response to
antibiotic [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. In children with nonsevere pneumonia, clinical index suggestive of good therapeutic response is a respiratory rate >5 breaths/min slower
than baseline recording at the 72nd hour.
2. In children with severe pneumonia, clinical indices suggestive of good therapeutic response are defervescense, decrease in tachypnea
and chest indrawing, increase in oxygen saturation, and ability to feed within 48 hours.
1. Among inpatients, oxygen and hydration should be given if needed [Recommendation Grade D].
2. Cough preparations, chest physiotherapy, bronchial hygiene, nebulization using normal saline solution, steam inhalation, topical
solution, bronchodilators and herbal medicines are not routinely given in community-acquired pneumonia [Recommendation Grade D].
3. In the presence of wheezing, a bronchodilator may be administered [Recommendation Grade D].
1. Vaccines recommended by PPS should be routinely administered to prevent pneumonia [Recommendation Grade B].
2. Zinc supplementation [10 mg for infants and 20 mg for children beyond two years of age given for a total of 4 to 6 months] may be
administered to prevent pneumonia [Recommendation Grade A].
3. Vitamin A [Recommendation Grade A], immunomodulators [Recommendation Grade D] and vitamin C [Recommendation Grade D]
should not be routinely administered as a preventive strategy.
46