An Official Publication of the
Philippine Academy of Pediatric Pulmonologists, Inc.
PAPP PERSPECTIVE
3rd PAPP Update [2016]
in the
Evaluation and Management of
Pediatric Community-acquired Pneumonia
2016 PAPP Task Force on pCAP
PHILIPPINE ACADEMY OF PEDIATRIC PULMONOLOGISTS, Inc. [PAPP, Inc.]
rd
2016 PAPP Task Force on pCAP: 3 PAPP Update [2016] in the Evaluation and Management
of Pediatric Community-acquired Pneumonia.
All rights reserved. Publication and request for permission to reproduce should be obtained from the
Philippine Academy of Pediatric Pulmonologists, Inc., Room 4, 4/F Philippine Pediatric Society
Building, 52 Kalayaan Avenue, Barangay Malaya, Quezon City 1100 Philippines. Telefax Number [632]
3328855. Email address: papp_office@yahoo.com. Website:http://www.papp.org.ph
PHILIPPINE ACADEMY OF PEDIATRIC PULMONOLOGISTS, Inc. [PAPP, Inc.]
2016-2017 Board of Directors
Mary Therese M. Leopando, MD FPPS FPAPP
President
Mary Ann F. Aison, MD FPPS FPAPP
Vice president
Regina M. Canonizado, MD FPPS FPAPP
Secretary
Nepthalie R. Ordonez, MD FPPS FPAPP
Treasurer
Anna Marie S. Putulin, MD FPPS FPAPP
Director
Amelia G. Cunanan, MD FPPS FPAPP
Director
Lydia K. Chang, MD FPPS FPAPP
Director
Clara R. Rivera, MD FPPS FPAPP
Immediate past president
2016 PAPP Task Force on pCAP
Cristan Q. Cabanilla, MD FPPS FPAPP
Emily B. Gaerlan-Resurreccion, MD FPPS FPAPP
Vivian A. Ancheta, MD FPPS FPAPP
Gari D. Astrologio, MD DPPS DPAPP
Janet C. Bernardo, MD FPPS FPAPP
Alfredo L. Bongo Jr, MD FPPS FPAPP
Janet Myla Q. Bonleon, MD FPPS FPAPP
Lydia K. Chang, MD FPPS FPAPP
Edward A. Chua, MD DPPS DPAPP
Julie Iris C. Clapano, MD FPPS DPAPP
Amelia G. Cunanan, MD FPPS FPAPP
Beverly D. de la Cruz, MD FPPS DPAPP
Anjanette R. de Leon, MD FPPS FPAPP
Yadnee V. Estrera, MD DPPS DPAPP
Jean Marie E. Jamero, MD DPPS DPAPP
Arnold Nicholas T. Lim, MD DPPS DPAPP
Grace V. Malayan, MD FPPS FPAPP
Beatriz Praxedez Apolla I. Mandanas, MD DPPS DPAPP
Raymund Anthony L. Manuel, MD DPPS DPAPP
Vicente Carlomagno D. Mendoza, MD FPPS DPAPP
Doris Louise C. Obra, MD FPPS FPAPP
Catherine S. Palaypayon, MD DPPS DPAPP
Cynthia Theresa M. Rimando, MD FPPS DPAPP
Ernesto Z. Salvador, MD DPPS DPAPP
Marion O. Sanchez, MD FPPS FPAPP
Josy Naty M. Venturina, MD DPPS DPAPP
Rozaida R. Villon, MD FPPS FPAPP
Nilyn Elise O. Ygnacio, MD DPPS DPAPP
Dahlia L. Yu, MD DPPS DPAPP
Chair
Secretary
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
Member
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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.
Mary Therese M. Leopando, MD FPPS FPAPP
President
Philippine Academy of Pediatric Pulmonologists, Inc.
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.
Key differences between the 2
SECTION
nd
rd
and 3 Updates are summarized below.
KEY DIFFERENCES
2012
2016
A. Methodology
1. Microbial etiology
Virus, bacteria and Mtb
2. Geographic distribution of
MetroManila
Task force membership
3. Literature review
Jan 2008 to Dec 2011
4. Definition of level of
Based on Sacket DL,
evidence and grading
Straus SE: Evidence
of recommendation
Based Medicine 2000
5. Geographic distribution of
MetroManila
stakeholders
Virus and bacteria
MetroManila, MetroCebu and MetroDavao
Jan 2012 to Dec 2016
Developed by the 2016 PAPP Task Force in pCAP
Nationwide
B. Summary recommendations
1. Appraisal
Clinical Question1
Clinical Question 2
Clinical Question 3
Clinical Question 4
Clinical Question 5
2. Therapeutic approach
Clinical Question 6
Clinical Question 7
Clinical Question 8
Clinical Question 9
Clinical Question 10
Clinical Question 11
3. Preventive strategies
Clinical Question 12
1. Predictors to detect radiographic pneumonia
a. Higher threshold for Sa02
b. Additional indeces
2. Addition of negative predictors for radiographic pCAP
3. Revised indications for requesting chest xray at initial
site-of-care
No significant change
No significant change
1. Addition of lung ultrasound and anaerobic culture
as diagnostic tests
2. Removal of diagnostic test for tuberculosis
1. Additional test to determine necessity of antibiotic
administration
2. No recommendation for pCAP A or B
No significant change
Addition of zanamivir
Addition of deifinition of clinical stability
No significant change
No significant change
Zinc may be beneficial
Zinc may not be beneficial
Cristan Q. Cabanilla, MD FPAPP FPPS
Chair
2016 PAPP Task Force on pCAP
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.
B. Intended target users
The intended users are medical practitioners involved in the care of patients with community-acquired pneumonia.
C. Technical Working Group
A technical working group has been designated by the PAPP 2016 Task Force on pCAP t o search for relevant
literature, appraise clinical evidence, and formulate recommendations.
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. GaerlanResurreccion, Ernesto Z. Salvador, Marion O. Sanchez, Josy Naty M. Venturina, Rozaida R. Villon, Nilyn
Elise O. Ygnacio, and Dahlia L. Yu.
E. Clinical questions pertaining to evaluation, treatment and prevention
The Task Force has decided to maintain the same clinical questions that were formulated in the 2004 Clinical
Practice Guideline in the Evaluation and Management of Pediatric Community-acquired Pneumonia, 2008
st
nd
PAPP 1 Update, and 2012 PAPP 2 Update in the Evaluation and Management of Pediatric Communityacquired Pneumonia, except clinical questions 8 and 9. The scope of both questions has become broader to
include viral pneumonia.
1. Who shall be considered as having community-acquired pneumonia?
2. Who will require admission?
3. What diagnostic aids are initially requested for a patient classified as either pCAP A or pCAP B being
managed in an ambulatory setting?
4. What diagnostic aids are initially requested for a patient classified as either pCAP C or pCAP D being
managed in a hospital setting?
5. When is antibiotic recommended?
6. What empiric treatment should be administered if a bacterial etiology is strongly considered?
7. What treatment should be initially given if a viral etiology is strongly considered?
8. When can a patient be considered as responding to the current therapeutic management?
9. What should be done if a patient is not responding to the current therapeutic management?
10. When can switch therapy in bacterial pneumonia be started?
11. What ancillary treatment can be given?
12. How can pneumonia be prevented?
F. Literature search, and inclusion and appraisal of evidence
Local researches submitted to the Philippine Pediatric Society [PPS] and published at the Abstracts Philippine
Pediatric Researches 2012-2015, Philippine Academy of Pediatric Pulmonologists [PAPP], and Pediatric Infectious
Disease Society of the Philippines [PIDSP] Journal, and foreign literature identified using the PubMed database were
searched and limited to the following: [1] source of data from January 1, 2012 to December 31, 2015; [2] 3 months to
19 years of age; and [3] immunocompetent host. Relevant clinical practice guidelines in children and studies in the
adult population were reviewed but not used as evidence for recommendation. Systematic reviews, review articles,
commentaries, a n d case reports or series were excluded. Publication bias potentially existed as published local
articles other than what had been submitted to PPS, PAPP and PIDSP Journal, and unpublished local or foreign
articles were not searched.
Appraisal of evidence and interpretation of results were done based on Dans AL, Dans LF, Silvestre MAA:
Painless Evidence-Based Medicine 2008, England John Wiley and Sons & Ltd.
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.
H. Grade recommendation with description of level of evidence
Starting with the 2016 Third PAPP Update, The Task Force developed a grading of recommendation supported
by corresponding levels of evidence, as follows:
GRADE
A
B
RECOMMENDATION STATEMENT
Should [or should not] be recommended1 .
Strong evidence exists to [or not to] be
recommended but with reservation2.
A1
A2
B1
May [or may not ] be recommended.
B2
May [or may not] be recommended but with
reservation2.
C1
C
D
C2
May [or may not] be recommended.
May [or may not] be recommended but with
reservation2.
DESCRIPTION OF EVIDENCE
Definite evidence for benefit [or without benefit] based on at least 1 metaanalysis of descriptive or randomized controlled trials, or at least 2 separate
descriptive or randomized controlled trials, with similar intervention, study
design, outcome AND result.
Equivocal evidence for benefit [or without benefit] based on multiple metaanalysis of descriptive or randomized controlled trials, or at least 2 separate
descriptive or randomized trials with dissimilar intervention, outcome, study
design OR results.
Evidence for benefit [or without benefit] based on only one descriptive or
randomized controlled trial.
Evidence for benefit [or without benefit] based on consensus opinion of at
least three-fourths of committee members of each clinical question
1
Recommendation as a routine [or not a routine] intervention.
2
Conditional recommendation. Evidence exists BUT with reservations to recommend as to cost, availability, or a consensus among
the members of the Task Force that more similar studies are needed before an appropriate recommendation can be made.
May [or may not] be recommended.
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.
J. Formulation of the final draft
At least three-fourths of the members of the Task Force met through teleconferencing, and voted unanimously
for each recommendation. Any disagreements on any recommendation were resolved by votation of at least
three-fourths of all members.
K. Approval by the 2016-2017 PAPP Board of Directors
The final draft was approved by....
L. Source of funding
Internal funding was provided by the Philippine Academy of Pediatric Pulmonologists, Inc. There were no
sources for external funding.
M. Dissemination and periodic evaluation
Dissemination is through the Philippine Academy of Pediatric Pulmonologists [PAPP]. Digital version can be
downloaded free at the PAPP website for a limited time, while a hard copy is available at the PAPP office.
Future periodic evaluation using a questionnaire survey looking at [1] acceptability by the end-user, [2]
utilization in clinical practice, and [3] identification of gaps in knowledge will be done each year by the PAPP
Task Force on pCAP, and distributed to clinicians attending the PAPP Annual Convention. Results of the
th
periodic evaluation will be used for formulating the 4 PAPP Update in the Evaluation and Management of
Pediatric Community-acquired Pneumonia [2020].
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
PEDIATRIC COMMUNITY-ACQUIRED PNEUMONIA
Clinical Questions
Subcommittee Members
Background: 2nd PAPP Update [2012] Recommendations
3rd PAPP Update [2016] Recommendations
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].
2016 KEY RECOMMENDATIONS**
1. A patient presenting initially with cough and/or respiratory difficulty may be evaluated for possible
presence of pneumonia [Recommendation Grade B2].
1.1. Pneumonia may be considered if any of the following positive predictors of radiographic
pneumonia is present.
At the Emergency Room as the site-of-care.
1.1.1. Oxygen saturation less than or equal to 94% at room air in a patient aged 3 months to 5 years
[Recommendation Grade B2], and above 5 years old [Recommendation Grade C2] in the absence of any comorbid
neurologic, musculoskeletal or cardiac conditions that may potentially affect oxygenation
[Recommendation Grade D].
1.1.2. Tachypnea [age-specific as defined by World Health Organization [WHO] in a patient
aged 3 months to 5 years [Recommendation Grade B2], and above 5 years old [Recommendation Grade D].
1.1.3. Chest wall retractions in a patient aged 3 months to 5 years [Recommendation Grade B2], and
above 5 years old [Recommendation Grade D].
1.1.4. Fever [Recommendation Grade B2], grunting, wheezing, decreased breath sounds, nasal flaring,
cyanosis, crackles or localized chest findings at any age [Recommendation Grade C2].
1.1.5. Consolidation as visualized in lung ultrasound [Recommendation Grade B2].
At the Out-Patient Clinic as the site-of-care.
1.1.6. Oxygen saturation less than or equal to 94% at room air in the absence of any comorbid neurologic, musculoskeletal or cardiac conditions that may potentially affect oxygenation; tachypnea
[age-specific as defined by WHO]; chest wall retractions; fever; decreased breath sounds; nasal
flaring; cyanosis; crackles; or localized chest findings at any age [Recommendation Grade D].
1.2. Pneumonia may not be considered if any of the following negative predictors of radiographic
pneumonia is present.
At the Emergency Room as the site-of-care.
1.2.1. Oxygen saturation greater than 94% at room air in a patient aged 3 months to 5 years
[Recommendation Grade C2], and above 5 years old [Recommendation Grade D].
1.2.2. Absence of fever, nasal flaring and chest wall retractions in a patient aged 3 months to
5 years [Recommendation Grade C2], and above 5 years old [Recommendation Grade D].
At the Out-Patient Clinic as the site-of-care.
1.2.3. Oxygen saturation greater than 94% at room air, and absence of fever, nasal flaring or
chest wall retractions [Recommendation Grade D].
2. Chest x-ray may be requested to determine the presence of pneumonia in any of the following situations:
2.1. Dehydration in a patient aged 3 months to 5 years [Recommendation Grade C2].
2.2. High index of clinical suspicion [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 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
AGE
[n]
Positive
Negative
Emergency room as the site of care
INITIAL PRESENTATION
Cough or difficulty of breathing
147
Cough or difficulty of breathing
and
WHO-defined, age-specific tachypnea
324
58%
<5y
34%
AUTHOR/YEAR
42%
Modi P,2013
---
Wingerter S,2012
3. Predictors of pneumonia with chest x-ray as the reference standard
3.1. Positive predictors
PATIENTS
[n]
PREDICTOR
AGE
ODDS RATIO
[95%CI]
SPECIFICITY
POSITIVE
p
PREDICTIVE VALUE
VALUE
AUTHOR / YEAR
Emergency room as site-of-care
1
Oxygen saturation
<90%
<92%
<94%
Clinical presentation
Difficulty of breathing
Tachypnea
147
126
3,204
<5y
6m-18y
1m-5y 5.90 (3.55-9.80)
165
1-16y
[WHO-defined, age-specific]
147
<5y
Tachypnea
3,204
1m-5y
147
3,204
147
126
<5y
1m-5y 2.11 (1.35-3.32)
<5y
6m-18y
[PALS cut-off, age specific]
Chest wall retractions
Fever
Grunting
Wheezing
Decreased breath sounds
Nasal flaring
Cyanosis
Localized chest findings
2
Predictive score
>9
Lung ultrasound
Consolidation
68%
63%
72%
<5y
126
6m-18y
300
3m–5y
765
<18y
Alagadan S,2015
Modi P,2013
Nijman R,2013
1.55 (0.99-2.42)
8-11%
6%
100%
40%
38%
18%
5%
147
Modi P,2013
0.01 Muthukrishnan L,2013
Nijman R,2013
Modi P,2013
Nijman R,2013
Modi P,2013
0.006 Muthukrishnan L,2013
Modi P,2013
0.001 Muthukrishnan L,2013
95.7%
(87.2%–98.9%)
Emergency room or ward as site-of-care
Arquiza T,2013
3
84% (80%–88%)
Outpatient clinic as site-of-care
Pereda M,2015
Risk predictive score2
> 35.8
120
3m-5y
100%
Domingo E, 2013
1
Determination of oxygen saturation at room air is desirable in situation where pulse oximeter is available.
2
Unlike the individual parameters which have been mentioned in previous literature, these corresponding predictive scores have
been only recently submitted to the Philippine Pediatric Society and Philippne Academy of Pediatric Pulmonolgists. It is the
consensus among the Task Force members that more studies are needed to assess their reliability and applicability in varying
clinical settings. As such, no definite recommendations using predictive scoring system can be given at this point in time.
3
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.
11
3.2. Negative predictors
PATIENTS
AGE
[n]
Emergency room as site-of-care
PREDICTOR
Oxygen saturation
SENSITIVITY
AUTHOR/YEAR
1
<94%
Clinical presentation
Fever
Nasal flaring
Chest wall retractions
Decreased breath sounds
Wheezing
Grunting
Tachypnea
[WHO defined. age-specific]
86%
147
<5y
93%
91%
81-85%
70%
44%
40%
Modi P,2013
37%
Emergency room or ward as site-of-care
Lung ultrasound
1
2
2
Consolidation
765
<18y
96% (94%–98%)
Pereda M,2013
Determination of oxygen saturation at room air is desirable in situation where pulse oximeter is available.
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.
4. Specific clinical situation in which chest x-ray is needed
Impact of metabolic derangement on clinical predictor of radiographic pneumonia
METABOLIC DERANGEMENT
STUDY DESIGN
Diarrhea with hypokalemia
Prospective cohort
PATIENTS
[n]
180
ODDS RATIO
CLINICAL PREDICTOR
FOR CLINICAL PREDICTOR
OF
OF RADIOGRAPHIC
AUTHOR/YEAR
RADIOGRAPHIC
PNEUMONIA
PNEUMONIA
[CI 95%]
Emergency room as site-of-care
AGE
0-59m
Tachypnea
0.36 [0.17-0.34] p=0.005
Chisti M,2013
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
Philippine Health Insurance Corporation
World Health Organization
pCAP A or B
--Nonsevere
pCAP C
Pneumonia I
Severe
pCAP D
Pneumonia II
Very severe
Mild
None
None
>50/min to <60/min
>40/min to <50/min
>30/min to <35/min
Moderate
Moderate
Present
>60/min to <70/min
>50/min
>35/min
Severe
Severe
Present
>70/min
>50/min
>35/min
None
None
None
None
None
None
Intercostal / subcostal
Present
Present
None
None
Irritable
Supraclavicular / IC / subcostal
Present
Present
Present
Present
Lethargic / stuporous / comatose
None
Present
Present
95%
<95%
<95%
Outpatient
End of treatment
Admit to ward
Admit to a critical care facility
b
VARIABLES
Clinical
1. Dehydrationc
2. Malnutritiond
3. Pallor
4. Respiratory rate
None
a. 3 to12 months
b. 1 to 5 yearse
c. >5 years
e
5. Signs of respiratory failure a. Retraction
b. Head bobbing
c. Cyanosis
d. Grunting
e. Apnea
f. Sensorial changes
f
Diagnostic aid at site-of-care
1. Chest x-ray findings of any of the following: effusion;
abscess; air leak or lobar consolidation
2. Oxygen saturation at room air using pulse oximetry
ACTION PLAN
1. Site-of-care
2. Follow-up
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.
Risk factors for mortality based on evidence and/or expert opinion among members of the 2012 PAPP Task Force on pCAP.
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.
b
c
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.
2016 KEY RECOMMENDATIONS**
1. A patient may be classified as pCAP A, B, C or D within 48 hours after consultation based on the
following risk classification for pneumonia-related mortality [Recommendation Grade D].
RISK CLASSIFICATION1
PARAMETERS IDENTIFIED
AT
pCAP A
pCAP B
pCAP C
pCAP D
INITIAL SITE-OF-CARE
Severe or moderate risk
Very severe or high risk
Nonsevere
Clinical parameters2
1. Respiratory signs
1.1. Retraction
None
Intercostal / subcostal
Supraclavicular / IC / subcostal
1.2. Head bobbing
None
Present Present
Present
1.3. Cyanosis
None
None
Present
1.4. Grunting
None
None
Present
1.5. Apnea
None
Present
1.6. Tachypnea
>60/min to <70/min
3
1.6.1. 3 to12 months
>50/min to <60/min
>50/min
>70/min
1.6.2. 1 to 5 years3
>35/min
>40/min to <50/min
>50/min
1.6.3. >5 years
>30/min to <35/min
>35/min
1
In order to classify to a higher risk category, at least 2 parameters [clinical and/or ancillary] may be present. In the absence of
an ancillary parameter, clinical parameters may suffice.
2
Risk factors for mortality based on evidence and/or expert opinion among members of the 2016 PAPP Task Force on pCAP.
3
World Health Organization age-specific criteria for tachypnea for children under 5 years old.
*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
2.2. Convulsion
3. Circulatory signs
3.1. Poor perfusion
3.2. Pallor
4. General considerations
4.1. Malnutrition4
4.2. Inability to drink
4.3. Comorbid conditions
None
None
Irritable
Present
Lethargic / stuporous / comatose
Present
None
None
Capillary refill >3s
Present
Shock
Present
Moderate
Yes
Present
Severe
Yes
Present
None
Present
Present
95%
91% to 94%
<90%
None
No
None
Mild No
Present
Ancillary parameters5
5. Chest x-ray findings of effusion,
abscess, air leak or multilobar
consolidation
6. Oxygen saturation at room air using
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
DESIGN
AGE
RISK FACTORS
n/N [%]
49/85 [57.6%]
Severe malnutrition
Altered consciousness
<59m
Cohort
22/85 [25.9%]
Convulsion
Age
1 to 6m
2 to11m
49/85 [57.7%]
Shock
<12y
2
4/85 [4.7%]
Increasing severity
Inability to drink
Congenital heart disease 10/85 [11.8%]
Head nodding
<59m
Central cyanosis
Grunting
SpO2 <90%
1
2
Radiologic pneumonia cases
Multivariate analysis
ODDS RATIO
[95%CI]
1.85 (1.03-3.32)
1.91 (0.67–4.92)
1.37 (0.35–5.31)
14.49 (4.49-51.88)
1.02 (0.40–2.59)
11.15 (3.38-40.59)
6.83 (2.01–23.2)
2.77 (1.57-4.91)
1.80 (0.57–5.67)
9.99 (3.36–29.7)
0.51 (0.14-1.72)
3.20 (1.20-8.90)
6.39 (1.40–29.23)
5.53 (1.53-21.72)
2.15 (0.84–5.50)
1.85 (0.56–6.08)
0.71(0.27–1.86)
0.31 (0.07–1.42)
P
VALUE
0.020
0.230
0.001
0.970
0.001
0.001
0.310
0.230
0.020
0.006
0.001
0.100
0.300
0.490
0.110
AUTHOR/YEAR
1
Ramachandran P,2012
Agweyu A,2014
Webb C, 2012
Ramachandran P,20121
Agweyu A,2014
Ramachandran P,20121
Webb C 2012
1
Ramachandran P,2012
Agweyu A,2014
Webb C,2012
Ramachandran P,20121
Ferreira S,2014
Agweyu A,2014
1
Ramachandran P,2012
Agweyu A,2014
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
DESIGN
AGE
RCT
<59m
INTERVENTION
7 days oral amoxicillin at home
vs
7 days oral amoxicillin for 48 hours at
hospital followed by 5 days at home
MORTALITY TREATMENT FAILURE RATE
AUTHOR/YEAR
RATE
AT DAY 14
0.2% [1/554]
10.8% (60/554)
vs
Patel A,2015
vs
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].
2016 KEY RECOMMENDATIONS**
1. The following may be requested at initial site-of-care
Clinically important endpoint: assessment of gas exchange
1.1. Oxygen saturation using pulse oximetry [Recommendation Grade D].
Clinically important endpoint: microbial determination of underlying etiology
1.2. Gram stain and/or aerobic culture and sensitivity of sputum [Recommendation Grade D]
Clinically important endpoint: clinical suspicion of necrotizing pneumonia, multilobar consolidation,
lung abscess, pleural effusion, pneumothorax or pneumomediastinum
1.3. Chest x-ray PA-lateral [Recommendation Grade D]
1.4. Chest ultrasound [Recommendation Grade D]
2. The following may not be requested.
Clinically important endpoint: microbial determination of underlying etiology
2.1. Blood culture and sensitivity [Recommendation Grade D]
Clinically important endpoint: basis for initiating antibiotic treatment
2.2. White blood cell [WBC] count [Recommendation Grade D]
2.2. C-reactive protein [CRP] [Recommendation Grade D]
2.4. Procalcitonin [PCT) [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]
2016 KEY RECOMMENDATIONS**
1. For pCAP C and pCAP D, the following diagnostic aids may be requested at initial site-of-care.
Clinically important endpoint: assessment of gas exchange
1.1. Oxygen saturation using pulse oximetry [Recommendation Grade D]
1.2. Arterial blood gas [Recommendation Grade D]
Clinically important endpoint: Surrogate markers for possible presence of pathogens requiring initial
empiric antibiotic with microbiology as the reference standard
1.3. C-reactive protein [CRP] [Recommendation Grade B1]
1.4. Procalcitonin [PCT] [Recommendation Grade B1]
1.5. Chest x-ray PA-lateral [Recommendation Grade C2]
1.6. White blood cell [WBC] [Recommendation Grade C2]
Clinically important endpoint: clinical suspicion of necrotizing pneumonia, multilobar consolidation,
lung abscess, pleural effusion, pneumothorax or pneumomediastinum.
1.7. Chest x-ray PA-lateral [Recommendation Grade C1]
1.8. Chest ultrasound [Recommendation Grade B2]
Clinically important endpoint: determination of underlying microbial etiology
1.9. Gram stain and/or aerobic culture and sensitivity of sputum, nasopharyngeal aspirate and/or
pleural fluid, and/or blood for pCAP C with lung abscess, empyema or pneumothorax
[Recommendation Grade C1]
1.10. Gram stain and/or aerobic culture and sensitivity of sputum, tracheal aspirate and/or pleural fluid, for
pCAP D [Recommendation Grade D]
1.11. Anaerobic culture and sensitivity of sputum, nasopharyngeal aspirate, pleural fluid, and/or blood
culture and sensitivity for [Recommendation Grade D]
1.11.1. pCAP C with lung abscess, empyema or pneumothorax
1.11.2. pCAP D
1.12. Serum IgM for Mycoplasma pneumoniae [Recommendation Grade B2]
*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.
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
PATHOGEN
STUDY DESIGN
C-reactive protein [CRP] : >80 mg/L
Bacterial/atypical vs viral pathogen
Prospective cohort
CRP : elevated
Pneumococcal vs viral pathogen
Prospective cohort
CRP : elevated
Bacterial vs viral pathogen
Retrospective cohort
CRP : > 200 ug/ml
Bacterial pathogen
Case control
CRP : abnormal
Mycoplasma p vs non-Mycoplasma p
Cross-sectional
Procalcitonin [PCT] : elevated
Bacterial vs non-bacterial pathogen
Prospective cohort
PCT : elevated
Pneumococcal vs non-bacterial pathogen
Retrospective cohort
Lipocalin 2 : >130.1 ng/ml
Probable bacterial pathogen
Case control
Chest x-ray : pneumonia
Pneumococcal infection
Cross-sectional
IgM assay : 1.65 mean value
Mycoplasma pneumoniae
Cross-sectional
White blood cell count [WBC] : abnormal
Mycoplasma p vs non-Mycoplasma p
Cross-sectional
WBC : abnormal
Bacterial vs non-bacterial pathogen
Cohort
WBC : >15 × 109/L
Bacterial vs viral pathogen
Prospective cohort
ODDS RATIO
[95% CI]
YIELD
[%]
3.6
[1.65–8.07]
p VALUE
SPECIFICITY
[95% CI]
0.001
Elemraid M,2014
19
[5-75]
Galetto-Lacour A,2013
0.020
Hoshina T,2014
56.10%
30.9%
vs
23.7%
0.002
Huang H,2014
Gao J,2015
23
[5-117]
Galetto-Lacour A,2013
0.0008
65.5%
vs
55.2%
0.5
[0.13–1.96]
AUTHOR/YEAR
Hoshina T,2014
85.7%
Huang H,2014
93%
[80-98]
Nascimento-Carvalho C,2015
96.93%
[reference std:
RT-PCR]
Medjo B,2014
0.001
Gao J,2015
Not
significant
Hoshina T,2014
0.320
Elemraid M,2014
17
Neutrophil count : >10 × 109 /L
Bacterial vs viral pathogen
Prospective cohort
Neutrophil count : abnormal
Bacterial vs non-bacterial pathogen
Cohort
Neutrophil to lymphocyte ratio : 2.7
Bacterial vs viral pathogen
Retrospective cohort
CRP to mean platelet volume ratio : 11.0
Bacterial vs viral pathogen
Retrospective cohort
5.9
[1.47–23.94]
0.012
Elemraid M,2014
Not
significant
Hoshina T,2014
<0.001
Bekdas M,2014
<0.001
2. Clinically important endpoint: radiologic evidence of clinical suspicion of necrotizing pneumonia, multilobar
consolidation, lung abscess, pleural effusion, pneumothorax or pneumomediastinum
CONDITION
Necrotizing pneumonia
DIAGNOSTIC AID
Chest x-ray
Lung ultrasound
Lung ultrasound + CT scan
INCIDENCE
32/882 [3.7%]
10/140 [7.1%]
70/96 [72.1%]
AUTHOR / YEAR
Krenke K,2015
Lai S,2015
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.
SPECIMEN : FINDINGS
TECHNIQUE / STUDY DESIGN
YIELD
n/N [%, CI 95%]
PATHOGEN
REMARKS
AUTHOR/YEAR
CONTAMINANT
RESPIRATORY SECRETIONS
Induced sputum : +bacteria, Mycoplasma, virus
Culture, RT-PCR / Prospective cohort
Sputum : +bacteria
Culture / Prospective cohort
Nasopharyngeal aspirate : +Mycoplasma p
RT-PCR / Cross-sectional
Nasopharyngeal aspirate : +Mycoplasma p
Loop-med isothermal amp ass / Cross-sectional
Nasopharyngeal aspirate : bacteria, virus
Multiplex PCR,Quick Ag,culture / Cross-sectional
Lung aspirate and pleural fluid : bacterial
Culture / Cross-sectional
69/76
[91%]
138/464
[29.7%]
24/166
[14.5%]
38/368
[10.3%]
38/45
[84.4%]
20/57
[38%]
Pleural fluid : +bacteria
Culture / Retrospective cohort
Pleural fluid : +bacteremia
Culture / Cross-sectional
79/288
[27.4%]
2/5
[40.0%]
Honkinen M,2012
Vong S,2013
Medjo B,2014
Gotoh K,2012
Chen Y,2012
Howie S,2014
PLEURAL FLUID
Deceuninck G, 2013
Heine D,2013
BLOOD
Blood : +bacteremia
Culture / Meta-analysis
[5.14%,3.61-7.28%]
Blood : +bacteremia
27/862
Culture / Prospective cohort
[3.1%]
Blood : +bacteremia
18/405
Culture / Prospective cohort
[4.4%]
Blood : +bacteremia
0/45
Culture / Prospective cohort
Blood : +bacteremia
2/171
Culture / Prospective cohort
[1.2%]
Blood : +bacteremia
2/139
Culture / Retrospective cohort
[1.4%]
Blood : +bacteremia
26/369
Culture / Retrospective cohort
[7%, 4.7–10.1%]
Blood : +bacteremia
53/288
Culture / Retrospective cohort
[18.4%]
Blood : +bacteremia
6/390
Culture / Retrospective cohort
[1.5%]
Blood : +bacteremia
5/155
Culture / Cross-sectional
[3.2%]
Blood : +bacteremia
17/329
Culture / Cross-sectional
[5.1%]
Blood : +bacteremia
2/82
Culture / Case control
[2.4%]
Blood : +Pneumococcal bacteremia
1/73
Culture / Case control
[1.4%]
Blood : +Pneumococcal bacteremia
67/73
PCR for Streptococcus pneumoniae / Case control
[91.8%]
[14.7%]
CAP: severe vs
less severe [p=.008]
Iroh Tam P,2015
Vong S,2013
22/405
[5%]
Chisti M ,2014
Chen Y,2012
3/171
[1.8%]
3/139
[2.1%]
7/369
[1.8%]
Lai E,2014
Parikh K,2014
Myers A,2013
With empyema
thoracis
9/390
[2.3%]
1/155
[<1% ]
16/329
[4.9%]
Deceuninck G,2013
McCulloh R,2015
Heine D,2013
Real-time PCR
from dried blood spot
Selva A,2013
Ybanez S,2014
Complicated pneumococcal CAP vs control
(p=0.02)
Esposito S,2012
18
4. Clinically important endpoint: number of cases with metabolic derangement
DIAGNOSTIC AID : FINDINGS
STUDY DESIGN
n/N [%]
REMARKS
AUTHOR/YEAR
Blood pH : metabolic acidosis [total serum CO2 <17 mMol/L]
Case control
Blood pH : metabolic acidosis [pH<7.0,HC03<24 mM, anion gap>16 mM]
Case control
Serum sodium : soidum <130 mm/L
Cross-sectional
Serum sodium : soidum <130 mm/L
Cross-sectional
Serum potassium : potassium <3.5 mMol/L
Prospective cohort
66/164
[40.2%]
Total number of
cases: 21
Total number of
cases: 54
104/312
[33.3%]
51/180
[31%]
Diarrhea as
comorbid illness
Chisti M,2012
Wang L, 2013
Consolidation by
chest xray
Glatstein M,2014
Wrotek A,2013
Diarrhea as
comorbid illnes
Chisti M,2013
5. Clinically important endpoint: predictor of clinical outcome.
DIAGNOSTIC AID : FINDINGS
STUDY DESIGN
Blood pH : metabolic acidosis
[total serum CO2<17 mMol/L]
Case control
Blood pH : metabolic acidosis
[pH<7.0,HC03<24 mM, anion gap>16mM]
Case control
Chest x-ray : bilateral multilobar infiltrates
Retrospective cohort
Chest x-ray : unilateral multilobar infiltrates
Retrospective cohort
Chest x-ray : moderate to large effusion
Retrospective cohort
Chest x-ray : pleural effusion
Prospective cohort
Chest x-ray : consolidation
Prospective cohort
Pulse oximetry : O2 sat<90% at room air
Case control
Pulse oximetry : O2 sat <90% at room air
Prospective cohort
White blood cell count : >17,500/mL
Prospective cohort
White blood cell count : <4000
Case control
Blood culture : +bacteremia
Case control
Hemoglobin : <10 g/dL
Prospective cohort
Capillary blood glucose : <60 mg/dL
Case control
C-Reactive protein : >40 mg/L
Prospective cohort
Serum sodium : hyponatremia
Retrospective cohort
CRP : 7.5 mg/dL [median value]
Retrospective cohort
Lung ultrasonography : impaired perfusion,
hypoechoic lesions with effusion
Retrospective cohort
CLINICAL
OUTCOME
RR or OR
[95% CI]
Case fatality rate:
16% vs 5%
Comorbidity : diarrhea
Mortality
8.50
[2.82-25.60]
ICU
admission
Mechanical
ventilation
ICU
admission
Mechanical
ventilation
Initial
treatment
failure
6.6
[2.1-14.5]
3.0
[1.2-7.9]
8.0
[2.9, 22.2]
3.2
[1.1, 8.9]
14.8
[9.8-22.4]
14.10
[1.37-145.2]
0.56
[0.46-0.69]
2.40
[0.80-8.52]
1.91
[1.33-2.74]
2.42
[1.08-5.45]
1.77
[0.6-5.7]
7.39
[2.44-22.43]
2.38
[1.00-5.67]
1.33
[0.48-5.29]
1.01
[0.84-1.21]
Prolonged
hospitalization
Pneumatocoele
risk
Pneumatocoele
with subsequent
surgery
REMARKS
1.03
[1.00-1.04]
3.08
[1.15–8.29]
10.11
[2.95–34.64]
P
AUTHOR/YEAR
VALUE
0.039
Chisti M,2012
0.001
Wang L,2013
McClain L,2014
0.03
Huang C,2013
<0.001
Basnet S,2015
0.03
Jain D,2013
<0.001
Basnet S,2015
0.03
Huang C,2013
0.06
Jain D,2013
0.02
0.05
Huang C,2013
0.14
Jain D,2013
0.918
Basnet S,2015
10.01
Wrotek A,2013
Williams D,2015
Lai S,2015
8.28
[1.86–36.93]
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].
2016 KEY RECOMMENDATIONS**
1. For pCAP C, empiric antibiotic may be started if any of the following is present.
1.1. Elevated
1.2.1. serum C-reactive protein [CRP] [Recommendation Grade B1]
1.2.2. serum procalcitonin level [PCT] [Recommendation Grade B1]
1.2.3. white blood cell [WBC] count [Recommendation Grade B2] greater than 15,000 [Recommendation D]
1.2.4. lipocalin 2 [Lpc-2] [Recommendation Grade B2]
1.2 Alveolar consolidation on chest x-ray [Recommendation Grade B2]
1.3. Persistent high-grade fever without wheeze [Recommendation Grade D]
2. For pCAP D, a specialist may 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 OF
PATHOGENS1 REQUIRING
INITIAL ANTIBIOTIC
THERAPY
n/N [%]
POSITIVE YIELD
OF
VIRAL PATHOGEN
n/N [%]
0-16y
0-1y
1-4y
4-6y
6-16y
Adolescent
Child
806/3181 [25%]
716/1249 [57%]
451/1249 [37%]
42/1249 [3%]
40/1249 [3%]
2375/3181 [75%]
1440/2375 [67%]
744/2375 [31%]
92/2375 [4%]
99/237[4%]
83/190 [34%]
107/190 [56%]
1613/1613 [100%]
Child
678/1613 [42%]
935/1613 [58%]2
1802/2222 [81%]
<18y
330/1802 [18%]
1472/1802 [82%]
138/1691 [8%]
<5y
102/138 [74%]
126/138 [91%]
214/401 [53%]
<16y
132/214 [62%]
82/214 [38%]
279/2345
India
<12y
251/279 [90%]
Molecular
[12%]
4.7y
74/76
Finland
69 /74 [91%]
SD +1.9y
Culture, molecular
[97%]
503/722
Nepal
290/503 [58%]
<5y
Culture
[70%]
Taiwan
Culture, urine ag test,
209/245
7m-16y
123/209 [59%]
serology, virus isolation,
[85%]
immunofluorescence
1
Bacterial or codetection of bacterial and viral pathogens
2
RSV
28/279 [10%]
COUNTRY
LABORATORY METHOD
China
Culture, molecular
Austria
Culture, molecular
China
Culture
United States
Culture, serology
Niger
Molecular
UK
Culture, molecular,
urine ag test, serology,
immunofluorescence
POSITIVE YIELD [n]
PER SAMPLE
[or SUBJECT] [N]
n/N [%]
1381/3181
190/279 [68%]
AGE
AUTHOR
YEAR
Wei L
2015
Kurz H
2013
Peng Y
2015
Jain S
2015
Lagare A
2015
Elemraid M
2013
55/74 [72%]
213/503 [42%]
Mathew J
2015
Honkinen M
2012
Banstola A
2013
Chen C
2012
86/209 [41%]
2. Clinically important endpoint at site-of-care: surrogate markers of bacterial pathogen
2.1. Ambulatory patients
Gap in knowledge. No published data are available for review.
2.2. Hospitalized patients
Gap in knowledge in local literature. No data are available for review.
DIAGNOSTIC AID : FINDINGS
PATHOGEN
STUDY DESIGN
C-reactive protein [CRP] : >80 mg/L
Bacterial/atypical vs viral pathogen
Prospective cohort
C-reactive protein : elevated
Pneumococcal vs viral pathogen
Prospective cohort
C-reactive protein : elevated
Bacterial vs viral pathogen
Retrospective cohort
C-reactive protein : abnormal
Mycoplasma p vs non-Mycoplasma p
Cross-sectional
C-reactive protein : > 200 ug/ml
Bacterial pathogen
Case control
Procalcitonin : elevated
Bacterial vs non-bacterial pathogen
Prospective cohort
ODDS RATIO
[95% CI]
YIELD
[%]
3.6
[1.65–8.07]
p VALUE
SPECIFICITY
[95% CI]
Elemraid M
2014
0.001
19
[ 5-75]
Galetto-Lacour A
2013
30.9 vs 23.7
0.020
Hoshina T
2014
0.002
Gao J
2015
56.10%
23
[5-117]
AUTHOR
YEAR
Huang H
2014
Galetto-Lacour A
2013
21
Procalcitonin : elevated
Pneumococcal vs non-bacterial pathoge
Retrospective cohort
Lipocalin 2 : >130,1
Probable bacterial pathogen
Case control
Chest x-ray : presence of pneumonia
Pneumococcal infection
Cross-sectional
White blood cell count : abnormal
Mycoplasma p vs non-Mycoplasma p
Cross sectional
White blood cell count : abnormal
Bacterial vs non-bacterial pathogen
Cohort
White blood cell count : >15 × 109/L
Bacterial vs viral pathogen
Prospective cohort
109/L
Hoshina T
2014
0.0008
65.5%
vs
55.2%
0.5
[0.13–1.96]
Neutrophil count : >10 ×
5.9
Bacterial vs viral pathogen
[1.47–23.94]
Prospective cohort
Neutrophil count : abnormal
Bacterial vs nonbacterial pathogen
Cohort
Neutrophil to lymphocyte ratio : 2.7
Bacterial vs viral pathogen
Retrospective cohort
CRP to mean platelet volume ratio: 11.0
Bacterial vs viral pathogen
Retrospective cohort
85.7%
Huang H
2014
93%
[80-98%]
Nascimento-Carvalho C
2015
0.001
Gao J
2015
Not
significant
Hoshina T
2014
0.320
Elemraid M
2014
0.012
Not
significant
<0.001
Hoshina T
2014
Bekdas M
2014
<0.001
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].
2016 KEY RECOMMENDATIONS**
1. For a patient who has been classified as pCAP A or pCAP B without previous antibiotic, regardless of the
immunization status against Haemophilus influenzae type b or Streptococcus pneumoniae,
1.1. Amoxicillin trihydrate may be given [Recommendation Grade B1].
1.1.1. It may be given at 40-50 mg/kg/day, maximum dose of 1500 mg/day in 3 divided doses in
areas with proven low antibiotic resistance to amoxicillin [Recommendation Grade D].
1.1.2. It may be given at 90 mg/kg/day in areas with proven high amoxicillin resistance
[Recommendation Grade D].
1.1.3. It may be given for a minimum of 3 days [Recommendation Grade B2].
1.1.4. It may be given in 2 divided doses for a minimum of 5 days [Recommendation Grade B2].
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 day 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 if there is
1.2.1. known hypersensitivity to amoxicillin [Recommendation Grade D].
1.2.2. suspicion of atypical organisms particularly Mycoplasma pneumoniae [Recommendation Grade D].
2. For a patient who has been classified as pCAP C without previous antibiotic and
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] may be given [Recommendation Grade B2].
*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
AGE
METHOD
STUDY DESIGN
Latin America
and
Carribean
Culture, PCR
Meta-analysis
Streptococcus
+YIELD pneumoniae
%
% [95%
CI]
OTHER BACTERIA
% [95%
CI]
ATYPICAL ORGANISM
%
[95% CI]
Haemophilus influenzae: 3.64% [1.62–6.42] Mycoplasma pneumoniae
3.56% [0.99–7.64]
Staphylococcus aureus: 3.44% [2.08–5.11] Chlamydia trachomatis
2.97% [0.74–6.60]
Haemophilus influenzae b:3.08%[1.21–5.79]
Chlamydia
pneumoniae
Streptococcus pyogenes: 1.54%[0.49–3.15]
2.60% [0.22–7.46]
Haemophilus influenzae: 38.0%
Klebsiella pneumoniae: 14.3%
Pseudomonas aeruginosa:12.3%
Not determined
Bordetella pseudomallei:
9.3%
Staphylococcus aureus:
3.7%
Mycobacterium sp:
15.7%
AUTHOR
YEAR
<5y
30.6%
11.08%
[7.63 -15.08]
Cambodia
Culture
Cross-sectional
>5y
89.0%
17.7%
China
Culture
Cross-sectional
Child
50.2%
29.7%
Hemophilus influenzae:
Moraxella catarrhalis:
40.8%
7.3%
Mycoplasma pneumoniae
29.82%
91%
50%
Hemophilus Influenzae:
Moraxelle catarrhalis:
Staphylococcus aureus:
38.0%
28.0%
13.0%
Mycoplasma pneumoniae Honkinen M
2012
3.0%
Finland
6m-15y
Culture
Cross-sectional
Gentile A
2012
Vong S
2015
Peng Y
2015
1.2. Pattern of antibiotic resistance among antibiotic-requiring pathogens in hospitalized patients
2012-2015 local hospital data reported by Antimicrobial Resistance Surveillance Program showed the
following antimicrobial resistance rates [Antimicrobial Resistance Surveilance Reference Laboratory, Antimicrobial
Resistance Surveilance Program 2012, 2013, 2014, 2015 Annual Reports].
1.21. Streptococcus pneumoniae
Penicillin
Chloramphenicol
Cotrimoxazole
Erythromycin
Azithromycin
Sulbactam-ampicillin
Ceftriaxone
Levofloxacin
1.2.2. Haemophilus influenzae
Chloramphenicol
Cotrimoxazole
Ampicillin
Amox/clavulanic
Sulbactam-ampicilin
2012
2013
2014
2015
8.0%
8.7%
22.4%
4.3%
0%
6.7%
-
5.0%
3.0%
20.0%
6.0%
0%
2.0%
7.0%
4.0%
17.3%
4.3 %
-
7.6%
2.6%
16.5%
5.0%
0%
-
2012
2013
2014
2015
13.4%
42.9%
12.0%
4.1%
-
5.7%
32.5%
8.9%
5.2%
3.4%
8.2%
7.0%
34.1% 34.0%
16.7% 17.0%
7.0%
24
1.2.3. Staphylococcus aureus
2012
2013
2014
2015
95.0%
53.0%
1.0%
12.0%
15.0%
1.0%
8.0%
14.0%
2.0%
95.5%
60.3%
0.9%
11.0%
12.0%
4.1%
7.4%
22.0%
1.2%
96.0%
62.6%
0.7%
10.4%
11.0%
4.9%
4.9%
25.9%
1.7%
2013
2014
2015
7.7%
4.0%
0%
1.0%
13.4% 12.0%
15.0%
7.5%
7.0%
14.7% 18.0%
3.5%
1.0%
6.0%
1.0%
14.%
16.%
10.%
26.%
1.7%
6.9%
0.9%
14.0%
14.0%
6.2%
29.0%
2.2%
Penicillin
95.4%
Oxacillin
54.9%
Vancomycin
0%
Clindamycin
8.4%
Erythromycin
10.9%
Rifampin
Ciprofloxacin
Cotrimoxazole
9.3%
Linezolid
1.6%
1.2.4. Methicillin-resistant Staphylococcus aureus
2012
Rifampin
Vancomycin
Clindamycin
Erythromycin
Ciprofloxacin
Cotrimoxazole
Linezolid
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
STUDY DESIGN
AGE
INTERVENTION
Azithromycin
vs erythromycin
Clarithromycin
vs erythromycin
Azithromycin
vs co-amoxiclav
Subgroup in
meta-analysis
<18y
Cohort
1-18y
Co-amoxiclav
vs amoxicillin
NUMBER
OF
SUBJECTS
233 vs 133
Cure rate
236 vs 156 Failure rate
84 vs 69
Side effects
124 vs 110
Cure rate
124 vs 110 Failure rate
121 vs 105 Relapse rate
133 vs 127 Adverse event
125 vs 63
Cure rate
164 vs 112 Failure rate
164 vs 112 Side effect
50 vs 50
Cure rate
50 vs 50
Side effect
948 vs 839 Failure rate
nonsevere CAP
203 vs 99
Amoxicillin
42 vs 42
vs cefuroxime
Amoxicillin
923 vs 142
vs chloramphenicol
Cotrimoxazole
55 vs 56
vs chloramphenicol
Amoxicillin
42 vs 40
vs clarithomycin
42 vs 40
Cefuroxime
vs clarithromycin
B-lactam monotherapy
1164
vs macrolide
RCT
6-59m
Amoxicillin 5d vs 10d
80 mkd
given TID 3d vs 10d
RCT
11-59m
Amoxcillin
50 mkd
BID
3d vs
5d vs 7d
CLINICALLY
IMPORTANT
ENDPOINT
RISK or ODDS RATIO
[95% CI]
REMARKS
Risk classification scheme: pCAP A or B
1.22 [0.50-2.94]
0.73 [0.18-2.89]
0.92 [0.18-4.73]
1.61 [0.86-3.08]
0.52 [0.12-2.23]
0.17 [0.02-1.45]
1.07 [0.60-1,90]
1.02 [0.54-1.95]
1.21 [0.42-2.53]
0.15 [0.04-0.61]
10.44 [2.85-38.21]
5.21 [0.24-111.24]
1.18 [0.91-1.51]
Failure rate
1.71 [0.94-3.11]
Cure rate
2.05 [0.18-23.51]
Failure rate
0.64 [0.41-1]
Cure rate
1.06 [0.47-2.40]
Cure rate
1.05 [0.06-17.40]
Cure rate
0.51 [0.04-5.89]
severe CAP
p VALUE
Treatment
failure
Not
significant
Failure rate
p=0.16
Failure rate
Lodha R
2013
Ambroggio
L 2015
40% vs 0%
0% vs 0%
143
AUTHOR
YEAR
12.5% vs
15.0% vs 0%
Greenberg
D 2014
Florendo S
2012
25
Risk classification scheme: pCAP C
Amoxicillin
vs procaine penicillin
Cotrimozaxole
vs procaine penicillin
Cotrimozaxole
vs penicillin+ampicillin
Chloramphenicol
vs penicillin+gentamycin
Chloramphenicol+ampicillin
vs gentamycin
Subgroup
in metaanalysis
<18y
Chloramphenicol+penicillin
vs ceftriaxone
Ampicillin
vs penicillin+chloramphenicol
Benzathine penicillin
vs procaine penicillin
Penicillin+gentamycin
vs co-amoxiclav
Co-amoxiclav
vs oxacillin+ceftriaxone
Oral vs parenteral antibiotic
for severe pneumonia
68 vs 86
Failure rate
0.75 [0.17-3.25]
349 vs 374
303 vs 311
66 vs 68
Cure rate
Failure rate
Cure rate
1.58 [0.26-9.69]
1.72 [0.41-7.27]
1.15 [0.36-3.61]
559 vs 557
559 vs 557
479 vs 47
Adverse events
Readmission < d 30
Failure rate day 5
1.26 [0.96-1.66]
1.61 [1.02-2.55]
1.51 [1.04-2.19]
46 vs 51
Cure rate
1.36 [0.47-3.93]
52 vs 49
Cure rate
0.48 [0.15-15.1]
135 vs 146
Cure rate
0.43 [0.27-1.01]
38 vs 33
55 vs 56
8/56 vs 7.48
Failure rate
Relapse rate
Failure rate
0.86 [0.05-14.39]
1.02 [0.24-4.30]
0.98 [0.93-2.92]
1982 vs 1960
1948 vs 1922
1048 vs 1028
236 vs 256
Failure rate day 3
Failure rate <5y
Relapse rate
Readmission within
7 days
ICU admission
0.95 [0.78-1.15]
0.91 [0.76-1.09]
1.28 [0.34-4.82]
Cohort
2m-18y
Cohort
<5y
RCT
3m-2y
Broad vs narrow
spectrum antiobiotic
Broad vs narrow
spectrum antibiotic
Ampicillin or penicillin
vs cefuroxime
Metaanalysis
3-59 m
Amoxicillin
vs standard IV antibiotic
12364
subjects
Treatment failure
nd
2 day
Treatment failure
6th day
0.82 [0.55-0.82]
Metaanalysis
<18y
Amoxicillin
vs procaine penicillin
68 vs 86
Failure rate
0.75 [0.17-3.25]
Cohort
2m-11y
RCT
3-59m
Penicillin G q 4 vs q6
120 vs 144
Final outcome
Amoxicillin given at home
then hosp vs at hosp alone
68 vs 86
Treatment failure
13954 vs
1610
66 vs 253
0.25
Treatment failure
Dinur-Schejter Y
7.6%
2013
vs 4.7%
HR
1.79 [1.30-2.46]
Pneumonia-related
readmission <30 days
2489 vs
18254
Readmission
RCT
3m–15y
Penicillin G
vs IV cefuroxime
58 children
Clinical course
RCT
<2y
Amoxicillin
vs benzyl penicillin
Treatment failure
< 0.01
0.71
[Age:1-4y]
0.14
[Age:5–17y]
0.30
[Age:1-4y]
0.58
[Age:5–17y]
0.10 [Age:
1-4y]
0.58
[Age:5–17y]
0.96
[Age:1-4y]
0.37
[Age:5–17y
All-cause
readmission
<30 days
Β-lactam+macrolide
vs B-lactam monotherapy
Lodha R
2013
No diffeference
4701 vs 8892
Cohort
1-18y
Das R
2013
0.92 [0.76-1.10]
Mortality
Ceftriaxone
vs ceftriaxone+macrolide
Queen M
2014
Wlliams D
2013
0.85 [0.27 -2.73]
Transfer to ICU
> 2nd day
Cohort
1-17y
Lodha R
2013
Brandao A
2014
Patel A
2015
Leyenaar J
2014
0.69 (0.41-1.12)
Ambroggio L
2013
Not
significant
Amarilyo G
2014
7.7%
vs
8.0%
[per
Agwayu A
2015
protocol
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].
2016 KEY RECOMMENDATIONS**
1. For pCAP A, B, C or D in which a non-influenza virus is the suspected pathogen, antiviral drug therapy
may not be beneficial [Recommendation Grade D].
2. For pCAP C or D, antiviral drug therapy for clinically suspected or laboratory-confirmed influenza virus to
reduce
2.1. risk of pneumonia may not be beneficial [Recommendation Grade B1].
2.2. time to symptom resolution may be beneficial [Recommendation Grade B1].
2.2.1. 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 <15 kg at
30 mg twice daily x 5 days, >15-23 kg at 45 mg twice daily x 5 days, >23-40 kg at 60 mg twice daily
x 5 days, >40 kg at 75 mg twice daily x 5 days; doses to be started within 48 hours of onset of
influenza-like symptoms.
2.2.2. zanamivir [for children >7 years old at 10 mg (two 5-mg inhalations) twice daily x 5 days,
within 36 hours of onset of influenza-like symptoms.
3. Oseltamivir or zanamivir may be benefical to reduce the burden of pneumonia during a flu epidemic
[Recommendation Grade C1].
4. Symptomatic and ancillary treatment may be beneficial [Recommendation Grade D].
nd
*Grading of recommendation in the 2012 PAPP 2 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.
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
SITE
VIRAL ISOLATE
<1y old
Total
Cordillera
Administrative
Region
Tacloban
RSV
Flu B
Flu A
Flu A [H1N1]
Total
Rhinovirus
RSV
Adenovirus
Flu A
60.3%
1.9%
0.94%
1.9%
RATE
%
1-4y old
28.1% [106/377]
26.4%
2.8%
2.8%
0
61.2% [501/819]
30.5%
24.1%
4.0%
2.2%
AUTHOR
YEAR
>5y old
Perez C
2012
0.94%
0.94%
0
0
Suzuki A
2012
1.2. Global data
INCIDENCE
STUDY DESCRIPTION
Data: worldwide from Apr 2000-Aug 2014
Study design: meta-analysis [21 studies, 10196 subjects].
PCR based
Europe [12 countries]
AREA
Asia [5 countries]
Other areas [4 countries]
≤1 y old
AGE
2–5 y old
≥6 y old
Rhinovirus
RSV
Bocavirus
VIRAL
Parainfluenza
ISOLATE
Influenza
hMetapneumovirus
Adenovirus
Coronavirus
POOLED %[CI 95%]
57.4 [50.8–64.1]
2
MIXED % [CI 95%]
I2
97.9
29.3 [22.4–36.2]
96.1
I
61.7 [50.–70.3]
58.0 [47.1–68.8]
44.2 [34.6–53.8]
76.1 [62.8–89.4] 95.1
63.1 [50.2–75.9] 94.1
27.9 [4.3–51.5] 96.3
18.9 [14.3–23.4]
17.5 [13.3–21.6]
12.7 [8.5–16.9]
7.8 [6.0–9.5]
6.3 [4.7–8.0]
6.1[ 4.1–8.1]
6.0 [4.4–7.7]
3.9 [2.1–5.7]
AUTHOR
YEAR
33.8 [18.0–49.5]
23.7 [15.8–31.5]
29.3 [23.0–35.6]
Wang M
2015
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
STUDY DESIGN
SUBGROUP
ODDS or RISK RATIO MEAN DIFFERENCE AUTHOR
ENDPOINT
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
2 studies
Serious adverse event
1.97 [0.59-6.56 ]
Meta-analysis
Jefferson T
2 studies
Vomiting
1.70 [1.23-2.35 ]
2014
Zanamivir
2 studies
Risk for pneumonia
0.53 [0.12-2.38]
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.
3. For ancillary treatment, please see Clinical Question 11.
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].
2016 KEY RECOMMENDATIONS**
1. Good clinical response to current therapeutic management may be assessed based on achieving clinical
stability that is sustained for the immediate past 24 hours [Recommendation Grade D].
1.1. For pCAP A or B, clinical stability may be assessed within 24-48 hours after consultation if
cough has improved or body temperature in Celsius has returned to normal [Recommendation Grade D].
1.2. For pCAP C, clinical stability may be assessed within 24-48 hours after admission [Recommendation
Grade C1] if any of the following physiologic parameters has significantly improved or returned to normal.
1.2.1. Respiratory rate [Recommendation Grade C1] at full minute based on the WHO-defined, age-specific
values for tachypnea [Recommendation Grade D].
1.2.2. Oxygen saturation at room air using pulse oximetry [Recommendation Grade C1].
1.2.3. Body temperature in Celsius [Recommendation Grade C1].
1.2.4. Cardiac rate at full minute based on Pediatric Advanced Life Support age-based values
[Recommendation Grade C2].
1.2.5. Work of breathing [Recommendation Grade D].
1.3. For pCAP D, clinical stability may be assessed within 48-72 hours after admission if all of the
following physiologic parameters have significantly improved: respiratory rate at full minute based on
the WHO-defined, age-specific values for tachypnea, oxygen saturation using pulse oximetry, body
temperature in Celsius, cardiac rate at full minute based on Pediatric Advanced Life Support agebased values, and work of breathing [Recommendation Grade D].
2. Good clinical response to current therapeutic management may not require chest x-ray or complete blood
count to document treatment success at end of treatment [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.
2. Physiologic endpoints in monitoring for clinical stability
STUDY DESIGN
PHYSIOLOGIC ENDPOINT
N
STABILITY
DEFINITION
Cohort
TIME TO RESOLUTION
Median (IQR) in hours, CI 95%]
N
<2y
2-4y
5-17
130
90
101
101
21
97
90
61
73
63
58
63
62
62
61
108
72
109
AGE
<2y
AUTHOR
YEAR
2-4y
5-17
14.5 (4.5-45.3)
4.5 (0.3-18.4)
38.6 (18.7-68.9)
39.5 (19.2-73.6)
18.4 (2.8-42.8)
21.8 (5.7,-1.9)
31.6 (9.5-61.9)
44.2 (24-77.6)
10.6 (0.8-34)
18 (5.8-42.2)
24.3 (10.8-59.2)
38.3 (18-70.6)
69
40.5 (20.1-75.0)
39.6 (15.6-79.2)
30.4 (14.7-59.2)
73
68
40.2 (19.5-73.9)
35.9 (15.9-77.6)
29.8 (17.2-56.6)
110
77
73
40.5 (20.7-70.1)
39.1 (18.4-77.6)
28.2 (14.7-44.7)
110
72
71
40.5 (20.7-70.1)
39.7 (20.1-77.5)
29.2 (18.2-54)
Single endpoint
1. Fever
2. Tachycardia
3. Tachypnea
4; Needing O2 support
Multiple endpoints
1
Temp: 36.0-37.9
1
Normal
334
1. Tachypnea
+ needing O2 support
2. Tachypnea + tachycardia
+ needing O2 support
3. Tachypnea + fever
+ needing O2 support
4.Tachypnea + tachycardia
+ fever + needing O2 support
None
Normal RR
None
Normal RR,HR
None
Normal RR, none
None
Normal RR,HR
None
Wolf R
2015
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.
STUDY DESIGN
PHYSIOLOGIC ENDPOINT
Cohort
Single endpoint
1
1. Tachypnea
2. Fever
3. O2 sat <92%
N
N
STABILITY
DEFINITION
<1y
2174
1
Normal
Normal
Normal
TIME TO
RESOLUTION
Median
[50th percentile]
In hours
>1y
1703 1011
629
192
<1y
>1y
22
48
12
10
NUMBER OF SUBJECTS WITH
PERSISTENT ABNORMALITY
BEYOND 48 HOURS
DAY OF
OPD VISIT
DISCHARGE
AT DAY 14
AGE
<1y
>1y
<1y
>1y
135
381
15
31
11
AUTHOR
YEAR
Izadnegahdar R
2012
70
0
0
Based on data from Fleming S: Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a
systematic review of observational studies. Lancet 2011; 377:1011–1018.
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]
2016 KEY RECOMMENDATIONS**
1. If a patient classified as either pCAP A or pCAP B is not improving, or clinically worsening, within 72 hours
after initiating a therapeutic intervention [treatment failure], diagnostic evaluation to determine if any of
the following is present may be considered [Recommendation Grade D].
1.1. Coexisting or other etiologic agents
1.2. Etiologic agent resistant to current antibiotic, if being given
1.3. Other diagnosis
1.3.1. Pneumonia-related complication
1.3.1.1. Necrotizing pneumonia
1.3.1.2. Pleural effusion
1.3.2. Asthma
1.3.3. Pulmonary tuberculosis
2. If a patient below 5 years of age [Recommendation Grade B1], and 5 years old or more [Recommendation Grade D]
classified as pCAP C is not improving, or clinically worsening, within 48 hours after initiating a therapeutic
intervention [treatment failure], diagnostic evaluation to determine if any of the following is present may be
considered.
2.1. Coexisting or other etiologic agents [Recommendation Grade C1]
2.2. Etiologic agent resistant to current antibiotic, if being given [Recommendation Grade D]
2.3. Other diagnosis
2.3.1. Pneumonia-related complication [Recommendation Grade B2]
2.3.1.1. Acute respiratory failure
2.3.1.2. Pleural effusion
2.3.1.3. Pneumothorax
2.3.1.4. Necrotizing pneumonia
2.3.1.5. Lung abscess
2.3.2. Asthma [Recommendation Grade D].
2.3.3. Pulmonary tuberculosis [Recommendation Grade D]
2.3.4. Sepsis [Recommendation Grade C2]
3. If a patient classified as pCAP D is clinically worsening within 24 hours after initiating a therapeutic
intervention, referral to a specialist may 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
STUDY DESIGN
AGE GROUP
Kenya
Cohort
2-59m
Nepal
Cohort
2-35m
Kenya
Cohort
2-59m
India
Case control
3-59m
1
n/N
RATE
[95% CI]
AUTHOR
YEAR
3/169
1.8%
[0.4–5.1]
Agweyu A
2014
42/453
12%
Webb C
2012
209/610
35%
Basnet S
2015
43/201
21.4%
[15.9–27]
Agweyu A
2014
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
2. No improvement in any these clinical abnormalities; or
3. New findings of empyema, bacterial meningitis, signs of shock or renal impairment
(creatinine >100 mmol/L)
69/165
32%
Webb C
2012
pCAP C [or SEVERE PNEUMONIA] and pCAP D [or VERY SEVERE PNEUMONIA]
1. No improvement or worsening of tachypnea or lower chest indrawing; or
2. New appearance, no improvement or worsening of danger signs such as inability to drink, abnormal
sleepiness, difficult to awake from sleep, stridor in a calm child, central cyanosis, and convulsions; or
3. Occurrence of empyema, pneumothorax, lung abscess, meningitis, septicaemia, shock, respiratory
failure)
37/181
20.4%
Jain D
2013
DESCRIPTION OF TREATMENT FAILURE
pCAP C [or SEVERE PNEUMONIA]
1. Development of signs of very severe pneumonia at any time, or
2. Absence of improvement of ALL of the following: indrawing (persistence), measured temperature
reduction of ≥0.5 °C and respiratory rate (reduction of ≥5 bpm), or
3. Identification of pathogen with in vitro resistance to antibiotics at any time point
1. Worsening, compared to admission findings, of one or more of these clinical abnomalities: conscious
level, SaO2 <90%; RR (must have increased by at least 5 breaths/min), or temp (if initially<37.5°C,
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)
Failure to improve1 AND 1. a requirement for a change in antibiotics to second line therapy; or
2. development of empyema or pneumothorax requiring surgical intervention; or
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
3. Absence of improvement of ALL of the following: indrawing (persistence), measured temperature reduction of ≥0.5°C, RR (reduction of ≥5 bpm), ability to drink AND requirement of supplementary O2; or
4. Identification of a pathogen on blood culture or from pleural fluid with in vitro resistance to antibiotics
at any time point.
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
AT LEAST 48 HOURS AFTER ADMISSION
Clinician’s decision to change treatment in absence of criteria
Persistence of tachypnea, fever and indrawing
Documented signs of deteriorating clinical status
Radiological findings informing change of treatment
Bacteriological findings informing change of treatment
Persistence of tachypnea or lower chest indrawing
Empyema / pneumothorax
Hypoxemia [SaO2 <90%]
Persistence or new appearance of danger signs
Meningitis
Lung abscess
Worsening conscious level
Worsening SaO2
Persistent SaO2 <90%
Worsening respiratory rate
Worsening temperature
Persistent lower chest wall indrawing
New bacterial meningitis
New renal impairment
New signs of shock
New empyema
Admission to the intensive care unit
Nasopharyngeal aspirate positive for human metapneumovirus
Nasopharyngeal aspirate positive for RSV
1
Odds to having treatment failure
n/N [RATE]
54/100 (54.0%)
25/100 (25.0%)
12/100 (12.0%)
2/100 (2.0%)
1/100 (1.0%)
10/31 (32.2%)
6/31 (19.3%)
7/31 (22.5%)
5/31 (16.1%)
2/31 (6.4%)
1/31 (3.2%)
48 hr after admission
5 days after admission
4 ( 3.6%)
3 ( 5.0%)
19 (17.0%)
2 ( 3.0%)
0
19 (31.0%)
61 (55.0%)
12 (19.0%)
22 (20.0%)
1 ( 2.0%)
0
31 (50.0%)
2 ( 1.8%)
2 ( 3.0%)
0
1 ( 2.0%)
3 ( 2.7%)
4 ( 6.0%)
0
0
7/209 (3.34%)
1
OR [95% CI]
p VALUE
2.34 (0.62- 8.81)
0.209
1.47 (0.91, 2.38)
0.115
AUTHOR
YEAR
Agweyu A
2014
Jain D
2013
Webb C
2012
Basnet S
2015
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].
2016 KEY RECOMMENDATIONS**
1. For pCAP C, switch from intravenous antibiotic administration to oral form may be beneficial to reduce length
of hospital stay [Recommendation Grade C1] provided all of the following are present [Recommendation Grade D].
1.1. Current parenteral antibiotic has been given for at least 24 hours
1.2. At least afebrile within the last 8 hours without current antipyretic drug
1.3. Responsive to current antibiotic therapy as defined in Clinical Question 8
1.4. Able to feed, and without vomiting or diarrhea
1.5. Without any current pulmonary [effusion / empyema, abscess, air leak, lobar consolidation or
necrotizing pneumonia] or extrapulmonary [meningitis or sepsis] complications
1.6. Oxygen saturation > 95% at room air
2. For pCAP D, referral to a specialist may be done if switch therapy is considered.
*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.
CAP SEVERITY
STUDY DESIGN
AGE GROUP
Severe CAP RCT,
non-inferiority
1-60m
RESULTS
CLINICALLY IMPORTANT ENDPOINT
Control group
n=31
Switch therapy group
n=26
AUTHOR
p
YEAR
VALUE
Mortality
0
0
Complications
0
0
-
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
In-iw S
2015
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].
2016 KEY RECOMMENDATIONS**
1. During the course of illness for pCAP A or pCAP B, the following
1.1. may be beneficial.
1.1.1. Oral steroid in a patient with coexisting asthma [Recommendation Grade D].
1.1.2. Bronchodilator in the presence of wheezing [Recommendation Grade D].
1.2. may not be beneficial.
1.2.1. Cough preparation [Recommendation Grade A1] or parenteral steroid in a patient without asthma
[Recommendation Grade B1].
1.2.2. Elemental zinc, vitamin D 3 and probiotic [Recommendation Grade D].
2. During the course of illness for pCAP C, the following
2.1. may be beneficial.
2.1.1. Use of either nasal catheter or nasal prong in administering oxygen [Recommendation Grade A1].
2.1.2. Zinc supplement in reducing mortality [Recommendation Grade B1].
2.1.3. Use of bubble CPAP instead of low flow oxygen in improving oxygenation [Recommendation Grade C2].
2.1.4. Steroid or spirulina in reducing length of stay [Recommendation Grade B2].
2.1.5. Oxygen for oxygen saturation below 95% at room air in improving oxygenation [Recommendation Grade D].
2.2. may not be beneficial.
2.2.1. Zinc supplement in reducing treatment failure or length of hospital stay [Recommendation Grade A1].
2.2.2. Vitamin D 3 in reducing length of hospital stay [Recommendation Grade A1].
2.2.3. Parenteral steroid, probiotic, virgin coconut oil, oral folate and nebulization using saline or
acetylcysteine [Recommendation Grade C2].
3. During the course of illness for pCAP D, referral to a specialist may be beneficial [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
1. Interventions that may be beneficial as an ancillary treatment
INTERVENTION
STUDY DESIGN
CLINICALLY
IMPORTANT ENDPOINT
RESULTS
RISK or ODDS
p
REMARKS
RATIO [95% CI] VALUE
AUTHOR
YEAR
Intervention of proven benefit in pCAP C to reduce mortality.
Zinc
RCT, double-blind, placebo-controlled
Case fatality
Srinivasan M
2012
0.33 [0.15-0.76]
Interventions of equal benefit in pCAP C to reduce treatment failure.
O2 delivery: bubble CPAP vs low flow O 2
RCT
Treatment failure
0.27 [0.77-0.99]
0.0026
Trial stopped
earlier
Interventions of equal benefit in pCAP C to achieve adequate oxygen saturation.
O2 delivery:nasal prong vs nasopharyngeal catheter
Meta-analysis
Failure to achieve
adequate SaO2
0.93 [0.36 -2.38]
Chisti M
2015
Reyes-Rojas M
2014
Interventions of potential benefit in pCAP C to reduce length of hospital stay and improve crackles score.
Steroid
RCT, double-blind, placebo-controlled
Spirulina
RCT, open label
Zinc
RCT
0.019
Justina M
2012
0.0006
Dioniso-Delfin T
2012
Guinto, M
2014
Length of stay
Crackles score
0.034
2. Interventions requiring more studies to assess benefit as an ancillary treatment
Cough preparation
Meta-analysis
Steroid
Retrospective cohort
Interventions in pCAP A or B.
Not improved
Treatment failure
2.38 [1.03-5.52]
0.04
Combined child
and adult
[-] asthma hx
1.12 [0.43-2.92]
0.80
[+] asthma hx
0.80 [0.38-1.67]
Chang CC
2014
Ambroggio L
2014
Interventions in pCAP C.
Steroid
RCT, double-blind, placebo-controlled
Chest physiotherapy
Meta-analysis
Vitamin D
Meta-analysis
Risk of readmission
Justina M
2012
Chaves G
2013
0.46
0.11-0.79
0.29
Length of stay
Pooled mean
diff: -5.75
[-11.54-0.04]
Zinc
Meta-analysis
0.88
[0.71-1.10]
1.3
[0.8-2.1]
Treatment failure
Macalino M
2013
Wadha N
2013
Sempe rtegu F
2012
1.00
[0.68-1.50]
Shah G
2012
0.423
Zinc
RCT, double-blind, placebo-controlled
Time to normalization of RR,
temperature
and SaO2
Length of stay
0.306
0.897
0.823
Srinivasan M
2012
0.05
Rulloda M
2012
Shah GS
2012
Fataki M
2014
Chisti M
2015
Vierneza M
2012
Becina P
2014
Villanueva J
2013
Mondragon A
2014
Martinez M
2012
Delizo M
2014
0.193
0.089
O2 delivery:bubble CPAP vs high flow O2
RCT, open label
Virgin coconut oil
RCT
Probiotic
RCT
Oral folate
RCT, placebo-controlled
Vitamin D3
RCT
Nebulization: acetylcysteine vs saline
RCT
Nebulization: saline or bronchodilator
Cross-sectional
Treatment failure
Das R
2013
Bernabe J
2012
0.50
[0.11-2.99]
Low
enrollment
Trial stopped
earlier
0.336
Mean:
3.2d vs 3.3d
Mean:
4.0d vs 4.8d
Length of stay
Not
significant
Mean:
2.5d vs 2.9d
Not
significant
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]
2016 KEY RECOMMENDATIONS**
1. The following are beneficial in reducing the burden of hospitalization because of pneumonia.
1.1. Conjugated vaccine [PCV 10 or 13] against Streptococcus pneumoniae [Recommendation Grade A1]
1.2. Vaccine against Haemophilus Influenzae type b [Recommendation Grade C1], Influenza sp
[Recommendation Grade C2 ] and Diphtheria, Pertussis, Rubeola and Varicella [Recommendation Grade D]
1.3. Breastfeeding [Recommendation Grade B1]
1.4. Avoidance of cigarette smoke [Recommendation Grade B1] and biomass fuel [Recommendation Grade C1]
2. The following are not beneficial in reducing the clinical impact of pneumonia.
2.1. Zinc supplement [Recommendation Grade A1]
2.2. Vitamin D [Recommendation Grade A2]
nd
*Grading of recommendation in the 2012 PAPP 2 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
1. Rationale for prevention: burden of illness
BURDEN
MORBIDITY
Acute lower respiratory
infection and pneumonia
Hosp for pneumonia
SITE
Nationwide
ICD code 10 18.0,18.9, 18.91,
18.92,18.93
MORTALITY
Pneumonia-related.
ICD code 10 J18.0,18.9, 18.91,
18.92,18.93
Pneumonia-related
6
ECONOMIC BURDEN
PNEUMONIA SEVERITY
Moderate risk
1
High risk
STUDY
PERIOD
AGE
GROUP
AVERAGE NUMBER
PER YEAR
2012-14
<5y
5-14y
286 073
326,326
2012-15
28d-19y
242,086
MEAN RATE
Department
1
of Health
2.26%
2000-13
<5y
STUDY PERIOD
AGE
GROUP
2012
Adult
Philippine
Pediatric
Society,Inc3
7.9% 2
Nationwide
Worldwide
SOURCE
0.935 [UR5 0.817-1.057]
Philippine
Pediatric
Society,Inc3
4
14.9% [UR5 13.0-16.8]
ESTIMATED TOTAL HEALTH CARE COST
PhP 8.48 billion
PhP 643.76 million
Liu L,2014
7
Mendoza B
2015
2012, 2013, and 2014 Annual Reports Field Health Services Information System Department of Health.
Rate = discharges due to pneumonia / total number of discharges from Jan 1, 2012 to December 31, 2015.
ICD 10 Registry, Committee on Registry of Childhood Disease, Philippine Pediatric Society, Inc.
4
Rate = deaths due to pneumonia / total number of discharges due to pneumonia from Jan 1, 2012 to December 31, 2015.
5
UR – uncertainty range
6
Gap in knowledge: no available data exclusive for children.
7
Estimated mean value based on Philippine Health Insurance claims and estimated healthcare cost.
2
3
36
2. Interventions that may be beneficial to prevent pneumonia, or reduce pneumonia-related morbidity
and mortality
INTERVENTION
STUDY DESIGN
COUNTRY
AGE
USA
<18y
PCV 13
Time-trend analysis
Uruguay
<14y
Argentina
PCV 13
Cohort
<5y
Alaska
<5y
USA
<2y
CLINICALLY
RESULTS
IMPORTANT
RISK, HAZARD or ODDS
REMARKS
ENDPOINT
RATIO [95% CI]
Intervention of proven benefit: vaccination
CAP
43.2% vs 39.2%, p=0.005
All-cause CAP hosp
Empyema
All-cause
CAP
hosp Pneumoccous
Radiologic CAP
hospitalization
Pneumococcal CAP
hospitalization
All-cause CAP
hospitalization
CAP hospitalization
Empyema
Annual incidence of
alveolar pneumonia
PCV 7-13
Time-trend analysis
PCV 7-13
Time-trend analysis
England
<2y
Israel
<5y
PCV 7-13
Cohort
PCV 10
Time-series analysis
PCV 10
Cross-sectional
Italy
<5y
Brazil
<2y
Brazil
<2y
Pneumococcal CAP
hospitalization
All-cause CAP
hospitalization
CAP prevalence
South
America
Children
Consolidation CAP
PCV 10
RCT,double-blind
Hib vaccine
Time-series analysis
Vietnam
<5y
Radiologic CAP
Risk for CAP:
Firewood,charcoal use
Cross-sectional
Kenya
Children
New Zealand
<5y
Risk for CAP: smoker
Case control
Philippines
<2y
AUTHOR
YEAR
Moore M
2015
Simonsen L
2014
17-21% reduction in <5y
37-50% reduction in <18y
78.1% reduction
92.4% reduction
Pirez M
2013
Gentile A
2015
20.1 [13.1-26.4], p<0.001
57% reduction
Bruce M
2015
27% reduction
Griffin M
2014
No difference
Saxena S
2015
68% decline in OPD visits
32% decine in hospitalization
Greenberg D
2015
0.58 [0.34-0.99]
Martinelli D
2013
0.43
[0.21-0-90]
23-28% reduction
Afonso E
2013
40% reduction
Abrao MA
2015
Vaccine efficacy:
23.4% [8.8-35.7]
21.5%(20.7-22.2) vs
22.6% (21.9-23.4)
39% reduction
Adverse events
Tregnaghi M
2014
Flasche S
2014
Interventions of potential benefit
Nonsevere CAP
4.2 [3.9-4.6]
Severe CAP
1.1 [1.02-1.26]
CAP
1.99 [1.05-3.81]
Severe CAP
Protective against CAP:
1.breastfeeding >3m
2.no smokers
Case control
Brazil
6m-13y
Association with
hospitalization
for CAP
Protective against
CAP: breastfeeding
Cohort
Kenya
Infants
First physician
diagnosed pneumonia
Ekaru H
2012
Grant V
2012
Tomas A
2012-2015
2.60 [1.57-4.30]
0.53 [0.39-0.73)
[-] association
Barsam F
2013
HIV exposed but
uninfected
Ásbjornsdottir K
2014
3. Interventions requiring more studies to assess benefit in reducing the clinical impact of pneumonia
Vit D
Meta-analysis
[13 studies]
Zinc
Meta-analysis
[3 studies]
Children
Acute lower respiratory
infection [ALRI] severity
Preschool
children
Pneumonia-related
mortality
[+] association between
Vit D deficiency and
increasing severity of ALRI
0.52 [0.11-2.39]
Larkin A
2014
Fu W
2013
37
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38
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Prevalence of Tuberculosis and Bacteraemia in Bangladeshi Children with Severe Malnutrition and Pneumonia Including an Evaluation
of Xpert MTB/RIF Assay. PLoS ONE 2014;9: e93776. doi:10.1371/journal.pone.0093776.
20 Lai E, Nathan A, de Bruyne J, Chan L.: Should all children admitted with community acquired pneumonia have blood cultures taken?
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21 Parikh K, Davis A, Pavuluri P.: Do we need this blood culture? Hosp Pediatr 2014;4:78-84 doi:10.1542/hpeds.2013-0053.
22 Myers A, Hall M, Williams D, Auger K, Tieder J, Statile A, Jerardi K, McClain L, Shah S.: Prevalence of bacteremia in hospitalized
pediatric patients with community-acquired pneumonia. Pediatr Infect Dis J 2013;32:736-40. doi: 10.1097/INF.0b013e318290bf63.
23 McCulloh R, Koster M, Yin D, Milner T, Ralston S, Hill V, Alverson B, Biondi E.: Evaluating the use of blood cultures in the management
of children hospitalized for community-acquired pneumonia. PLoS One 2015;10:e0117462. doi: 10.1371/journal.pone.0117462.
24 Selva L, Benmessaoud R,Lanaspa M, Jroundi I, Moraleda C, Acacio S, Iñigo M, Bastiani A, Monsonis M, Pallares R, Bassat Q, Muñoz-Almagro C:
Detection of Streptococcus pneumoniae and Haemophilus influenzae type B by real-time PCR from dried blood spot samples among children
with pneumonia: a useful approach for developing countries. PLoS One 2013;8:e76970. doi: 10.1371/journal.pone.0076970.
25 Ybanez S, Garcia R.: Prevalence and factors associated with bacteremia in pediatric community-acquired pneumonia in a private tertiary
hospital in Makati from May 2009 to April 2014. Philippine Pediatric Society,Inc. Abstracts Philippine Pediatric Researches 2012-2015.
26 Esposito S, Marchese A, Tozzi A, Rossi G, Da Dalt L, Bona G, Pelucchi C, Schito G, Principi N; Italian Pneumococcal CAP Group:
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27 Chisti M, Ahmed T, Ashraf H, Faruque A, Bardhan P, Dey S, Huq S, Das S, Salam M.:Clinical predictors and outcome of metabolic
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hospitalized with community-acquired pneumonia. Pediatr Emerg Care 2012;28:764-6.
30 Wrotek A, Jackowska T. Hyponatremia in children hospitalized due to pneumonia. Adv Exp Med Biol 2013;788:103-8.
31 Chisti M, Ahmed T, Ashraf H, Faruque AS, Bardhan P, Dey S, Huq S, Das S, Salam M.: Clinical predictors and outcome of metabolic
acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia. PLoS One 2012;7:e39164. doi:
10.1371/journal.pone.0039164.
32 McClain L, Hall M, Shah S, Tieder J, Myers AL, Auger K, Statile A, Jerardi K, Queen M, Fieldston E, Williams D.: Admission chest
radiographs predict illness severity for children hospitalized with pneumonia. J Hosp Med. 2014 ;9:559-64.
33 Basnet S, 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.
34 Jain DL, 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
35 Wrotek A, Jackowska T.: Hyponatremia in children hospitalized due to pneumonia. Adv Exp Med Biol 2013;788:103-8.
36 Williams D, Hall M, Auger K,Tieder J, Jerardi K, Queen M, Statile A, Myers A, Shah S.: Association of White Blood Cell Count and CReactive Protein with Outcomes in Children Hospitalized with Community- Acquired Pneumonia. Pediatr Infect Dis J 2015;34:792–793.
Clinical Question 5. When is antibiotic recommended?
1 Wei L, Liu W, Zhang X, Liu E, Wo Y, Cowling B, Cao W.: Detection of viral and bacterial pathogens in hospitalized children with acute
respiratory illnesses, Chongqing, 2009-2013. Medicine (Baltimore). 2015;94:e742. doi: 10.1097/MD.0000000000000742.
2 Kurz H, Göpfrich H, Huber K, Krugluger W, Asbott F, Wabnegger L, Apfalter P, Sebesta C.: Spectrum of pathogens of in-patient children
and youths with community acquired pneumonia: a 3 year survey of a community hospital in Vienna, Austria. Wien Klin Wochenschr.
2013;125(21-22):674-9. doi:10.1007/s00508-013-0426-z.
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 Jain S, Williams D, Arnold S, Ampofo K, Bramley A, Reed C, Stockmann C, Anderson E, Grijalva C, Self W, Zhu Y, Patel A, Hymas W,
Chappell J, Kaufman R, Kan J, Dansie D, Lenny N, Hillyard D, Haynes L, Levine M, Lindstrom S, Winchell J, Katz J, Erdman D,
Schneider E, Hicks LA, Wunderink R, Edwards K, Pavia A, McCullers J, Finelli L; CDC EPIC Study Team.: Community-acquired
pneumonia requiring hospitalization among U.S. children N Engl J Med. 2015; 372:835-45. doi: 10.1056/NEJMoa1405870.
6 Lagare A, Maïnassara HB, Issaka B, Sidiki A, Tempia S.: Viral and bacterial etiology of severe acute respiratory illness among children < 5
years of age without influenza in Niger. BMC Infect Dis 2015;15:515. doi: 10.1186/s12879-015-1251-y.
39
7 Elemraid M, Sails A, Eltringham G, Perry J, Rushton S, Spencer D, Thomas M, Eastham K, Hampton F, Gennery A, Clark J; North East of
England Paediatric Respiratory Infection Study Group.: Aetiology of paediatric pneumonia after the introduction of pneumococcal
conjugate vaccine. Eur Respir J 2013;42:1595-603. doi:10.1183/09031936.00199112.
8 Chen C, Lin P, Tsai M, Huang C, Tsao K, Wong K, Chang L, Chiu C, Lin T, Huang Y.: Etiology of community-acquired pneumonia in
hospitalized children in northern Taiwan. Pediatr Infect Dis J. 2012;31:e196-201. doi:10.1097/INF.0b013e31826eb5a7.
9 Mathew J, Singhi S, Ray P, Hagel E, Saghafian-Hedengren S, Bansal A, Ygberg S, Sodhi K, Kumar B, Nilsson A.: Etiology of community
acquired pneumonia among children in India: prospective, cohort study. J Glob Health 2015;5:050418.doi:10.7189/jogh.05.020418.
10 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.
11 Banstola A.: The epidemiology of hospitalization for pneumonia in children under five in the rural western region of Nepal: a descriptive
study. PLoS One 2013; 8:e71311.doi:10.1371/journal.pone.0071311.
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 communityacquired 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 ofcommunityacquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis. Int J Infect Dis 2012;16:e515. 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 communityacquired 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, temperature 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.
Clinical Question 11. What ancillary treatment can be given?
1 Rojas-Reyes M, Granados Rugeles C, Charry-Anzola L.: Oxygen therapy for lower respiratory tract infections in children between 3 months and
15 years of age. Cochrane Database of Systematic Reviews 2014,Issue 12.Art.No.: CD005975.DOI:10.1002/14651858.CD005975.pub3.
2 Chisti M, Salam M, Smith J, Ahmed T, Pietroni M, Shahunja K, Shahid A, Faruque A, Ashraf H, Bardhan P, Sharifuzzaman, Graham S,
Duke T.: Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open,
randomised controlled trial Lancet. 2015;386:1057-65. doi:10.1016/S0140-6736(15)60249-5.
3 Srinivasan M, Ndeezi G, Mboijana C, Kiguli S, Bimenya G, Nankabirwa V, Tumwine J.: Zinc adjunct therapy reduces case fatality in severe
childhood pneumonia: a randomized double blind placebo-controlled trial. BMC Med 2012;10:14.doi:10.1186/1741-7015-10-14.
4 Rulloda M.: Zinc as adjunct therapy for treating pneumonia in children 6 months old to 5 years of age: a 3 month prospective, randomized,
double blind, placebo-controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
5 Justina M.: Use of systemic corticosteroid as adjunct therapy among hospitalized children with community-acquired pneumonia. Philippine
Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.
6 Guinto M.: Efficacy of zinc as an adjunct to amoxicillin in the treatment of nonsevere pneumonia in children 6 months to 5 years old at
Angeles University Foundation Medical Center Philippine. Pediatric Society,Inc. Abstracts Philippine Pediatric Researches 2012-2015.
7 Chang C, Cheng A, Chang A.: Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children
and adults. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD006088. DOI:10.1002/14651858.CD006088.pub4.
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;97:138794.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.
Clinical Question 12. How can pneumonia be prevented?
1 Field Health and Information Services Annual Report 2012. Department of Health National Epidemiology Center Public Health Surveillance
and Informatics Division Manila, Philippines.
2 Field Health and Information Services Annual Report 2013. Department of Health National Epidemiology Center Public Health Surveillance
and Informatics Division Manila, Philippines.
3 Field Health and Information Services Annual Report 2014. Department of Health National Epidemiology Center Public Health Surveillance
and Informatics Division Manila, Philippines.
4 ICD 10 Registry, Committee on Registry of Childhood Disease, Philippine Pediatric Society, Inc.
5 Liu L, Oza S, Hogan D, Perin J, Rudan I , Lawn J, Cousens S , Mathers C, Black R.: Global, regional, and national causes of child mortality
in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015;385:430-40. doi:
10.1016/S0140-6736(14)61698-6.
6 Tumanan-Mendoza B, Mendoza V, Punzalan F, Reganit P, Bacolcol S.: Economic Burden of Community-Acquired Pneumonia among
Adults in the Philippines: Its Equity and Policy Implications in the Case Rate Payments of the Philippine Health Insurance Corporation.
Value in Health Regional Issues 6C; 2015;118–125
7 Moore M, Link-Gelles R, Schaffner W, Lynfield R, Lexau C, Bennett N, Petit S, Zansky S, Harrison L, Reingold A, Miller L, Scherzinger K,
Thomas A, Farley M, Zell E, Taylor T, Pondo T, Rodgers L, McGee L, Beall B, Jorgensen J, Whitney CG.: Effect of use of 13-valent
pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite,
population-based surveillance. Lancet Infect Dis 2015;15:301-9.doi:10.1016/S1473-3099(14)71081-3.
8 Simonsen L, Taylor R, Schuck-Paim C, Lustig R, Haber M, Klugman K.:Effect of 13-valent pneumococcal conjugate vaccine on admissions
to hospital 2 years after its introduction in the USA: a time series analysis Lancet Respir Med. 2014;2:387-94. doi: 10.1016/S22132600(14)70032-3.
9 Pírez M, Algorta G, Chamorro F, Romero C, Varela A, Cedres A, Giachetto G.: Changes in hospitalizations for pneumonia after universal
vaccination with pneumococcal conjugate vaccines 7/13 valent and haemophilus influenzae type b conjugate vaccine in a Pediatric
Referral Hospital in Uruguay. Pediatr Infect Dis J 2014;33:753-9. doi:10.1097/INF.0000000000000294.
10 Gentile Á, Juarez Mdel V, Luciön M, Romanin V, Giglio N, Bakin J. Influence of respiratory viruses on the evaluation of the 13-valent
pneumococcal conjugate vaccine effectiveness in children under 5 years old: A time-series study for the 2001-2013 period. Arch Argent
Pediatr 2015;113:310-6. doi:10.1590/S0325-00752015000400006
11 Bruce M, Singleton R, Bulkow L, Rudolph K, Zulz T, Gounder P, Hurlburt D, Bruden D, Hennessy T.: Impact of the 13-valent
pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska Vaccine. 2015;33:4813-9. doi:
10.1016/j.vaccine.2015.07.080.
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 10valent 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
protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial. PLoS Med. 2014;
11:e1001657.doi:10.1371/journal.pmed.1001657. Erratum in: PLoS Med. 2015;12:e1001850.
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
vaccination against Haemophilus influenzae type b in Nha Trang, Vietnam.Vaccine 2014;32:6963-70. doi:10.1016/j.vaccine.2014.10.055.
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
factors for community-acquired pneumonia in pre-school-aged children. J Paediatr Child Health 2012;48:402-12. doi:10.1111/j.14401754.2011.02244.x.
22 Tomas A, Resurreccion M.: A hospital based case control study on the association of selected maternal risk taking behaviors in the
development of community-acquired pneumonia among infants. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric
Researches 2012-2015.
23 Barsam F, Borges G, Severino A, de Mello L, da Silva A, Nunes A.: Factors associated with community-acquired pneumonia in
hospitalised children and adolescents aged 6 months to 13 years old. Eur J Pediatr 2013;172:493-9. doi:10.1007/s00431-012-1909z.
24 Ásbjörnsdóttir KH, Slyker JA, Weiss NS, Mbori-Ngacha D, Maleche-Obimbo E Wamalwa D, John-Stewart G.: Breastfeeding is associated
with decreased pneumonia incidence among HIV-exposed, uninfected Kenyan infants. AIDS. 2013;27:2809-15. doi:
10.1097/01.aids.0000432540.59786.6d.
25 Fu W, Ding L-R, Zhuang C, Zhou Y-H (2013) Effects of Zinc Supplementation on the Incidence of Mortality in Preschool Children: A MetaAnalysis of Randomized Controlled Trials. PLoS ONE 2013;8:e79998. doi:10.1371/journal.pone.0079998
26 Larkin A, Lassetter J.: Vitamin D deficiency and acute lower respiratory infections in children younger than 5 years: identification and
treatment. J Pediatr Health Care 2014;28:572-82; quiz 583-4. doi:10.1016/j.pedhc.2014.08.013
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?
2004 SUMMARY RECOMMENDATION.
Predictors of community-acquired pneumonia in a patient with cough
1. for ages 3 months to 5 years are tachypnea and/or chest indrawing [Recommendation Grade B].
2. for ages 5 to 12 years are fever, tachypnea, and crackles [Recommendation Grade D].
3. beyond 12 years of age are the presence of the following features [Recommendation Grade D]: 3.1. fever, tachypnea, and
tachycardia; and 3.2. at least one abnormal chest findings of diminished breath sounds, rhonchi, crackles or wheezes.
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
The likelihood of radiologic pneumonia at the Emergency Room in a patient with cough is highest at ages 3 months to 5 years if any of the
following is present: [a] RR>50/min,nasal flaring,and oxygen saturation<96%; or [b] tachypnea and chest indrawing; or [c]chest indrawing.
CQ 2. WHO WILL REQUIRE ADMISSION?
2004 SUMMARY RECOMMENDATION.
1. A patient at moderate to high risk to develop pneumonia-related mortality should be admitted [Recommendation Grade D].
2. A patient at minimal to low risk can be managed on an outpatient basis [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. Additional variables for considering admission include lack of measles and Hib vaccination, high oxygen requirement on admission, and
chest indrawing.
2. Admissible patients may be managed in a day care setting.
CQ 3. WHAT DIAGNOSTIC AIDS ARE INITIALLY REQUESTED FOR A PATIENT CLASSIFIED AS
EITHER pCAP A or pCAP B BEING MANAGED IN AN AMBULATORY SETTING?
2004 SUMMARY RECOMMENDATION.
No diagnostic aids are initially requested for a patient classified as either pCAP A or pCAP B who is being managed in an ambulatory
setting [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
The low risk for bacteremia [1.6% (95% CI 0.7-2.9) among patients aged 2-24 months with nonsevere pneumonia does not warrant blood
culture determination.
CQ 4. WHAT DIAGNOSTIC AIDS ARE INITIALLY REQUESTED FOR A PATIENT CLASSIFIED AS
EITHER pCAP C or pCAP D BEING MANAGED IN A HOSPITAL SETTING?
2004 SUMMARY RECOMMENDATION.
1.The following should be routinely requested:
1.1. Chest x-ray PA-lateral [Recommendation Grade B].
1.2. White blood cell count [Recommendation Grade C].
1.3. Culture and sensitivity of 1.3.1. Blood for pCAP D [Recommendation Grade D].
1.3.2. Pleural fluid [Recommendation Grade D].
1.3.3. Tracheal aspirate upon initial intubation
[Recommendation Grade D].
1.4. Blood gas and/or pulse oximetry [Recommendation Grade D].
2.The following may be requested: culture and sensitivity of sputum for older children [Recommendation Grade D].
3. The following should not be routinely requested: 3.1. Erythrocyte sedimentation rate [Recommendation Grade A].
3.2. C-reactive protein [Recommendation Grade A].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. Chest radiographic evaluation is primarily utilized as an integral part of a clinical prediction rule in identifying the presence of a bacterial
pathogen. As an individual tool, it can be used to assess severity and presence of complications, and to predict subsequent course of
illness.
2. WBC or CRP has a limited value as an individual test in differentiating bacterial from viral pneumonia. A CRP level [≥ 12 mg/dl] is
associated with necrotizing pneumonia and/or empyema.
3. Single evidence suggests a 63 mm/h value for ESR in predicting the presence of a bacterial pathogen.
4. The microbiologic yield for blood culture ranged from 1.2% to 6.2%.
5. High oxygen requirement on admission is one of the variables associated with mortality.
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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].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT
1. Epidemiology. 1.1. Recent epidemiologic trend shows that more than 50% of hospitalized cases of pCAP will require antibiotic.
1.2. The importance of mixed infection as causative agents should be clarified as it is responsible for about one-third of
all identified causes of hospitalized pCAP.
2. Microbiologic tests. The yield in detecting bacteremia in pCAP remains to be low at 1.2% to 26%.
3. Predictors of bacterial pathogen. 3.1. A clinical prediction rule that makes use of a bacterial pneumonia score [BPS] of > 4 can predict
the presence of a bacterial pathogen in hospitalized patients aged one month to five years.
3.2. Other individual parameters include the following:
3.2.1. Increasing age generally correlates with the presence of antibiotic-requiring pathogen.
Identifying a specific as to when an antibiotic should be started is difficult.
3.2.2. There is a single evidence in the use of ESR with a value of 63 mm/hr in predicting the
presence of bacterial pathogen.
3.2.3. There is a weak evidence in the use of clinical symptomatology, chest x-ray, WBC and CRP
as predictors of bacterial pathogen.
CQ 6. WHAT EMPIRIC TREATMENT SHOULD BE ADMINISTERED IF A BACTERIAL ETIOLOGY IS STRONGLY CONSIDERED?
2004 SUMMARY RECOMMENDATION.
1. For a patient classified as pCAP A or pCAP B without previous antibiotic, amoxicillin [40-50 mg/kg/day in 3 divided doses] is the drug of
choice [Recommendation Grade D].
2. For a patient classified as pCAP C without previous antibiotic and who has completed the primary immunization against Haemophilus
influenzae type b, penicillin G [100,000 units/kg/day in 4 divided doses] is the drug of choice [Recommendation Grade D]. If a primary
immunization against Hib has not been completed, ampicillin [100 mg/kg/day in 4 divided doses] should be given [Recommendation Grade D].
3. For a patient classified as pCAP D, a specialist should be consulted [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. Epidemiology. 1.1. Epidemiologic trend in developed economies suggests that Streptococcus pneumoniae and Mycoplasma
pneumoniae appear to be the most common pathogens causing community-acquired pneumonia across all ages.
1.2 An important emerging pathogen is community-acquired methicillin-resistant Staphylococcus aureus [CA-MRSA].
2. Antibiotic resistance. Data on 2006 Antimicrobial Resistance Surveillance Program showed resistance rate of less than 10% for
penicillin and chloramphenicol with Streptococcus pneumoniae, and for ampicillin with Haemophilus influenzae.
3. Empiric antibiotic therapy. 3.1. For pCAP A and pCAP B [nonsevere pneumonia], there is evidence for the use of amoxicillin [45 mg/kg/day in
three divided doses] for a minimum duration of 3 days. For those with known hypersensitivity to amoxicillin, a macrolide may be considered. The use of cotrimoxazole is discouraged because of high failure and resistance rates.
3.2. For pCAP C [severe pneumonia], equal efficacies were noted between oral amoxicillin and parenteral
penicillin among patients who can tolerate feeding, and between monotherapy and combination therapy for
those who cannot tolerate feeding. Among monotherapy available for use, ampicillin is the best choice
considering its cost.
3.3. For a patient classified as pCAP D, a specialist should be consulted.
CQ 7. WHAT TREATMENT SHOULD BE INITIALLY GIVEN IF A VIRAL ETIOLOGY IS STRONGLY CONSIDERED?
2004 SUMMARY RECOMMENDATION.
1. Ancillary treatment should only be given [Recommendation Grade D].
2. Oseltamivir [2 mg/kg/dose BID for 5 days] or amantadine [4.4-8.8 mg/kg/day for 3-5 days] may be given for influenza that is either
confirmed by laboratory [Recommendation Grade B] or occurring as an outbreak [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
Oseltamivir remains to be the drug of choice for laboratory confirmed cases of influenza.
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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.
CQ 9. WHAT SHOULD BE DONE IF A PATIENT IS NOT RESPONDING TO CURRENT ANTIBIOTIC THERAPY?
2004 SUMMARY RECOMMENDATION.
1. If an outpatient 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]: a. change the initial antibiotic; or b. start an oral macrolide; or c. reevaluate diagnosis.
2. If an inpatient classified as pCAP C is not responding to the current antibiotic within 72 hours, consider consultation with a specialist
because of the following possibilities [Recommendation Grade D]: a. penicillin-resistant Streptococcus pneumoniae; or b. presence
of complications [pulmonary or extrapulmonary]; or c. other diagnosis.
3. If an inpatient classified as pCAP D is not responding to the current antibiotic within 72 hours, consider immediate consultation with a
specialist [Recommendation Grade D].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. There are no studies dealing with therapeutic interventions following treatment failure among children having CAP.
2. A definition of treatment failure for nonsevere pneumonia is as follows:
a. Same status. This is defined as RR > age-specific range but +5 breaths/min to the baseline reading and without lower chest
indrawing or any danger signs; b. Worse status. This is defined as developing lower chest indrawing or with any of the danger signs.
3. The causes of treatment failure include coinfection with respiratory syncytial virus or mixed infection, non-adherence to treatment for
nonsevere pneumonia, resistance to antibiotics, clinical sepsis, and progressive pneumonia.
CQ 10. WHEN CAN SWITCH THERAPY IN BACTERIAL PNEUMONIA BE STARTED?
2004 SUMMARY RECOMMENDATION.
Switch from intravenous antibiotic administration to oral form 2-3 days after initiation of antibiotic is recommended in a patient
[Recommendation Grade D] who 1. is responding to the initial antibiotic therapy; 2. is able to feed with intact gastrointestinal absorption;
and 3. does not have any pulmonary or extrapulmonary complications.
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
Switch therapy from three [3] days of IV ampicillin to four [4] days of either amoxicillin or cotrimoxazole may be used among patients
admitted because of community acquired pneumonia. Amoxicillin is preferred because of high failure and resistance rates reported in the
use of cotrimoxazole.
CQ 11. WHAT ANCILLARY TREATMENT CAN BE GIVEN?
2004 SUMMARY RECOMMENDATION.
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].
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. There is no evidence to support the use of hydration or fluid restriction and cough preparation in the management of pneumonia.
2. The value of elemental zinc or vitamin A is inconclusive.
3. Single study demonstrated benefit for either virgin coconut oil or probiotic as adjunct therapy in pneumonia.
CQ 12. HOW CAN PNEUMONIA BE PREVENTED?
2004 SUMMARY RECOMMENDATION.
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.
2008 FIRST PAPP UPDATE SUMMARY HIGHLIGHT.
1. A meta-analysis on immunomodulators showed a general reduction of rates in acute respiratory tract infection through the use of
immunostimulants.
2. There are evidences to suggest that handwashing using antibacterial soaps, pneumococcal and Hib vaccination, elemental zinc, and
breastfeeding are effective in preventing pneumonia.
3. Single study showed that patients on gastric acid inhibitors are at an increase risk to have pneumonia.
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