DRAFT JULY 2017 TASK 2016 pcap CPG...2 PHILIPPINE ACADEMY OF PEDIATRIC PULMONOLOGISTS, Inc. [PAPP,...

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

2

PHILIPPINE ACADEMY OF PEDIATRIC PULMONOLOGISTS, Inc. [PAPP, Inc.]

2016 PAPP Task Force on pCAP: 3rd 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: [email protected]. 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 Chair Emily B. Gaerlan-Resurreccion, MD FPPS FPAPP Secretary Vivian A. Ancheta, MD FPPS FPAPP Member Gari D. Astrologio, MD DPPS DPAPP Member Janet C. Bernardo, MD FPPS FPAPP Member Alfredo L. Bongo Jr, MD FPPS FPAPP Member Janet Myla Q. Bonleon, MD FPPS FPAPP Member Lydia K. Chang, MD FPPS FPAPP Member Edward A. Chua, MD DPPS DPAPP Member Julie Iris C. Clapano, MD FPPS DPAPP Member Amelia G. Cunanan, MD FPPS FPAPP Member Beverly D. de la Cruz, MD FPPS DPAPP Member Anjanette R. de Leon, MD FPPS FPAPP Member Yadnee V. Estrera, MD DPPS DPAPP Member Jean Marie E. Jamero, MD DPPS DPAPP Member Arnold Nicholas T. Lim, MD DPPS DPAPP Member Grace V. Malayan, MD FPPS FPAPP Member Beatriz Praxedez Apolla I. Mandanas, MD DPPS DPAPP Member Raymund Anthony L. Manuel, MD DPPS DPAPP Member Vicente Carlomagno D. Mendoza, MD FPPS DPAPP Member Doris Louise C. Obra, MD FPPS FPAPP Member Catherine S. Palaypayon, MD DPPS DPAPP Member Cynthia Theresa M. Rimando, MD FPPS DPAPP Member Ernesto Z. Salvador, MD DPPS DPAPP Member Marion O. Sanchez, MD FPPS FPAPP Member Josy Naty M. Venturina, MD DPPS DPAPP Member Rozaida R. Villon, MD FPPS FPAPP Member Nilyn Elise O. Ygnacio, MD DPPS DPAPP Member Dahlia L. Yu, MD DPPS DPAPP Member

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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

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PREFACE

The Philippine Pediatric Society in 2004 spearheaded the publication of the Clinical Practice Guideline in the Evaluation and Management of Pediatric Community-acquired Pneum onia [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.

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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 situat ions]. 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. In preparation for the 4th 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 2nd and 3rd Updates are summarized below. SECTION KEY DIFFERENCES

2012 2016 A. Methodology

1. Microbial etiology Virus, bacteria and Mtb Virus and bacteria 2. Geographic distribution of

Task force membership MetroManila MetroManila, MetroCebu and MetroDavao

3. Literature review Jan 2008 to Dec 2011 Jan 2012 to Dec 2016 4. Definition of level of

evidence and grading of recommendation

Based on Sacket DL, Straus SE: Evidence Based Medicine 2000

Developed by the 2016 PAPP Task Force in pCAP

5. Geographic distribution of stakeholders

MetroManila Nationwide

B. Summary recommendations 1. Appraisal

Clinical Question1

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 Clinical Question 2 No significant change Clinical Question 3 No significant change Clinical Question 4 1. Addition of lung ultrasound and anaerobic culture

as diagnostic tests 2. Removal of diagnostic test for tuberculosis

Clinical Question 5 1. Additional test to determine necessity of antibiotic administration

2. No recommendation for pCAP A or B 2. Therapeutic approach

Clinical Question 6 No significant change Clinical Question 7 Addition of zanamivir Clinical Question 8 Addition of deifinition of clinical stability Clinical Question 9 No significant change Clinical Question 10 No significant change Clinical Question 11 Zinc may be beneficial

3. Preventive strategies Clinical Question 12 Zinc may not be beneficial

Cristan Q. Cabanilla, MD FPAPP FPPS Chair 2016 PAPP Task Force on pCAP

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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 to 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. Gaerlan- Resurreccion, 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 PAPP 1st Update, and 2012 PAPP 2nd Update in the Evaluation and Management of Pediatric Community- acquired 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 nd 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.

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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 RECOMMENDATION STATEMENT DESCRIPTION OF EVIDENCE

A A1 Should [or should not] be recommended1. Definite evidence for benefit [or without benefit] based on at least 1 meta-

analysis of descriptive or randomized controlled trials, or at least 2 separate descriptive or randomized controlled trials, with similar intervention, study design, outcome AND result.

A2 Strong evidence exists to [or not to] be recommended but with reservation2.

B

B1 May [or may not ] be recommended. Equivocal evidence for benefit [or without benefit] based on multiple meta- analysis of descriptive or randomized controlled trials, or at least 2 separate descriptive or randomized trials with dissimilar intervention, outcome, study design OR results.

B2 May [or may not] be recommended but with reservation2.

C

C1 May [or may not] be recommended. Evidence for benefit [or without benefit] based on only one descriptive or randomized controlled trial. C2 May [or may not] be recommended but with

reservation2.

D May [or may not] be recommended. Evidence for benefit [or without benefit] based on consensus opinion of at least three-fourths of committee members of each clinical question

1Recommendation as a routine [or not a routine] intervention. 2Conditional 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. 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 periodic evaluation will be used for formulating the 4th PAPP Update in the Evaluation and Management of Pediatric Community-acquired Pneumonia [2020].

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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.

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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

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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 neu-

rologic, 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.

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PREDICTOR

PATIENTS [n]

AGE

ODDS RATIO [95%CI]

SPECIFICITY

POSITIVE PREDICTIVE

VALUE

p VALUE

AUTHOR / YEAR

Emergency room as site-of-care Oxygen saturation

1

<90% 147 <5y 68% Modi P,2013 <92% 126 6m-18y 0.01 Muthukrishnan L,2013 <94% 3,204 1m-5y 5.90 (3.55-9.80) Nijman R,2013

Clinical presentation

Difficulty of breathing 165 1-16y 63% Alagadan S,2015 Tachypnea

[WHO-defined, age-specific]

147

<5y

72%

Modi P,2013

Tachypnea [PALS cut-off, age specific] 3,204 1m-5y

1.55 (0.99-2.42) Nijman R,2013

Chest wall retractions 147 <5y 8-11% Modi P,2013 3,204 1m-5y 2.11 (1.35-3.32) Nijman R,2013

Fever 147 <5y 6% Modi P,2013 126 6m-18y 0.006 Muthukrishnan L,2013

Grunting

147

<5y

100%

Modi P,2013

Wheezing 40% Decreased breath sounds 38%

Nasal flaring 18%

Cyanosis 5% Localized chest findings 126 6m-18y 0.001 Muthukrishnan L,2013

Predictive score2

> 9 300 3m–5y 95.7% (87.2%–98.9%)

Arquiza T,2013

Emergency room or ward as site-of-care Lung ultrasound

3

Consolidation 765 <18y 84% (80%–88%) Pereda M,2015 Outpatient clinic as site-of-care

Risk predictive score2

> 35.8 120 3m-5y 100% Domingo E, 2013

SUMMARY OF EVIDENCE 1. Reference standard The 2016 PAPP Task Force on pCAP has retained the position statement of the 2012 PAPP 2nd 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.

INITIAL PRESENTATION PATIENTS [n] AGE RADIOGRAPHIC PNEUMONIA

AUTHOR/YEAR Positive Negative

Emergency room as the site of care

Cough or difficulty of breathing 147

<5y

58% 42% Modi P,2013

Cough or difficulty of breathing and

WHO-defined, age-specific tachypnea

324

34%

---

Wingerter S,2012

3. Predictors of pneumonia with chest x-ray as the reference standard 3.1. Positive predictors

1Determination of oxygen saturation at room air is desirable in situation where pulse oximeter is available. 2Unlike 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.

3Subgroup 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.

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PREDICTOR PATIENTS [n]

AGE

SENSITIVITY

AUTHOR/YEAR

Emergency room as site-of-care Oxygen saturation

1

147

<5y

<94% 86%

Modi P,2013

Clinical presentation Fever 93%

Nasal flaring 91% Chest wall retractions 81-85%

Decreased breath sounds 70% Wheezing 44% Grunting 40%

Tachypnea [WHO defined. age-specific]

37%

Emergency room or ward as site-of-care Lung ultrasound

2

Consolidation 765 <18y 96% (94%–98%) Pereda M,2013

3.2. Negative predictors

1Determination of oxygen saturation at room air is desirable in situation where pulse oximeter is available. 2Subgroup 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

PATIENTS

[n]

AGE

CLINICAL PREDICTOR OF

RADIOGRAPHIC PNEUMONIA

ODDS RATIO FOR CLINICAL PREDICTOR

OF RADIOGRAPHIC PNEUMONIA

[CI 95%]

AUTHOR/YEAR

Emergency room as site-of-care Diarrhea with hypokalemia Prospective cohort 180 0-59m Tachypnea 0.36 [0.17-0.34] p=0.005 Chisti M,2013

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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

VARIABLESb

Clinical

1. Dehydrationc None Mild Moderate Severe

2. Malnutritiond None Moderate Severe

3. Pallor None Present Present 4. Respiratory rate a. 3 to12 monthse

b. 1 to 5 yearse

c. >5 years

>50/min to <60/min >40/min to <50/min >30/min to <35/min

>60/min to <70/min >50/min >35/min

>70/min >50/min >35/min

5. Signs of respiratory failure a. Retraction b. Head bobbing c. Cyanosis d. Grunting e. Apnea f. Sensorial changes

None None None None None None

Intercostal / subcostal Present Present

None None

Irritable

Supraclavicular / IC / subcostal Present Present Present Present

Lethargic / stuporous / comatose Diagnostic aid at site-of-care

f

1. Chest x-ray findings of any of the following: effusion; abscess; air leak or lobar consolidation

None Present Present

2. Oxygen saturation at room air using pulse oximetry 95% <95% <95% ACTION PLAN

1. Site-of-care Outpatient Admit to ward Admit to a critical care facility 2. Follow-up End of treatment

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]

aIn order to classify to a higher risk category, at least 2 variables (clinical and diagnostic aid) should be present. In the absence of a diagnostic aid variable, clinical variables will suffice. b Risk factors for mortality based on evidence and/or expert opinion among members of the 2012 PAPP Task Force on pCAP.

c Weight for Height SD score< -2 moderate; SD score< -3 severe. WHO management of severe malnutrition: a manual for physicians and other health workers. Geneva. WHO 1999.

d Grading of dehydration adapted from Nelson’s Textbook of Pediatrics: MILD [thirsty, normal or increased pulse rate, decreased urine output and normal physical examination];

MODERATE [tachycardia, little or no urine output, irritable/lethargic, sunken eyes and fontanel, decreased tears, dry mucus membranes, mild tenting of the skin, delayed capillary refill, cool and pale]; SEVERE [rapid and weak pulse, decreased BP, no urine output, very sunken eyes and fontanel, no tears, parched mucous membranes, tenting of the skin, very delayed capillary refill, cold and mottled].

e World Health Organization age-specific criteria for tachypnea for children under 5 years old.

f Chest x-ray and pulse oximetry are desirable variables but not absolutely necessary as determinants of admission at site-of-care.

2. Patients under 5 years old [Recommendation Grade B] and more than 5 years old [Recommendation Grade D] who are classified as

pCAP C but whose chest x-ray is without any of the following: effusion, lung abscess, air leak or multilobar consolidation, and whose oxygen saturation is >95% at room air can be managed initially on an outpatient basis.

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].

PARAMETERS IDENTIFIED AT

INITIAL SITE-OF-CARE

RISK CLASSIFICATION1

pCAP A pCAP B pCAP C Severe or moderate risk

pCAP D Very severe or high risk Nonsevere

Clinical parameters2

1. Respiratory signs 1.1. Retraction 1.2. Head bobbing 1.3. Cyanosis 1.4. Grunting 1.5. Apnea 1.6. Tachypnea

1.6.1. 3 to12 months3

1.6.2. 1 to 5 years3

1.6.3. >5 years

None None None None None

>50/min to <60/min >40/min to <50/min >30/min to <35/min

Intercostal / subcostal

Present Present None None

>60/min to <70/min

>50/min >35/min

Supraclavicular / IC / subcostal

Present Present Present Present

>70/min >50/min >35/min

1In 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.

2Risk factors for mortality based on evidence and/or expert opinion among members of the 2016 PAPP Task Force on pCAP. 3World 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.

14

STUDY DESCRIPTION

RISK FACTORS

n/N [%] ODDS RATIO [95%CI]

P VALUE

AUTHOR/YEAR DESIGN AGE

Cohort

<59m

Severe malnutrition

49/85 [57.6%] 1.85 (1.03-3.32) 0.020 Ramachandran P,20121

1.91 (0.67–4.92) 0.230 Agweyu A,2014 1.37 (0.35–5.31) Webb C, 2012

Altered consciousness 22/85 [25.9%] 14.49 (4.49-51.88) 0.001 Ramachandran P,20121

1.02 (0.40–2.59) 0.970 Agweyu A,2014 Convulsion 11.15 (3.38-40.59) 0.001 Ramachandran P,20121

6.83 (2.01–23.2) Webb C 2012

Age 1 to 6m 49/85 [57.7%] 2.77 (1.57-4.91) 0.001 Ramachandran P,20121

2 to11m 1.80 (0.57–5.67) 0.310 Agweyu A,2014

Shock 9.99 (3.36–29.7) Webb C,2012 4/85 [4.7%] 0.51 (0.14-1.72) 0.230 Ramachandran P,20121

<12y Increasing severity2 3.20 (1.20-8.90) 0.020 Ferreira S,2014

<59m

Inability to drink 6.39 (1.40–29.23) 0.006 Agweyu A,2014 Congenital heart disease 10/85 [11.8%] 5.53 (1.53-21.72) 0.001 Ramachandran P,20121

Head nodding 2.15 (0.84–5.50) 0.100 Agweyu A,2014 Central cyanosis 1.85 (0.56–6.08) 0.300

Grunting 0.71(0.27–1.86) 0.490 SpO2 <90% 0.31 (0.07–1.42) 0.110

STUDY DESCRIPTION INTERVENTION MORTALITY

RATE TREATMENT FAILURE RATE

AT DAY 14 AUTHOR/YEAR DESIGN AGE

RCT

<59m

7 days oral amoxicillin at home vs

7 days oral amoxicillin for 48 hours at hospital followed by 5 days at home

0.2% [1/554] vs

0.2% [1/564]

10.8% (60/554)

vs 18.1% (102/564)

Patel A,2015

2. Central nervous system signs 2.1. Altered sensorium 2.2. Convulsion

None None

Irritable Present

Lethargic / stuporous / comatose

Present 3. Circulatory signs

3.1. Poor perfusion 3.2. Pallor

None None

Capillary refill >3s

Present

Shock

Present 4. General considerations

4.1. Malnutrition4

4.2. Inability to drink 4.3. Comorbid conditions

None

No None

Mild No Present

Moderate

Yes Present

Severe

Yes Present

Ancillary parameters5

5. Chest x-ray findings of effusion, abscess, air leak or multilobar consolidation

None

Present

Present

6. Oxygen saturation at room air using pulse oximetry

95%

91% to 94%

<90% 4Weight 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. 5Chest 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.

1Radiologic pneumonia cases 2Multivariate analysis

3. Composite risk factors for subsequent mortality within 48 hours at initial site-of-care This is a gap in current knowledge. There are no published data available for review.

4. Management of pCAP C on an outpatient basis

15

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.


**Please see Methodology for description of current grading of recommendation.

16

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]


**Please see Methodology for description of grading of recommendation.

17

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

ODDS RATIO [95% CI]

YIELD [%]

p VALUE

SPECIFICITY [95% CI]

AUTHOR/YEAR

C-reactive protein [CRP] : >80 mg/L Bacterial/atypical vs viral pathogen Prospective cohort

3.6 [1.65–8.07]

0.001

Elemraid M,2014

CRP : elevated Pneumococcal vs viral pathogen Prospective cohort

19 [5-75]

Galetto-Lacour A,2013

CRP : elevated Bacterial vs viral pathogen Retrospective cohort

0.020

Hoshina T,2014

CRP : > 200 ug/ml Bacterial pathogen Case control

56.10%

Huang H,2014

CRP : abnormal Mycoplasma p vs non-Mycoplasma p Cross-sectional

30.9% vs

23.7%

0.002

Gao J,2015

Procalcitonin [PCT] : elevated Bacterial vs non-bacterial pathogen Prospective cohort

23 [5-117]

Galetto-Lacour A,2013

PCT : elevated Pneumococcal vs non-bacterial pathogen Retrospective cohort

0.0008

Hoshina T,2014

Lipocalin 2 : >130.1 ng/ml Probable bacterial pathogen Case control

85.7%

Huang H,2014

Chest x-ray : pneumonia Pneumococcal infection Cross-sectional

93% [80-98]

Nascimento-Carvalho C,2015

IgM assay : 1.65 mean value Mycoplasma pneumoniae Cross-sectional

96.93% [reference std:

RT-PCR]

Medjo B,2014

White blood cell count [WBC] : abnormal Mycoplasma p vs non-Mycoplasma p Cross-sectional

65.5% vs

55.2%

0.001

Gao J,2015

WBC : abnormal Bacterial vs non-bacterial pathogen Cohort

Not significant

Hoshina T,2014

WBC : >15 × 109/L Bacterial vs viral pathogen Prospective cohort

0.5 [0.13–1.96]

0.320

Elemraid M,2014

18

9 Neutrophil count : >10 × 10 /L Bacterial vs viral pathogen Prospective cohort

5.9 [1.47–23.94]

0.012

Elemraid M,2014

Neutrophil count : abnormal Bacterial vs non-bacterial pathogen Cohort

Not significant

Hoshina T,2014

Neutrophil to lymphocyte ratio : 2.7 Bacterial vs viral pathogen Retrospective cohort

<0.001

Bekdas M,2014

CRP to mean platelet volume ratio : 11.0 Bacterial vs viral pathogen Retrospective cohort

<0.001

2. Clinically important endpoint: radiologic evidence of clinical suspicion of necrotizing pneumonia, multilobar consolidation, lung abscess, pleural effusion, pneumothorax or pneumomediastinum

CONDITION DIAGNOSTIC AID INCIDENCE AUTHOR / YEAR

Necrotizing pneumonia Chest x-ray 32/882 [3.7%] Krenke K,2015

Lung ultrasound 10/140 [7.1%] Lai S,2015 Lung ultrasound + CT scan 70/96 [72.1%]

3. Clinically important endpoint: determination of underlying microbial etiology The Task Force recognizes the trade-off between the need to identify microbial etiology and the cost-benefit ratio in terms of actual yield. There are no local data available for review.

SPECIMEN : FINDINGS TECHNIQUE / STUDY DESIGN

YIELD n/N [%, CI 95%]

REMARKS

AUTHOR/YEAR

PATHOGEN CONTAMINANT

RESPIRATORY SECRETIONS Induced sputum : +bacteria, Mycoplasma, virus Culture, RT-PCR / Prospective cohort

69/76 [91%]

Honkinen M,2012

Sputum : +bacteria Culture / Prospective cohort

138/464 [29.7%]

Vong S,2013

Nasopharyngeal aspirate : +Mycoplasma p RT-PCR / Cross-sectional

24/166 [14.5%]

Medjo B,2014

Nasopharyngeal aspirate : +Mycoplasma p Loop-med isothermal amp ass / Cross-sectional

38/368 [10.3%]

Gotoh K,2012

Nasopharyngeal aspirate : bacteria, virus Multiplex PCR,Quick Ag,culture / Cross-sectional

38/45 [84.4%]

Chen Y,2012

Lung aspirate and pleural fluid : bacterial Culture / Cross-sectional

20/57 [38%]

Howie S,2014

PLEURAL FLUID Pleural fluid : +bacteria Culture / Retrospective cohort

79/288 [27.4%]

Deceuninck G, 2013

Pleural fluid : +bacteremia Culture / Cross-sectional

2/5 [40.0%]

Heine D,2013

BLOOD Blood : +bacteremia Culture / Meta-analysis

[5.14%,3.61-7.28%]

[14.7%]

CAP: severe vs less severe [p=.008]

Iroh Tam P,2015

Blood : +bacteremia Culture / Prospective cohort

27/862 [3.1%]

Vong S,2013


18/405 [4.4%]

22/405 [5%]

Chisti M ,2014


0/45 Chen Y,2012


2/171 [1.2%]

3/171 [1.8%]

Lai E,2014

Blood : +bacteremia Culture / Retrospective cohort

2/139 [1.4%]

3/139 [2.1%]

Parikh K,2014


26/369 [7%, 4.7–10.1%]

7/369 [1.8%]

Myers A,2013


53/288 [18.4%]

With empyema thoracis

Deceuninck G,2013


6/390 [1.5%]

9/390 [2.3%]

McCulloh R,2015

Blood : +bacteremia Culture / Cross-sectional

5/155 [3.2%]

1/155 [<1% ]

Heine D,2013

Blood : +bacteremia Culture / Cross-sectional

17/329 [5.1%]

16/329 [4.9%]

Real-time PCR from dried blood spot

Selva A,2013

Blood : +bacteremia Culture / Case control

2/82 [2.4%]

Ybanez S,2014

Blood : +Pneumococcal bacteremia Culture / Case control

1/73 [1.4%]

Complicated pneumococcal CAP vs control

(p=0.02)

Esposito S,2012

Blood : +Pneumococcal bacteremia PCR for Streptococcus pneumoniae / Case control

67/73 [91.8%]

19

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

66/164 [40.2%]

Diarrhea as comorbid illness

Chisti M,2012

Blood pH : metabolic acidosis [pH<7.0,HC03<24 mM, anion gap>16 mM] Case control

Total number of cases: 21

Wang L, 2013

Serum sodium : soidum <130 mm/L Cross-sectional

Total number of cases: 54

Consolidation by chest xray

Glatstein M,2014

Serum sodium : soidum <130 mm/L Cross-sectional

104/312 [33.3%]

Wrotek A,2013

Serum potassium : potassium <3.5 mMol/L Prospective cohort

51/180 [31%]

Diarrhea as comorbid illnes

Chisti M,2013

5. Clinically important endpoint: predictor of clinical outcome. DIAGNOSTIC AID : FINDINGS

STUDY DESIGN CLINICAL OUTCOME

RR or OR [95% CI] REMARKS P

VALUE AUTHOR/YEAR

Blood pH : metabolic acidosis [total serum CO2<17 mMol/L]

Case control

Mortality

Case fatality rate: 16% vs 5%

Comorbidity : diarrhea

0.039

Chisti M,2012

Blood pH : metabolic acidosis [pH<7.0,HC03<24 mM, anion gap>16mM]

Case control

8.50 [2.82-25.60]

0.001

Wang L,2013

Chest x-ray : bilateral multilobar infiltrates Retrospective cohort

ICU admission

6.6 [2.1-14.5]

McClain L,2014

Mechanical ventilation

3.0 [1.2-7.9]

Chest x-ray : unilateral multilobar infiltrates Retrospective cohort

ICU

admission

8.0 [2.9, 22.2]

Chest x-ray : moderate to large effusion Retrospective cohort

3.2 [1.1, 8.9]

Mechanical ventilation

14.8 [9.8-22.4]

Chest x-ray : pleural effusion Prospective cohort

Initial

treatment failure

14.10 [1.37-145.2]

0.03 Huang C,2013

Chest x-ray : consolidation Prospective cohort

0.56 [0.46-0.69]

<0.001 Basnet S,2015

Pulse oximetry : O2 sat<90% at room air Case control

2.40 [0.80-8.52]

0.03 Jain D,2013

Pulse oximetry : O2 sat <90% at room air Prospective cohort

1.91 [1.33-2.74]

<0.001 Basnet S,2015

White blood cell count : >17,500/mL Prospective cohort

2.42 [1.08-5.45]

0.03 Huang C,2013

White blood cell count : <4000 Case control

1.77 [0.6-5.7]

0.06 Jain D,2013

Blood culture : +bacteremia Case control

7.39 [2.44-22.43]

0.02

Hemoglobin : <10 g/dL Prospective cohort

2.38 [1.00-5.67]

0.05 Huang C,2013

Capillary blood glucose : <60 mg/dL Case control

1.33 [0.48-5.29]

0.14 Jain D,2013

C-Reactive protein : >40 mg/L Prospective cohort

1.01 [0.84-1.21]

0.918 Basnet S,2015

Serum sodium : hyponatremia Retrospective cohort

Prolonged

hospitalization

10.01 Wrotek A,2013

CRP : 7.5 mg/dL [median value] Retrospective cohort

1.03 [1.00-1.04]

Williams D,2015

Lung ultrasonography : impaired perfusion,

hypoechoic lesions with effusion Retrospective cohort

3.08 [1.15–8.29]

Lai S,2015 Pneumatocoele

risk 10.11

[2.95–34.64]

Pneumatocoele with subsequent

surgery

8.28 [1.86–36.93]

20

Clinical Question 5. WHEN IS ANTIBIOTIC RECOMMENDED?

SUBCOMMITTEE MEMBERS Cynthia Theresa M. Rimando Ernesto Z. Salvador

BACKGROUND 2012 2

nd 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]



21

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

COUNTRY

LABORATORY METHOD

POSITIVE YIELD [n] PER SAMPLE

[or SUBJECT] [N] n/N [%]

AGE

POSITIVE YIELD OF 1

PATHOGENS REQUIRING INITIAL ANTIBIOTIC

THERAPY n/N [%]

POSITIVE YIELD OF

VIRAL PATHOGEN n/N [%]

AUTHOR

YEAR

China Culture, molecular

1381/3181

0-16y 806/3181 [25%] 2375/3181 [75%] Wei L 2015

0-1y 716/1249 [57%] 1440/2375 [67%] 1-4y 451/1249 [37%] 744/2375 [31%] 4-6y 42/1249 [3%] 92/2375 [4%] 6-16y 40/1249 [3%] 99/237[4%]

Austria Culture, molecular

190/279 [68%] Adolescent Child

83/190 [34%] 107/190 [56%] Kurz H 2013

China Culture

1613/1613 [100%] Child 678/1613 [42%] 935/1613 [58%]2 Peng Y 2015

United States Culture, serology

1802/2222 [81%] <18y 330/1802 [18%] 1472/1802 [82%] Jain S 2015

Niger Molecular

138/1691 [8%] <5y 102/138 [74%] 126/138 [91%] Lagare A 2015

UK Culture, molecular, urine ag test, serology, immunofluorescence

214/401 [53%]

<16y

132/214 [62%]

82/214 [38%]

Elemraid M 2013

India Molecular

279/2345 [12%]

<12y

4.7y SD +1.9y

<5y

251/279 [90%] 28/279 [10%] Mathew J 2015

Finland Culture, molecular

74/76 [97%]

69 /74 [91%] 55/74 [72%] Honkinen M 2012

Nepal Culture

503/722 [70%]

290/503 [58%] 213/503 [42%] Banstola A 2013

Taiwan Culture, urine ag test, serology, virus isolation, immunofluorescence

209/245 [85%]

7m-16y

123/209 [59%]

86/209 [41%]

Chen C 2012

1Bacterial or codetection of bacterial and viral pathogens 2RSV

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

ODDS RATIO [95% CI]

YIELD [%]

p VALUE SPECIFICITY [95% CI]

AUTHOR YEAR

C-reactive protein [CRP] : >80 mg/L Bacterial/atypical vs viral pathogen Prospective cohort

3.6 [1.65–8.07]

0.001

Elemraid M 2014

C-reactive protein : elevated Pneumococcal vs viral pathogen Prospective cohort

19 [ 5-75]

Galetto-Lacour A 2013

C-reactive protein : elevated Bacterial vs viral pathogen Retrospective cohort

0.020

Hoshina T 2014

C-reactive protein : abnormal Mycoplasma p vs non-Mycoplasma p Cross-sectional

30.9 vs 23.7

0.002

Gao J 2015

C-reactive protein : > 200 ug/ml Bacterial pathogen Case control

56.10%

Huang H 2014

Procalcitonin : elevated Bacterial vs non-bacterial pathogen Prospective cohort

23 [5-117]

Galetto-Lacour A

2013

Procalcitonin : elevated Pneumococcal vs non-bacterial pathoge Retrospective cohort

0.0008

Hoshina T 2014

Lipocalin 2 : >130,1 Probable bacterial pathogen Case control

85.7%

Huang H 2014

Chest x-ray : presence of pneumonia Pneumococcal infection Cross-sectional

93% [80-98%]

Nascimento-Carvalho C 2015

White blood cell count : abnormal Mycoplasma p vs non-Mycoplasma p Cross sectional

65.5% vs

55.2%

0.001

Gao J 2015

White blood cell count : abnormal Bacterial vs non-bacterial pathogen Cohort

Not significant

Hoshina T 2014

White blood cell count : >15 × 109/L Bacterial vs viral pathogen Prospective cohort

0.5 [0.13–1.96]

0.320

Elemraid M

2014 Neutrophil count : >10 × 109 L / Bacterial vs viral pathogen Prospective cohort

5.9 [1.47–23.94]

0.012

Neutrophil count : abnormal Bacterial vs nonbacterial pathogen Cohort

Not significant

Hoshina T 2014

Neutrophil to lymphocyte ratio : 2.7 Bacterial vs viral pathogen Retrospective cohort

<0.001

Bekdas M

2014 CRP to mean platelet volume ratio: 11.0 Bacterial vs viral pathogen Retrospective cohort

<0.001

22

23

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].



24

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

METHOD STUDY DESIGN

AGE

+YIELD

%

Streptococcus pneumoniae

% [95% CI]

OTHER BACTERIA % [95%

CI]

ATYPICAL ORGANISM %

[95% CI]

AUTHOR

YEAR

Latin America and

Carribean Culture, PCR Meta-analysis

<5y

30.6%

11.08%

[7.63 -15.08]

Haemophilus influenzae: 3.64% [1.62–6.42]

Staphylococcus aureus: 3.44% [2.08–5.11]

Haemophilus influenzae b:3.08%[1.21–5.79]

Streptococcus pyogenes: 1.54%[0.49–3.15]

Mycoplasma pneumoniae 3.56% [0.99–7.64]

Chlamydia trachomatis 2.97% [0.74–6.60]

Chlamydia pneumoniae 2.60% [0.22–7.46]

Gentile A

2012

Cambodia Culture Cross-sectional

>5y

89.0%

17.7%

Haemophilus influenzae: 38.0% Klebsiella pneumoniae: 14.3% Pseudomonas aeruginosa:12.3% Bordetella pseudomallei: 9.3% Staphylococcus aureus: 3.7% Mycobacterium sp: 15.7%

Not determined

Vong S 2015

China Culture Cross-sectional

Child

50.2%

29.7% Hemophilus influenzae: 40.8% Moraxella catarrhalis: 7.3%

Mycoplasma pneumoniae 29.82%

Peng Y 2015

Finland Culture Cross-sectional

6m-15y

91%

50%

Hemophilus Influenzae: 38.0% Moraxelle catarrhalis: 28.0% Staphylococcus aureus: 13.0%

Mycoplasma pneumoniae 3.0%

Honkinen M 2012

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 2012 2013 2014 2015

Penicillin 8.0% 5.0% 7.0% 7.6% Chloramphenicol 8.7% 3.0% 4.0% 2.6% Cotrimoxazole 22.4% 20.0% 17.3% 16.5% Erythromycin 4.3% 6.0% 4.3 % 5.0% Azithromycin 0% - - - Sulbactam-ampicillin 6.7% - - - Ceftriaxone - 0% - 0% Levofloxacin - 2.0% - -

1.2.2. Haemophilus influenzae 2012 2013 2014 2015

Chloramphenicol 8.2% 7.0% 13.4% 5.7% Cotrimoxazole 34.1% 34.0% 42.9% 32.5% Ampicillin 16.7% 17.0% 12.0% 8.9% Amox/clavulanic - - 4.1% 5.2% Sulbactam-ampicilin - 7.0% - 3.4%

25

1.2.3. Staphylococcus aureus 2012 2013 2014 2015

Penicillin 95.4% 95.0% 95.5% 96.0% Oxacillin 54.9% 53.0% 60.3% 62.6% Vancomycin 0% 1.0% 0.9% 0.7% Clindamycin 8.4% 12.0% 11.0% 10.4% Erythromycin 10.9% 15.0% 12.0% 11.0% Rifampin - 1.0% 4.1% 4.9% Ciprofloxacin - 8.0% 7.4% 4.9% Cotrimoxazole 9.3% 14.0% 22.0% 25.9% Linezolid 1.6% 2.0% 1.2% 1.7%

1.2.4. Methicillin-resistant Staphylococcus aureus 2012 2013 2014 2015

Rifampin 7.7% 4.0% 6.0% 6.9% Vancomycin 0% 1.0% 1.0% 0.9% Clindamycin 13.4% 12.0% 14.% 14.0% Erythromycin - 15.0% 16.% 14.0% Ciprofloxacin 7.5% 7.0% 10.% 6.2% Cotrimoxazole 14.7% 18.0% 26.% 29.0% Linezolid 3.5% 1.0% 1.7% 2.2%

1.3. Clinical trials with clinical treatment failure, cure rate, relapse rate, adverse event, side effect readmission, ICU admission and clinical course as clinically important endpoints.

STUDY DESIGN

AGE

INTERVENTION

NUMBER

OF SUBJECTS

CLINICALLY IMPORTANT ENDPOINT

RESULTS AUTHOR

YEAR RISK or ODDS RATIO [95% CI]

p VALUE

REMARKS

Risk classification scheme: pCAP A or B

Subgroup in meta-analysis <18y

Azithromycin vs erythromycin

233 vs 133 Cure rate 1.22 [0.50-2.94]

Lodha R 2013

236 vs 156 Failure rate 0.73 [0.18-2.89] 84 vs 69 Side effects 0.92 [0.18-4.73]

Clarithromycin

vs erythromycin

124 vs 110 Cure rate 1.61 [0.86-3.08] 124 vs 110 Failure rate 0.52 [0.12-2.23] 121 vs 105 Relapse rate 0.17 [0.02-1.45] 133 vs 127 Adverse event 1.07 [0.60-1,90]

Azithromycin vs co-amoxiclav

125 vs 63 Cure rate 1.02 [0.54-1.95] 164 vs 112 Failure rate 1.21 [0.42-2.53] 164 vs 112 Side effect 0.15 [0.04-0.61]

Co-amoxiclav vs amoxicillin

50 vs 50 Cure rate 10.44 [2.85-38.21] 50 vs 50 Side effect 5.21 [0.24-111.24]

948 vs 839 Failure rate nonsevere CAP

1.18 [0.91-1.51]

203 vs 99 Failure rate severe CAP

1.71 [0.94-3.11]

Amoxicillin vs cefuroxime

42 vs 42 Cure rate 2.05 [0.18-23.51]

Amoxicillin vs chloramphenicol

923 vs 142 Failure rate 0.64 [0.41-1]

Cotrimoxazole vs chloramphenicol

55 vs 56 Cure rate 1.06 [0.47-2.40]

Amoxicillin vs clarithomycin

42 vs 40 Cure rate 1.05 [0.06-17.40]

Cefuroxime vs clarithromycin

42 vs 40 Cure rate 0.51 [0.04-5.89]

Cohort 1-18y

B-lactam monotherapy vs macrolide

1164 Treatment failure

Not significant

Ambroggio L 2015

RCT 6-59m

Amoxicillin 80 mkd

given TID

5d vs 10d Failure rate

p=0.16

40% vs 0% Greenberg

D 2014 3d vs 10d 0% vs 0%

RCT 11-59m

Amoxcillin 50 mkd

BID

3d vs 5d vs 7d

143

Failure rate

12.5% vs 15.0% vs 0%

Florendo S

2012

Risk classification scheme: pCAP C

Subgroup in meta- analysis <18y

Amoxicillin vs procaine penicillin

68 vs 86 Failure rate 0.75 [0.17-3.25]

Lodha R 2013

Cotrimozaxole vs procaine penicillin

349 vs 374 Cure rate 1.58 [0.26-9.69] 303 vs 311 Failure rate 1.72 [0.41-7.27]

Cotrimozaxole vs penicillin+ampicillin

66 vs 68 Cure rate 1.15 [0.36-3.61]

Chloramphenicol vs penicillin+gentamycin

559 vs 557 Adverse events 1.26 [0.96-1.66] 559 vs 557 Readmission < d 30 1.61 [1.02-2.55]

Chloramphenicol+ampicillin vs gentamycin

479 vs 47 Failure rate day 5 1.51 [1.04-2.19]

Chloramphenicol+penicillin vs ceftriaxone

46 vs 51 Cure rate 1.36 [0.47-3.93]

Ampicillin vs penicillin+chloramphenicol

52 vs 49 Cure rate 0.48 [0.15-15.1]

Benzathine penicillin vs procaine penicillin

135 vs 146 Cure rate 0.43 [0.27-1.01]

Penicillin+gentamycin vs co-amoxiclav

38 vs 33 Failure rate 0.86 [0.05-14.39] 55 vs 56 Relapse rate 1.02 [0.24-4.30]

Co-amoxiclav vs oxacillin+ceftriaxone

8/56 vs 7.48 Failure rate 0.98 [0.93-2.92]

Oral vs parenteral antibiotic for severe pneumonia

1982 vs 1960 Failure rate day 3 0.95 [0.78-1.15] 1948 vs 1922 Failure rate <5y 0.91 [0.76-1.09] 1048 vs 1028 Relapse rate 1.28 [0.34-4.82]

Cohort 2m-18y

Broad vs narrow spectrum antiobiotic

236 vs 256 Readmission within 7 days 0.25 Queen M

2014 Cohort <5y

Broad vs narrow spectrum antibiotic

13954 vs 1610

ICU admission 0.85 [0.27 -2.73] Wlliams D 2013

RCT 3m-2y

Ampicillin or penicillin vs cefuroxime

66 vs 253 Treatment failure 7.6% vs 4.7%

Dinur-Schejter Y 2013

Meta- analysis 3-59 m

Amoxicillin

vs standard IV antibiotic

12364

subjects

Treatment failure 2nd day

0.82 [0.55-0.82] Das R 2013 Treatment failure

6th day 0.92 [0.76-1.10]

Meta- analysis <18y

Amoxicillin vs procaine penicillin

68 vs 86

Failure rate

0.75 [0.17-3.25]

Lodha R 2013

Cohort 2m-11y

Penicillin G q 4 vs q6 120 vs 144 Final outcome No diffe- ference

Brandao A 2014

RCT 3-59m

Amoxicillin given at home then hosp vs at hosp alone

68 vs 86 Treatment failure HR 1.79 [1.30-2.46]

< 0.01 Patel A 2015

Cohort 1-17y

Ceftriaxone vs ceftriaxone+macrolide

4701 vs 8892

Transfer to ICU

> 2nd day

0.71 [Age:1-4y]

Leyenaar J 2014

0.14 [Age:5–17y]

Mortality

0.30 [Age:1-4y]

0.58 [Age:5–17y]

All-cause readmission

<30 days

0.10 [Age: 1-4y]

0.58 [Age:5–17y]

Pneumonia-related readmission <30 days

0.96 [Age:1-4y]

0.37 [Age:5–17y

Cohort 1-18y

Β-lactam+macrolide vs B-lactam monotherapy

2489 vs 18254

Readmission 0.69 (0.41-1.12) Ambroggio L 2013

RCT 3m–15y

Penicillin G vs IV cefuroxime 58 children Clinical course Not

significant Amarilyo G

2014

RCT <2y

Amoxicillin

vs benzyl penicillin

Treatment failure

7.7% vs

8.0% [per protocol analysis]

Agwayu A

2015

26

27

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].



28

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 RATE

% AUTHOR

YEAR <1y old 1-4y old >5y old

Perez C

2012

Cordillera

Administrative Region

Total 28.1% [106/377] RSV 60.3% 26.4% 0.94% Flu B 1.9% 2.8% 0.94% Flu A 0.94% 2.8% 0

Flu A [H1N1] 1.9% 0 0

Tacloban

Total 61.2% [501/819] Suzuki A

2012 Rhinovirus 30.5%

RSV 24.1% Adenovirus 4.0%

Flu A 2.2%

1.2. Global data

STUDY DESCRIPTION INCIDENCE

AUTHOR YEAR POOLED %[CI 95%]

I2 MIXED % [CI 95%]

I2 Data: worldwide from Apr 2000-Aug 2014 Study design: meta-analysis [21 studies, 10196 subjects]. PCR based

57.4 [50.8–64.1]

97.9

29.3 [22.4–36.2]

96.1

Wang M

2015

AREA Europe [12 countries] 61.7 [50.–70.3] 33.8 [18.0–49.5]

Asia [5 countries] 58.0 [47.1–68.8] 23.7 [15.8–31.5] Other areas [4 countries] 44.2 [34.6–53.8] 29.3 [23.0–35.6]

AGE ≤1 y old 76.1 [62.8–89.4] 95.1

2–5 y old 63.1 [50.2–75.9] 94.1 ≥6 y old 27.9 [4.3–51.5] 96.3

VIRAL ISOLATE

Rhinovirus 18.9 [14.3–23.4] RSV 17.5 [13.3–21.6]

Bocavirus 12.7 [8.5–16.9] Parainfluenza 7.8 [6.0–9.5]

Influenza 6.3 [4.7–8.0] hMetapneumovirus 6.1[ 4.1–8.1]

Adenovirus 6.0 [4.4–7.7] Coronavirus 3.9 [2.1–5.7]

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 ANALYSIS ENDPOINT ODDS or RISK RATIO

[95% CI] MEAN DIFFERENCE

[95% CI] AUTHOR

YEAR

Oseltamivir versus placebo

Meta-analysis

3 studies Risk for pneumonia 1.06 [0.62-1.83]

Jefferson T

2014

1 study Time to first symptom relief -29.40 [-47.04-11.76] 2 studies Serious adverse event 1.97 [0.59-6.56 ] 2 studies Vomiting 1.70 [1.23-2.35 ]

Zanamivir versus placebo

Meta-analysis

2 studies Risk for pneumonia 0.53 [0.12-2.38] 2 studies Time to first symptom relief -1.08 [-2.32-0.15] 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.

29

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 age- based 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].



30

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

N TIME TO RESOLUTION

Median (IQR) in hours, CI 95%]

AUTHOR YEAR

AGE

Cohort

334

<2y 2-4y 5-17 <2y 2-4y 5-17

Wolf R 2015

130 90 101

Single endpoint 1. Fever Temp: 36.0-37.9 101 61 63 14.5 (4.5-45.3) 18.4 (2.8-42.8) 10.6 (0.8-34)

2. Tachycardia Normal1

21 73 62 4.5 (0.3-18.4) 21.8 (5.7,-1.9) 18 (5.8-42.2) 3. Tachypnea 97 63 62 38.6 (18.7-68.9) 31.6 (9.5-61.9) 24.3 (10.8-59.2)

4; Needing O2 support None 90 58 61 39.5 (19.2-73.6) 44.2 (24-77.6) 38.3 (18-70.6) Multiple endpoints

1. Tachypnea + needing O2 support

Normal RR None

108 72 69 40.5 (20.1-75.0) 39.6 (15.6-79.2) 30.4 (14.7-59.2)

2. Tachypnea + tachycardia + needing O2 support

Normal RR,HR None

109 73 68 40.2 (19.5-73.9) 35.9 (15.9-77.6) 29.8 (17.2-56.6)

3. Tachypnea + fever + needing O2 support

Normal RR, none None

110 77 73 40.5 (20.7-70.1) 39.1 (18.4-77.6) 28.2 (14.7-44.7)

4.Tachypnea + tachycardia + fever + needing O2 support

Normal RR,HR None

110 72 71 40.5 (20.7-70.1) 39.7 (20.1-77.5) 29.2 (18.2-54)

1Based 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

N

STABILITY DEFINITION

N

TIME TO RESOLUTION

Median [50th percentile]

In hours

NUMBER OF SUBJECTS WITH PERSISTENT ABNORMALITY

BEYOND 48 HOURS

AUTHOR YEAR

DAY OF DISCHARGE

OPD VISIT AT DAY 14

Izadnegahdar R

2012

AGE Cohort

2174

<1y >1y <1y >1y <1y >1y <1y >1y

Single endpoint 1. Tachypnea Normal1 1703 1011 22 48 135 381 11 70

2. Fever Normal 629 12 15 0 3. O2 sat <92% Normal 192 10 31 0

1Based 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.

31

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 2012 2nd 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.


32

COUNTRY STUDY DESIGN

AGE GROUP

DESCRIPTION OF TREATMENT FAILURE

n/N RATE

[95% CI]

AUTHOR YEAR

pCAP C [or SEVERE PNEUMONIA]

Kenya Cohort 2-59m

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

3/169 1.8%

[0.4–5.1]

Agweyu A

2014

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)

42/453 12%

Webb C

2012

Nepal Cohort 2-35m

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.

209/610 35%

Basnet S 2015

pCAP D [or VERY SEVERE PNEUMONIA]

Kenya Cohort 2-59m

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 re-

duction 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.

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]

India Case control

3-59m

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

CONDITIONS ASSOCIATED WITH TREATMENT FAILURE AT LEAST 48 HOURS AFTER ADMISSION

n/N [RATE] AUTHOR YEAR

Clinician’s decision to change treatment in absence of criteria 54/100 (54.0%) Persistence of tachypnea, fever and indrawing 25/100 (25.0%)

Agweyu A 2014

Documented signs of deteriorating clinical status 12/100 (12.0%) Radiological findings informing change of treatment 2/100 (2.0%) Bacteriological findings informing change of treatment 1/100 (1.0%) Persistence of tachypnea or lower chest indrawing 10/31 (32.2%)

Jain D 2013

Empyema / pneumothorax 6/31 (19.3%) Hypoxemia [SaO2 <90%] 7/31 (22.5%) Persistence or new appearance of danger signs 5/31 (16.1%) Meningitis 2/31 (6.4%) Lung abscess 1/31 (3.2%)

48 hr after admission 5 days after admission

Webb C 2012

Worsening conscious level 4 ( 3.6%) 3 ( 5.0%) Worsening SaO2 19 (17.0%) 2 ( 3.0%) Persistent SaO2 <90% 0 19 (31.0%) Worsening respiratory rate 61 (55.0%) 12 (19.0%) Worsening temperature 22 (20.0%) 1 ( 2.0%) Persistent lower chest wall indrawing 0 31 (50.0%) New bacterial meningitis 2 ( 1.8%) 2 ( 3.0%) New renal impairment 0 1 ( 2.0%) New signs of shock 3 ( 2.7%) 4 ( 6.0%) New empyema 0 0 Admission to the intensive care unit 7/209 (3.34%)

Basnet S 2015

OR [95% CI]1 p VALUE

Nasopharyngeal aspirate positive for human metapneumovirus 2.34 (0.62- 8.81) 0.209 Nasopharyngeal aspirate positive for RSV 1.47 (0.91, 2.38) 0.115

SUMMARY OF EVIDENCE 1. Description of failure of standard treatment at 48 hours after admission

1Persistence 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

1Odds to having treatment failure

33

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.



SUMMARY OF EVIDENCE.

CAP SEVERITY STUDY DESIGN

AGE GROUP


RESULTS AUTHOR

YEAR Control group n=31

Switch therapy group n=26

p VALUE

Severe CAP RCT,

non-inferiority 1-60m

Mortality 0 0 - In-iw S 2015

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

34

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 D3 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 D3 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].


**Please see Methodology for description of grading of recommendation

35

SUMMARY OF EVIDENCE 1. Interventions that may be beneficial as an ancillary treatment



RESULTS AUTHOR

YEAR RISK or ODDS RATIO [95% CI]

p VALUE REMARKS

Intervention of proven benefit in pCAP C to reduce mortality. Zinc RCT, double-blind, placebo-controlled

Case fatality

0.33 [0.15-0.76] Srinivasan M 2012

Interventions of equal benefit in pCAP C to reduce treatment failure. O2 delivery: bubble CPAP vs low flow O2

RCT Treatment failure 0.27 [0.77-0.99] 0.0026 Trial stopped

earlier Chisti M

2015

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] 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

Length of stay 0.019 Justina M

2012 Spirulina RCT, open label

0.0006 Dioniso-Delfin T 2012

Zinc RCT Crackles score 0.034 Guinto, M

2014

2. Interventions requiring more studies to assess benefit as an ancillary treatment

Interventions in pCAP A or B. Cough preparation Meta-analysis Not improved 0.80 [0.38-1.67] Combined child

and adult Chang CC

2014 Steroid Retrospective cohort Treatment failure

2.38 [1.03-5.52] 0.04 [-] asthma hx Ambroggio L 2014 1.12 [0.43-2.92] 0.80 [+] asthma hx

Interventions in pCAP C. Steroid RCT, double-blind, placebo-controlled

Risk of readmission 0.46 Justina M 2012

Chest physiotherapy Meta-analysis

Length of stay

0.11-0.79 Chaves G 2013

Vitamin D Meta-analysis 0.29 Das R

2013

Zinc Meta-analysis

Pooled mean diff: -5.75

[-11.54-0.04]

Bernabe J 2012

Treatment failure

0.88 [0.71-1.10] Macalino M

2013

Zinc RCT, double-blind, placebo-controlled

1.3 [0.8-2.1]

Wadha N 2013

1.00 [0.68-1.50]

Sempe rtegu F 2012

0.423 Shah G 2012

Time to normalization of RR, temperature and SaO2

0.306 0.897 0.823

Srinivasan M 2012

Length of stay

0.05 Rulloda M 2012

0.193 Shah GS 2012

0.089 Low enrollment

Fataki M 2014

O2 delivery:bubble CPAP vs high flow O2

RCT, open label Treatment failure 0.50

[0.11-2.99] Trial stopped earlier

Chisti M 2015

Virgin coconut oil RCT

Length of stay

0.336 Vierneza M 2012

Probiotic RCT Mean:

3.2d vs 3.3d Becina P

2014 Oral folate RCT, placebo-controlled Mean:

4.0d vs 4.8d Villanueva J

2013 Vitamin D3

RCT Not

significant Mondragon A

2014 Nebulization: acetylcysteine vs saline RCT Mean:

2.5d vs 2.9d Martinez M

2012 Nebulization: saline or bronchodilator Cross-sectional Not

significant Delizo M

2014

36

BURDEN SITE STUDY PERIOD

AGE GROUP

AVERAGE NUMBER PER YEAR

MEAN RATE SOURCE

MORBIDITY Acute lower respiratory infection and pneumonia

Nationwide

2012-14 <5y 286 073 Department 1

5-14y 326,326 Hosp for pneumonia

ICD code 10 18.0,18.9, 18.91, 18.92,18.93

2012-15

28d-19y

242,086

7.9%2

Philippine Pediatric

Society,Inc3

MORTALITY Pneumonia-related.

ICD code 10 J18.0,18.9, 18.91, 18.92,18.93

Nationwide

2.26%4

Philippine Pediatric

Society,Inc3

Pneumonia-related Worldwide 2000-13 <5y 0.935 [UR5 0.817-1.057] 14.9% [UR5 13.0-16.8] Liu L,2014

ECONOMIC BURDEN6

PNEUMONIA SEVERITY STUDY PERIOD AGE

GROUP ESTIMATED TOTAL HEALTH CARE COST7

Moderate risk 2012

Adult

PhP 8.48 billion Mendoza B 2015 High risk PhP 643.76 million

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]


**Please see Methodology for description of grading of recommendation

SUMMARY OF EVIDENCE 1. Rationale for prevention: burden of illness

of Health

12012, 2013, and 2014 Annual Reports Field Health Services Information System Department of Health. 2Rate = discharges due to pneumonia / total number of discharges from Jan 1, 2012 to December 31, 2015. 3ICD 10 Registry, Committee on Registry of Childhood Disease, Philippine Pediatric Society, Inc. 4Rate = deaths due to pneumonia / total number of discharges due to pneumonia from Jan 1, 2012 to December 31, 2015. 5UR – uncertainty range 6Gap in knowledge: no available data exclusive for children. 7Estimated mean value based on Philippine Health Insurance claims and estimated healthcare cost.

37


COUNTRY AGE


RESULTS AUTHOR

YEAR RISK, HAZARD or ODDS RATIO [95% CI] REMARKS

Intervention of proven benefit: vaccination

PCV 13 Time-trend analysis

USA <18y

CAP 43.2% vs 39.2%, p=0.005 Moore M 2015

All-cause CAP hosp 17-21% reduction in <5y Simonsen L 2014 Empyema 37-50% reduction in <18y

Uruguay <14y

CAP hosp

All-cause 78.1% reduction Pirez M 2013 Pneumoccous 92.4% reduction

Argentina <5y

Radiologic CAP hospitalization

20.1 [13.1-26.4], p<0.001 Gentile A 2015

Alaska <5y

Pneumococcal CAP hospitalization

57% reduction Bruce M 2015

PCV 13 Cohort

USA <2y All-cause CAP

hospitalization 27% reduction

Griffin M 2014

PCV 7-13 Time-trend analysis

England <2y

CAP hospitalization No difference Saxena S 2015 Empyema 0.58 [0.34-0.99]

PCV 7-13 Time-trend analysis

Israel <5y

Annual incidence of alveolar pneumonia

68% decline in OPD visits 32% decine in hospitalization

Greenberg D 2015

PCV 7-13 Cohort

Italy <5y

Pneumococcal CAP hospitalization

0.43 [0.21-0-90]

Martinelli D 2013

PCV 10 Time-series analysis

Brazil <2y

All-cause CAP hospitalization

23-28% reduction Afonso E 2013

PCV 10 Cross-sectional

Brazil <2y

CAP prevalence 40% reduction Abrao MA 2015

PCV 10 RCT,double-blind

South America Children

Consolidation CAP Vaccine efficacy: 23.4% [8.8-35.7]

Tregnaghi M

Adverse events 21.5%(20.7-22.2) vs 22.6% (21.9-23.4)

Hib vaccine Time-series analysis

Vietnam <5y

Radiologic CAP 39% reduction Flasche S 2014

2. Interventions that may be beneficial to prevent pneumonia, or reduce pneumonia-related morbidity and mortality

2014

Interventions of potential benefit Risk for CAP: Firewood,charcoal use Cross-sectional

Kenya Children

Nonsevere CAP 4.2 [3.9-4.6] Ekaru H 2012 Severe CAP 1.1 [1.02-1.26]

Risk for CAP: smoker Case control

New Zealand <5y CAP 1.99 [1.05-3.81] Grant V

2012

Philippines <2y

Severe CAP 2.60 [1.57-4.30]

Tomas A 2012-2015

Protective against CAP:1.breastfeeding >3m 2.no smokers

Case control

Brazil

6m-13y

Association with hospitalization

for CAP

[-] association

Barsam F

2013

Protective against CAP: breastfeeding Cohort

Kenya Infants

First physician diagnosed pneumonia

0.53 [0.39-0.73) 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]

Children

Acute lower respiratory infection [ALRI] severity

[+] association between Vit D deficiency and

increasing severity of ALRI

Larkin A

2014

Zinc Meta-analysis

[3 studies]

Preschool children

Pneumonia-related mortality

0.52 [0.11-2.39] Fu W

2013

38

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7 Medjo B, Atanaskovic-Markovic M, Radic S, Nikolic D, Lukac M, Djukic S.: Mycoplasma pneumoniae as a causative agent of community- acquired pneumonia in children.: clinical features and laboratory diagnosis. Ital J Pediatr 2014;18;104:1-7

8 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.

9 Krenke K, Sanocki M, Urbankowska E, Kraj G, Krawiec M, Urbankowski T, Peradzyńska J, Kulus M.: Necrotizing Pneumonia and Its Complications in Children Adv Exp Med Biol. 2015;857:9-17.doi:10.1007/5584_2014_99.

10 Lai S, Wong K, Liao S.: Value of Lung Ultrasonography in the Diagnosis and Outcome Prediction of Pediatric Community-Acquired Pneumonia with Necrotizing Change. PLoS One 2015;10:e0130082. doi: 10.1371/journal.pone.0130082.eCollection 2015.

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11 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.

12 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.

13 Gotoh K, Nishimura N, Ohshima Y, Arakawa Y, Hosono H, Yamamoto Y, Iwata Y, Nakane K, Funahashi K, Ozaki T.: Detection of Mycoplasma pneumoniae by loop-mediated isothermal amplification (LAMP) assay and serology in pediatric community-acquired pneumonia. J Infect Chemother 2012;18:662-7.doi: 10.1007/s10156-012-0388-5.

14 Chen Y, Liu P, Huang Y, Chen C, Chiu L, Huang N, Hsieh K, Chen Y.: Comparison of diagnostic tools with multiplex polymerase chain reaction for pediatric lower respiratory tract infection: a single center study. J Microbiol Immunol Infect 2013;46:413-8. doi:10.1016/j.jmii.2012.07.016.

15 Howie S, Morris G, Tokarz R, Ebruke B, Machuka E, Ideh R, Chimah O, Secka O, Townend J, Dione M, Oluwalana C, Njie M, Jallow M, Hill P, Antonio M, Greenwood B, Briese T, Mulholland K, Corrah T, Lipkin W, Adegbola R.: Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples. Clin Infect Dis 2014;59:682-5.doi:10.1093/cid/ciu384.

16 Deceuninck G, Quach C, Panagopoulos M, Thibeault R, Côté-BoileauT, Tapiéro B, Coïc L, De Wals P, Ovetchkine P.: Pediatric Pleural Empyema in the Province of Quebec: Analysis of a 10-Fold Increase Between 1990 and 2007. J Pediatric Infect Dis Soc 2014;3:119-26. doi:10.1093/jpids/pit075.

17 Heine D, Cochran C, Moore M, Titus M, Andrews A.: The prevalence of bacteremia in pediatric patients with community-acquired pneumonia: guidelines to reduce the frequency of obtaining blood cultures. Hosp Pediatr 2013;3:92-6.

18 Iroh Tam P, Bernstein E, Ma X, Ferrieri P.: Blood Culture in Evaluation of Pediatric Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Hosp Pediatr 2015;5:324-36.doi:10.1542/hpeds.2014-0138.

19 Chisti M, Graham S, Duke T, Ahmed T, Ashraf H, Faruque A, Vincente S, Banu S, Raqib R, Salam M.: A Prospective Study of the 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? Indian J Pediatr 2015;82:439-44

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: Bacteremic pneumococcal community-acquired pneumonia in children less than 5 years of age in Italy. Pediatr Infect Dis J 2012;31:705-10.

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 acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia. PLoS One. 2012;7:e39164.

28 Wang L, Mu S, Lin C, Lin M, Sung T.: Fatal community-acquired pneumonia: 18 years in a medical center. Pediatr Neonatol 2013;54:22-7. 29 Glatstein M, Rozen R, Scolnik D, Rimon A, Grisaru-Soen G, Freedman S, Reif S.: Radiologic predictors of hyponatremia in children

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 C-

Reactive 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.

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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 community- acquired pneumonia in children. Pediatr Infect Dis J 2013;32:1175-9.doi:10.1097/INF.0b013e31829ba62a.

14 Hoshina T, Nanishi E, Kanno S, Nishio H, Kusuhara K, Hara T.: The utility of biomarkers in differentiating bacterial from non-bacterial lower respiratory tract infection in hospitalized children: difference of the diagnostic performance between acute pneumonia and bronchitis. J Infect Chemother 2014;20:616-20. doi:10.1016/j.jiac.2014.06.003.

15 Gao J, Yue B, Li H, Chen R, Wu C, Xiao M.: Epidemiology and clinical features of segmental/lobar pattern Mycoplasma pneumoniae pneumonia: A ten-year retrospective clinical study. Exp Ther Med 2015;10:2337-2344.

16 Nascimento-Carvalho C, Araújo-Neto C, Ruuskanen O.: Association between bacterial infection and radiologically confirmed pneumonia among children. Pediatr Infect Dis J 2015;34:490-3.doi:10.1097/INF.0000000000000622.

17 Bekdas M, Goksugur S, Sarac E, Erkocoglu M, Demircioglu F.: Neutrophil/lymphocyte and C-reactive protein/mean platelet volume ratios in differentiating between viral and bacterial pneumonias and diagnosing early complications in children. Saudi Med J 2014;35:442-7.

Clinical Question 6. What empiric treatment should be administered if a bacterial etiology is strongly considered?

1 Gentile A, Bardach A, Ciapponi A, Garcia-Marti S, Aruj P, Glujovsky D, Calcagno J, Mazzoni A, Colindres R.: Epidemiology ofcommunity- acquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis. Int J Infect Dis 2012;16:e5- 15. doi:10.1016/j.ijid.2011.09.013.

2 Vong S, Guillard B, Borand L, Rammaert B, Goyet S, Te V, Try P, Hem S, Rith S, Ly S, Cavailler C, Mayaud C, Buchy P.: Acute lower respiratory infections in ≥5 year-old hospitalized patients in Cambodia, a low-income tropical country: clinical characteristics and pathogenic etiology. BMC Infectious Diseases 2013 13:97.

3 Peng Y, Shu C, Fu Z, Li QB, Liu Z, Yan L.:Pathogen detection of 1 613 cases of hospitalized children with community acquired pneumonia. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:1193-9.

4 Honkinen M, Lahti E, Österback R, Ruuskanen O, Waris M.Viruses and bacteria in sputum samples of children with community-acquired pneumonia. Clin Microbiol Infect. 2012;18:300-7.doi:10.1111/j.1469-0691.2011.03603.

5 Antimicrobial Resistance Surveillance Reference Laboratory, Antimicrobial Resistance Surveillance Program 2012 Annual Report. Manila, Philippines;2012.




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.

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19 Leyenaar J, Shieh M, Lagu T, Pekow P, Lindenauer P.: Comparative effectiveness of ceftriaxone in combination with a macrolide compared with ceftriaxone alone for pediatric patients hospitalized with community-acquired pneumonia. Pediatr Infect Dis J 2014;33:387-92. doi: 10.1097/INF.0000000000000119.

20 Amarilyo G, Glatstein M, Alper A, Scolnik D, Lavie M, Schneebaum N, Grisaru-Soen G, Assia A, Ben-Sira L, Reif S.: IV Penicillin G is as effective as IV cefuroxime in treating community-acquired pneumonia in children. Am J Ther 2014;21:814.doi:10.1097/MJT. 0b013e3182459c28.

21 Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M. Severe Pneumonia Study Group. Collaborators.: Aweyo F, Awuonda B, Chabi M, Isika N, Kariuki M, Kuria M, Mandi P, Masibo L, Massawa T, Mogoa W, Mutai B, Muriithi G, Ng'arng'ar S, Nyamai R, Okello D, Oywer W, Wanjala L.: Oral amoxicillin versus benzyl penicillin for severe pneumonia among Kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis 2015;60:1216-24. doi: 10.1093/cid/ciu1166.

Clinical Question 7. What treatment should be initially given if a viral etiology is strongly considered?

1 American Academy of Pediatrics, Committee on Infectious Diseases: Recommendations for prevention and control of influenza in children, 2015–2016. Pediatrics 2015;136(4).doi:10.1542/peds.2015-2920.

2 Jefferson T, Jones M, Doshi P, Del Mar C, Hama R, Thompson M, Spencer E, Onakpoya I, Mahtani K, Nunan D, Howick J, Heneghan C.: Neuraminidase inhibitors for preventing and treating influenza in adults and children (Review). Cochrane Database Syst Rev 2014;4:CD008965.

3 Kimberlin D, Acosta E, Prichard M, Sanchez P, Ampofo K, Lang D, Ashouri N, Vanchiere J, Abzug M, Abughali N, Caserta M, Englund J, Sood S, Spigarelli M, Bradley J, Lew J, Michaels M, Wan W, Cloud G, Jester P, Wakeman F and Whitley R, for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.: Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza. J Infect Dis. 2013;207(5): 709–720. doi: 10.1093/infdis/jis765.

4 Perez C.: Prevalence of viral pathogens among paediatric patients admitted for pneumonia in a local tertiary hospital. Pediatric Infectious Disease Society of the Philippines Journal 2012;13:8-14.

5 Suzuki A, Lupisan S, Furuse Y, Fuji N, Saito M, Tamaki R, Galang H, Sombrero L, Mondoy M, Aniceto R, Olveda R, Oshitani H.: Respiratory viruses from hospitalized children with severe pneumonia in the Philippines. BMC Infect Dis. 2012;12:267.doi: 10.1186/1471-2334-12-267.

6 Wang M, Cai F, Wu X, Wu T, Su X, Shi Y.: Incidence of viral infection detected by PCR and real-time PCR in childhood community- acquired pneumonia: A meta-analysis. Respirology 2015; 20: 405-412. doi: 10.1111/resp.12472.

7 Self W, Griffin M, Zhu Y, Dupont W, Barrett T, Grijalva C.: The high burden of pneumonia on US emergency departments during the 2009 influenza pandemic. J Infect. 2014; 68(2):156-64. doi:10.1016/j.jinf.2013.10.005.

Clinical Question 8. When can a patient be considered as responding to the current antibiotic?

1 Wolf R, Edwards K, Grijalva C, Self W, Zhu Y, Chappell J, Bramley A, Jain S, Williams D.:Time to clinical stability among children hospitalized with pneumonia. J Hosp Med 2015;10:380-3. doi: 10.1002/jhm.2370.

2 Izadnegahdar R, Fox M, Thea D, Qazi S.: Pneumonia Studies Group. Frequency and trajectory of abnormalities in respiratory rate, 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.

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8 Ambroggio L, Test M, Metlay J, Graf T, Blosky M, Macaluso M, Shah S.: Adjunct Systemic Corticosteroid Therapy in Children With Community-Acquired Pneumonia in the Outpatient Setting. J Pediatric Infect Dis Soc 2015 ;4:21-7. doi:10.1093/jpids/piu017.

9 Chaves G, Fregonezi G, Dias F, Ribeiro C, Guerra R, Freitas D, Parreira V, Mendonca K.: Chest physiotherapy for pneumonia in children. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD010277. DOI: 10.1002/14651858.CD010277.pub2.

10 Das R, Singh M, Panigrahi I, Naik S.: Vitamin d supplementation for the treatment of acute childhood pneumonia: a systematic review. ISRN Pediatr. 2013;2013:459160. doi: 10.1155/2013/459160. eCollection2013.

11 Doctor-Bernabe J, Ampil I, Bibera G.: Effect of zinc supplementation as an adjunct in the treatment of pneumonia in children ages 2 to 59 months: a meta-analysis. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

12 Macalino MV, Dans L, Lorenzana R.: Zinc as adjunct to antibiotics in the treatment of severe pneumonia in children aged two months to five years: a meta-analysis. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

13 Wadhwa N, Chandran A, Aneja S, Lodha R, Kabra S, Chaturvedi M, Sodhi J, Fitzwater S, Chandra J, Rath B, Kainth U, Saini S, Black R, Santosham M, Bhatnagar S.: Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2013;97:1387-94.doi:10.3945/ajcn.112.052951.

14 Sempértegui, Estrella B, Rodríguez O, Gómez D, Cabezas M, Salgado G, Sabin L, Hamer D.: Zinc as an adjunct to the treatment of severe pneumonia in Ecuadorian children: a randomized controlled trial. Am J Clin Nutr 2014;99:497-505.doi: 10.3945/ajcn.113.067892.

15 Shah G, Dutta A, Shah D, Mishra O.: Role of zinc in severe pneumonia: a randomized double bind placebo controlled study. Ital J Pediatr 2012;38:36. doi: 10.1186/1824-7288-38-36.

16 Srinivasan M, Ndeezi G, Mboijana C, Kiguli S, Bimenya G, Nankabirwa V and Tumwine J.: Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial. Medicine 2012;10:14.

17 Fataki M, Kisenge R, Sudfeld C, Aboud S, Okuma J, Mehta S, Spiegelman D, Fawzi W.: Effect of zinc supplementation on duration of hospitalization in Tanzanian children presenting with acute pneumonia. J Trop Pediatr 2014;60:104-11.doi:10.1093/tropej/fmt089.

18 Becina P, Peralta K, Becina G.: A double-blind, randomized, controlled trial of the efficacy of multiple strain probiotics as adjunct therapy for patients [2 months-4 years old] with moderate risk community-acquired pneumonia admitted at National Children’s Hospital. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

19 Villanueva J, Matheus J.: A randomized controlled trial on the effects of oral folate in the treatment of pediatric community-acquired pneumonia-c among infants ages 2-12 months admitted at the pediatric ward of Dr. Jose Fabella Memorial Hospital. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

20 Mondragon A.: The efficacy of oral vitamin D3 supplementation on the severity of pneumonia in children ages 3 months – 60 months: a randomized double-blind controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

21 Martinez M.:The efficacy of acetylcysteine nebulization as an adjunct therapy for community-acquired pneumonia-C in children aged 3 to 60 months admitted at a tertiary government hospital. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

22 Delizo M, Resurreccion E.: Nebulization using normal saline solution or bronchodilators as adjunct treatment in children hospitalized with community-acquired pneumonia: a retrospective study Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

23 Dalangin B.: A randomized controlled trial on the efficacy and safety of probiotic [Bacillus claushii] and zinc as adjuncts in the treatment of pediatric community-acquired pneumonia among 1 to 10 years old in an outpatient department at a private hospital. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

24 Dionisia-Delfin,T.:The effectiveness of spirulina as an adjunct in the treatment of pediatric community-acquired pneumonia C among children aged 2-5 years: a randomized placebo controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

25 Vierneza M.: The effectiveness of virgin coconut oil as adjunct treatment of pediatric community acquired pneumonia: a randomized controlled trial. Philippine Pediatric Society, Inc. Abstracts Philippine Pediatric Researches 2012-2015.

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.



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/S2213- 2600(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.

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12 Martinelli D, Pedalino B, Cappelli M, Caputi G, Sallustio A, Fortunato F, Tafuri S, Cozza V, Germinario C, Chironna M, Prato R; Apulian Group for the surveillance of pediatric IPD.: Towards the 13-valent pneumococcal conjugate universal vaccination: effectiveness in the transition era between PCV7 and PCV13 in Italy, 2010-2013. Hum Vaccin Immunother 2014;10:33-9. doi:10.4161/hv.26650.

13 Saxena S, Atchison C, Cecil E, Sharland M, Koshy E, Bottle A.: Additive impact of pneumococcal conjugate vaccines on pneumonia and empyema hospital admissions in England. J Infect 2015;71:428-36. doi: 10.1016/j.jinf.2015.06.011.

14 Griffin M, Mitchel E, Moore M, Whitney C, Grijalva C; Centers for Disease Control and Prevention (CDC).: Declines in pneumonia hospitalizations of children aged <2 years associated with the use of pneumococcal conjugate vaccines -Tennessee,1998-2012. MMWR Morb Mortal Wkly Rep. 2014;63:995-8

15 Greenberg D, Givon-Lavi N, Ben-Shimol S, Ziv JB, Dagan R.: Impact of PCV7/PCV13 introduction on community-acquired alveolar pneumonia in children <5 years. Vaccine 2015;33(36):4623-9. doi: 10.1016/j.vaccine.2015.06.062.

16 Abrão W, de Mello L, da Silva A. Nunes A.: Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious respiratory diseases and hospitalization rates in children. Rev Soc Bras Med Trop 48:44-49.

17 Afonso E, Minamisava R, Bierrenbach A, Escalante J, Alencar A, Domingues C, Morais-Neto O, Toscano C, Andrade A.: Effect of 10- valent pneumococcal vaccine on pneumonia among children. Brazil Emerg Infect Dis 2013;19:589-97. doi:10.3201/eid1904.121198.

18 Tregnaghi M, Sáez-Llorens X, López P, Abate H, Smith E, Pósleman A, Calvo A, Wong D, Cortes-Barbosa C, Ceballos A, Tregnaghi M, Sierra A, Rodriguez M,Troitiño M, Carabajal C, Falaschi A, Leandro A, Castrejón M, Lepetic A, Lommel P, Hausdorff WP, Borys D, Ruiz Guiñazú J, Ortega-Barría E, Yarzábal JP, Schuerman L; COMPAS Group.: Efficacy of pneumococcal nontypable Haemophilus influenza 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.1440- 1754.2011.02244.x.

22 Tomas A, Resurreccion M.: A hospital based case control study on the association of selected maternal risk taking behaviors in the 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/s00431-012-1909-z.

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 Meta- Analysis 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

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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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2004 SUMMARY RECOMMENDATION.

An antibiotic is recommended

CQ 5. WHEN IS ANTIBIOTIC RECOMMEDED

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].


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?


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.


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?

1. Among inpatients, oxygen and hydration should be given if needed [Recommendation Grade D]. 2. Cough preparations, chest physiotherapy, bronchial hygiene, nebulization using normal saline solution, steam inhalation, topical

solution, bronchodilators and herbal medicines are not routinely given in community-acquired pneumonia [Recommendation Grade D]. 3. In the presence of wheezing, a bronchodilator may be administered [Recommendation Grade D].


1. 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?

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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