86323517 PCAP Updates

______________________________________________________________

An Official Publication of the

Philippine Academy of Pediatric Pulmonologists, Inc.

______________________________________________________________

PAPP PERSPECTIVE

Updates

in the

Evaluation and Management of

Pediatric Community-Acquired Pneumonia

PAPP Task Force on pCAP [2008]

2

Philippine Academy of Pediatric Pulmonologists, Inc. [PAPP, Inc.] 2008

All rights reserved. Publication and request for permission to reproduce can be

obtained from the Philippine Academy of Pediatric Pulmonologists, Inc., Room

102 GJ Building, 385 Quezon Avenue Quezon City Telefax No +632 3747201;

email: [email protected].

This document is not intended to be a standard of care. The responsibility for its

use lies with the reader. In no event shall PAPP, Inc. be liable for damages arising

from its use.

PAPP Officers

Olivia C. Go, MD FPPS FPAPP……………….…President

Arnel Gerald Q. Jiao, MD FPPS FPAPP…….…...Vice-President

Cesar M. Ong, MD FPPS FPAPP………………...Secretary

Maria Nerissa A. de Leon, MD FPPS FPAPP…....Treasurer

Mary Therese M. Leopando, MD FPPS FPAPP….Director

Clara R. Rivera, MD FPPS FPAPP……………….Director

Mary Ann F. Aison, MD FPPS FPAPP…………...Director

PAPP Task Force on pCAP

Cristan Q. Cabanilla, MD FPPS FPAPP

Chair

Regina M. Canonizado, MD FPPS FPAPP

Anjanette R. de Leon, MD DPPS DPAPP

Roslyn Marie K. Dychiao, MD FPPS DPAPP

Beatriz Praxedes Apolla I. Mandanas-Paz, MD DPPS DPAPP

Anna Marie S. Putulin, MD FPPS FPAPP

Emily Dolores G. Resurreccion, MD FPPS FPAPP

Ana Maria A. Reyes, MD FPPS FPAPP

Marion O. Sanchez, MD DPPS DPAPP

Rita Marie Lourdes S. Vergara, MD FPPS FPAPP

Rozaida R. Villon, MD FPPS FPAPP

Members

Gerardo L. Beltran, MD FPCR

Guest Radiologist

Gladys L. Gillera, MD DPPS DPAPP

Secretary�

mailto:[email protected]

3

CONTENTS

Foreword

Preface to the Updates and Acknowledgement

2004 Clinical Practice Guideline

Clinical Questions with Recommendations, and

Update Highlights with Annotations

Appendix

Bibliography

4

FOREWORD

In the past years, we witnessed a major revolution in the science and practice of pediatric

pulmonary medicine, more particularly in our concept and management of pneumonia in children.

We are challenged to adopt and apply these newer insights about the disease in dealing with our

patients.

Despite the inadequate and limited advancement in medical technology among

developing countries, we are able to establish the diagnosis of pneumonia and manage it

comprehensively largely based on good clinical acumen. Furthermore, our knowledge in clinical

epidemiology is imperative to facilitate its holistic management, while the rational use of

antimicrobial agents increases our awareness on the emergence of drug resistance in specific

localities.

This clinical update on pneumonia contains a comprehensive evidence-based review of

national as well as international researches that depicts the current clinical practice and

management strategies adopted to contain the disease. The Academy maintains its primary

purpose to apprise our pediatric practitioners of the many medical investigations on pneumonia

and propose practical treatment options to combat the disease.

This current issue does not intend to replace the 2004 PPS Clinical Practice Guideline in

the Management of Pediatric Community-Acquired Pneumonia. This is simply presented to

clarify some gaps in the knowledge stated therein. We look forward that this understanding

bridges the small differences in our daily practice to bring forth a worthy clinical outcome.

Allow me to take this good opportunity to congratulate the Task Force on PCAP for such

an excellent job.

Olivia C. Go, MD

President

Philippine Academy of Pediatric Pulmonologists, Inc.

5

PREFACE TO THE UPDATES

One of the issues that was raised regarding the 2004 Clinical Practice Guideline in the

Evaluation and Management of Pediatric Community-Acquired Pneumonia is the gap in

knowledge underscored in each recommendation. To address this concern, the Task Force on

pCAP has reviewed data available from local and foreign literature. As this manuscript is merely

an update consisting of recent literature, it is not intended to be a standard of care much more a

revision of the current guideline.

This update is available in two formats. The abbreviated format consists of update

highlights and summary of recent evidence. This is made available as a limited service item in the

form of hard copy during the 2008 16th PAPP Annual Convention. The complete version which

includes not only similar highlights but detailed description of each update can be downloaded

from the Philippine Academy of Pediatric Pulmonologists, Inc. through the website of the

Philippine Pediatric Society www.pps.org.ph. The reader is encouraged to access the complete

version for a more thorough discussion.

Cristan Q Cabanilla, MD

Chair

Task Force on pCAP

Acknowledgement

This manuscript is the result of a concerted effort by the Task Force on pCAP

under the leadership and guidance of the PAPP officers headed by Olivia C. Go.

Special gratitude is due to Luis M. Rivera Sr., Alexander O. Tuazon, Milagros S.

Bautista and Agnes R. Mendoza for reviewing the document.

http://www.pps.org.ph/

6

2004 CLINICAL PRACTICE GUIDELINE

CLINICAL QUESTIONS WITH RECOMMENDATIONS, AND

UPDATE HIGHLIGHTS WITH ANNOTATIONS

Clinical Questions [CQ]

Evaluation

1. Who shall be considered as having community-acquired pneumonia?

2. Who will require admission?

3. What diagnostic aids are initially requested for ambulatory patients?

4. What diagnostic aids are initially requested for in-patients?

Treatment

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

antibiotic?

9. What should be done if a patient is not responding to current

antibiotic therapy?

10. When can switch therapy in bacterial pneumonia be started?

11. What ancillary treatment can be given?

Prevention

12. How can pneumonia be prevented?

7

INTRODUCTION

The world incidence of lower respiratory tract infection that includes pneumonia

in developing countries has been recently estimated to be 150.7 million cases, 95% of

whom are under five years of age, and 13% severe enough to require hospital admission

[Rudan I,2004]. In the Philippines, it continues to be a leading cause of morbidity in

children accounting to about 828.8 per 100,000 population [Department of Health Field Health

Service Information System, 2006].

Estimates of treatment cost highlight the economic burden that childhood

pneumonia places on health care systems. An average cost of treatment for acute

respiratory infection per episode from the perspective of developing economies in Asia

ranged from USD 1.70 in a primary health care setting to USD 155.30 for hospitalized

care [Toan NV,2001; Rattanadilok N,2002]. Outpatient and hospitalized care of a child with

pneumonia have been estimated to be USD 13.44 and USD 71.0 per episode, respectively

[Hussain H, 2006]. An average parent’s total household expenses for a child’s admission

because of pneumonia have been found to be 5 to 11% of an average net income per

family in Israel [Shoham Y,2005]. In the local setting as provided by the National Health

Insurance Program, the 2006 total payment claims for pneumonia [ICD-10 Code J18.9]

below 19 years of age amounted to PhP 324.688 M [Philippine Health Insurance Corporation,

Claims Payment Summary for CY 2006 Ages 0-19 for Pneumonia,2007].

One public health strategy to address this continuing concern is the

implementation of a clinical practice guideline. In 2004, the Philippine Pediatric Society,

the Philippine Academy of Pediatric Pulmonologists and the Pediatric Infectious Disease

Society of the Philippines came out with a clinical practice guideline in the evaluation

and management of pediatric community-acquired pneumonia. In 2006, the Philippine

Health Insurance Corporation has adopted the document as one of the guidelines that can

serve as a basis for quality assurance and accreditation [PhilHealth Health Technology

Assessment Unit, Quality Assurance Research and Policy Development Group,2006]. Its acceptability

and utilization have been subsequently assessed. Of the 166 respondents to a random

sampling questionnaire survey conducted during the 2006 43rd PPS Annual Convention,

82% acknowledged applying the recommendation in their practice [Cabanilla C, Santos J,

2006]. In another survey among 61 pediatric consultants and residents from MetroManila,

about 96% confirmed that such guideline was being followed [de Jesus-Oabel BA and Atienza-

de Leon MN, 2007].

This update presents evidences based on recent local and foreign literature dealing

with the recognition of community-acquired pneumonia in an immunocompetent patient

aged 2 months to 19 years, identification of appropriate and practical diagnostic

procedures, and initiation of rational management and preventive measures

8

CQ 1. Who shall be considered as having community-acquired pneumonia?

2004 Clinical Practice Guideline 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 [Grade B].

2. for ages 5 to 12 years are fever, tachypnea, and crackles [Grade D].

3. beyond 12 years of age are the presence of the following features [Grade D]:

a. fever, tachypnea, and tachycardia; and

b. at least one abnormal chest findings of diminished breath sounds,

rhonchi, crackles or wheezes.

UPDATE HIGHLIGHTS

1. A patient presenting with a history of cough and/or respiratory difficulty

should be evaluated for the possible presence of pneumonia. However, the lack of

cough does not necessarily imply the absence of the disease as it may not be

present as an initial presentation in 24% of cases with radiographic pneumonia.

This is particularly true in the younger age group.

2. There are physical signs that are useful to predict the presence of pneumonia

using chest x ray as reference standard.

In four studies involving children below 5 years old, age-specific tachypnea

as defined by the World Health Organization [WHO] remains to be the best single

predictor. Another useful single physical sign is the presence of chest indrawing.

A combination of tachypnea and chest indrawing provides a higher probability as

to the presence of pneumonia. In one study, the combination of tachypnea, low

oxygen saturation on admission and nasal flaring gave the highest predictive

value among all other signs and symptoms.

In two studies dealing with patients older than 5 years, tachypnea alone, or

in combination with fever and crackles are reliable predictors.

3. The absence of either age-specific tachypnea as defined by WHO or chest

indrawing does not rule out the presence of pneumonia.

9

Annotation 1A. Background.

1. The Task Force on pCAP adopted the recommendation as provided by the

International Union Against Tuberculosis and Lung Disease that pneumonia should be

one of the considerations in a child with acute illness presenting with either cough or

difficulty of breathing [Enarson P, 2004]. However, it is important to note that cough may

not be necessarily present, as it was noted to be absent as an initial presentation in 24% of

radiologic pneumonia [Taina Juve´n, 2003]. This phenomenom has been observed to be

most common in the younger age group.

2. Basis for establishing clinical predictors

a. For the purpose of searching relevant literature in determining the clinical

predictors for pneumonia, the Task Force on pCAP has agreed to consider

radiographic findings as the benchmark in defining the presence or absence of

childhood pneumonia.

b. Acknowledging inter-observer variability in analyzing chest x-ray studies

[Swingler GH, 2001], the World Health Organization has standardized the

radiographic interpretation of a child with pneumonia [World Health Organization

Pneumonia Vaccine Trial Investigators’ Group, 2001]. Using this standard, the variability

has considerably improved, with a kappa index for the presence of alveolar

consolidation at > 0.60 [Cherian T, 2005], and 0.70 (95% CI 0.56–0.83)

[Castro AV, 2006].

Annotation 1B. Clinical presentation predictive of radiographic pneumonia

a. There is one [1] study dealing with identifying patients with radiographic

pneumonia in the out-patient department

• Among 1932 patients aged 2-59 months, cough and tachypnea,

and difficulty of breathing and tachypnea had a relative risk [RR] of 1.18

(95% CI 0.41-3.43) and 0.80 (95% CI 0.56-1.13), respectively.

[Hazir T, 2006].

b. There is one [1] study dealing with identifying patients with radiographic

pneumonia in the combined out-patient department and emergency room

• Among 181 patients aged 3 months to 5 years, cough of 5 days duration

with tachypnea has a + LR [or positive likelihood ratio] of 2.4 (95% CI

1.5-3.8) and –LR [or negative likelihood ratio] of 0.27 (95% CI 0.19-

0.39); chest indrawing +LR of 8.7 (95% CI 1.3-62.4) and –LR of 0.77

(95% CI 0.70-0.85); fever +LR of 1.3(95% CI 1.1-1.7) and –LR of 0.26

(95% CI 0.13-0.51); crackles +LR of 3.1 (95% CI 1.8-5.3) and –LR of

10

0.15 (95% CI 0.09-0.25); and combination of tachypnea and chest

indrawing +LR of 9.1 (95% CI 1.2-64.1) and –LR of 0.76 (95% CI 0.69-

0.84) * [de la Cruz R, 2007].

c. There are five [5] studies dealing with identifying patients with radiographic

pneumonia in the Emergency Room

• Among 207 patients aged 5-12 years old, the combination of

cough < 2 weeks duration, fever lasting less than 7 days,

RR>30 breaths/minute and crackles has a +LR of 4.95 and –LR of 0.36

[Ocbina P, 2006].

• Among 165 children aged 6-59 months, a history of previous respiratory

distress and persistence of tachypnea after bronchodilator challenge test

has a +LR of 1.84 and a –LR of 0.6 [Castro AV, 2005].

• Among 510 patients aged 2-59 months of age with cough and with any

one of the following [Mahabee-Gittens EM, 2005 ]:

§ RR greater than 60 per minute across all ages has

+LR of 2.6 (CI 95% 1.6-4.3), and -LR of 0.77

§ Age > 12 months has +LR of 1.5 (CI 95% 1.2-1.9),

and –LR of 0.59

§ Nasal flaring ( among patients aged > 12 months)

+LR of 5.2 (CI 95% 2.2-12.2), and –LR of 0.71

§ Combination of RR ≥50/min, O2 Sat ≤96% and nasal

flaring has + LR of 11.0 (CI 95% 2.4-49.8)

• Among 570 patients aged 1-16 years of age, tachypnea has +LR of 2.6

and -LR of 0.90; and combination of fever, decreased breath sounds,

crackles and tachypnea has +LR of 1.04 and –LR of 0.20 [Lynch T, 2004 ].

• Among 76 patients from birth to 6 mo of age [de Fatima M, 2005],

§ RR greater than 50 with bacterial etiology has a +LR of 1.2

and a -LR of 0.63;

and with a viral etiology +LR of 1.2 and -LR of 0.37

§ Chest indrawing with bacterial etiology has a +LR 2.3

and a -LR of 0 .70;

and with viral etiology +LR of 1.7 and -LR of 0.67

___________________________________________ *Likelihood ratio [LR] of around 1 indicate that no useful information for ruling the diagnosis in or out has

been produced from the clinical findings. A LR that is further away from 1 increases reliability. A high

likelihood ratio (e.g. LR>10) indicate that the sign or symptom [or any diagnostic test] can be used to rule

in the disease, while a low likelihood ratios (e.g. LR<0.1) can rule out the disease. Please see Appendix B.

11

CQ 2. Who will require admission?


1. A patient who is at moderate to high risk to develop pneumonia-related

mortality should be admitted [Grade D].

2. A patient at minimal to low risk can be managed on an outpatient basis [Grade D].

UPDATE HIGHLIGHTS

1. Single evidence supports the current recommendation on risk classification scheme.

2. A single clinical index that suggests the need for admission because of possible

hypoxemia is chest indrawing.

3. Indices that predict mortality include young age, malnutrition, lack of Hib/measles

vaccination, and high oxygen requirement on admission.

Annotation 2A. Risk classification scheme

Among 221 patients with an impression of pCAP, none of the 61 and 80 patients

classified as pCAP A and B respectively were admitted within 48 hours. Similarly, none

of the 84 patients admitted as pCAP C were discharged or admitted to ICU within 48

hours after admission [Pocsidio C, 2007]. See Appendix C for the table showing the risk

classification.

Annotation 2B. Individual indices predicting the need for admission

1. Physical examination of the chest in predicting hypoxemia

Among 150 patients aged 2-60 months, chest indrawing has a +LR of 5.7

and -LR of 0.39 in predicting the presence and absence respectively of hypoxemia

[Basnet S, 2006].

2. Age and nutrition in predicting mortality

Among 30 mortalities because of pneumonia, young age [2-5 months] and weight

for age z-score less than -2 SD have an OR of 2.20 (95% CI 1.06-4.54) and

1.86 (95% CI 0.89-3.87), respectively [Lupisan SP, 2007].

3. Hib/measles vaccination on admission in predicting mortality

Among 102 mortalities because of pneumonia, the absence of measles/HIb

vaccination has an OR of 15.89 (95% CI 3.473-72.784), and

8.31(95% CI 3.5-19.3), respectively [Sadang-Saguinsin S, 2006].

Annotation 2C. Day care management of pCAP C

Among 251 patients aged 2-59 months with severe and very severe pneumonia without

any associated co-morbidities, successful management was possible in a day care setting

among 93.2% (95% CI, 89-96) of patients [Ashraf H, 2007].

12

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?


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 [Grade D].

UPDATE HIGHLIGHT

The low risk of bacteremia does not warrant blood culture determination in

nonsevere pneumonia.

Annotation 3A. Indication for radiographic and laboratory tests

The Task Force on pCAP has not encountered studies investigating the value of WBC,

differential count, CRP and ESR in the diagnosis of pCAP patients being managed on an

outpatient basis.

Annotation 3B. Blood culture

In 540 patients aged 2-24 months, the risk of bacteremia among patients seen as

outpatient is 1.6%. (95% CI 0.7-2.9). Streptococcocus pneumoniae was the causative

organism in all cases [Shah S 2003].

Annotation 3C. Predictor for bacterial pathogen

Serum procalcitonin has been used to differentiate between viral, atypical and bacterial

pathogen in 100 patients aged less than 2 years to more than 5 years [74 outpatients and

26 inpatients]. A cut-off limit of > 2.0 ng/ml has a +LR of 1.69 and -LR of 0.73 for

Streptococcus pneumoniae, and a +LR of 2.31 and –LR of 0.54 for Mycoplasma sp and

Chlamydia sp, respectively [Don M 2007]. This test is not currently available locally.

13

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?


1.The following should be routinely requested:

a. Chest x-ray PA-lateral [Grade B]

b. White blood cell count [Grade C]

c. Culture and sensitivity of

Blood for PCAP D [Grade D]

Pleural fluid [Grade D]

Tracheal aspirate upon initial intubation [Grade D]

Blood gas and/or pulse oximetry [Grade D]

2.The following may be requested:

Culture and sensitivity of sputum for older children [Grade D]

3. The following should not be routinely requested:

a. Erythrocyte sedimentation rate [Grade A]

b. C-reactive protein [Grade A]

UPDATE HIGHLIGHTS

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 and CRP have 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.

14

Annotation 4A. Chest x-ray

Radiographic examination offers the following information.

1. Chest x-ray has been used as a tool to predict the type of pathogen

Chest x-ray is an integral part of the clinical prediction rule

[see Clinical Question 5 and Appendix D] in initiating antibiotic

therapy [Moreno L, 2006]. However, its value as an individual tool in

differentiating bacterial from other types of infection is

insignificant as shown in one report [Michelow IC, 2004]. In this

study of 154 patients aged 2 months–17 years, the presence of

lobar or segmental consolidation with or without effusion can be

seen among different pathogens such as bacterial, viral and

atypical organisms (p value = 0.06).

A compounding variable is the presence of mixed causative agents

in about a third of cases of pneumonia in which the radiographic

pattern has been shown to be similar to that seen in single pathogen

[Tsolia MN, 2004; Taina Juve´ n, 2004; Michelow IC, 2003; Don M, 2005;

Tajima T,2006; Lehtinen P,2006; Huang HH,2006; Chiang WC,2007].

2. Chest x ray has been used as an individual tool to assess severity of

pneumonia

Presence of necrotizing pneumonia and/or empyema

Among 131 patients aged <18 years, the presence of

necrotizing pneumonia and/or empyema was significantly

more likely to be present in multilobar (≥2 lobes)

involvement (OR 2.83, 95% CI 1.27-6.33) [Lin J,2006].

3. Chest x ray has been used as an individual tool to predict subsequent

course

a. Predictor of prolonged fever and hospitalization, and pleural

effusion

Among 167 patients > 12 months of age, left-sided

pneumonia was significantly associated with prolonged

fever (p=0.02) and hospitalization (p=0.043), and the

presence of pleural effusion (OR 2.65; 95% CI 1.09–6.47;

p value=0.031) compared with right-sided pneumonia

[Grafakou O,2004].

15

b. Predictor of mortality

Among 102 mortalities because of pneumonia, multilobar

(≥2 lobes) involvement has an OR of 2.55 (95% CI 1.56.-

5.64) of mortality [Sadang-Saguinsin S, 2006].

In 30 mortalities because of pneumonia, the presence of

dense infiltrates has an OR of 3.89 (95% CI 1.75-8.67)

[Lupisan SP, 2007].

c. Predictor of treatment failure

Among 20% of 218 patients, bilateral consolidation has an

OR of 3.10 of having treatment failure on the 72nd

hour of

admission [Victor R, 2007].

Annotation 4B. WBC

Evidence is weak in using white blood count as an individual tool to predict bacterial

pathogen

a. Among 132 patients <11 months to >5 y old, the +LR and - LR for

WBC>13,000 x 109/L are 1.29 and 0.73, and WBC>17,000 x 10

9/L are

1.89 and 0.80, respectively [Korppi M, 2004].

b. Among 862 patients with proven RSV infection aged 6–2398 days,

WBC > 15,000 x 109/L, the probability of a concurrent serious bacterial

infection is 4.7% [Purcell K, 2007].

c. Among 154 patients aged 2 months – 17 years, no statistical

significance exists among WBCs of bacterial, viral, atypical organisms

and mixed infection (p value = 0.76) [Michelow IC, 2004].

Annotation 4C. Acute phase reactants

1. C reactive protein [CRP]

• Evidence is inconclusive in using CRP to predict the presence of bacterial

pathogen

a. Among 132 patients aged <11 months to >5 years old,

CRP > 146 mg/dl has a +LR of 1.75 and -LR of 0.43.

[Korppi M, 2004].

16

b. Among paired serum samples from 265 patients,

CRP from 6 to 250 mg/L using latex agglutination test has

sensitivity of 100% and specificity of 87% [Requejo H, 2003].

• In one study, a CRP level ≥ 12 mg/dl has an OR of 3.51 (95% CI 1.71-

7.66) to predict the presence of necrotizing pneumonia and/or empyema

[Lin K, 2006].

2. Erythrocyte sedimentation rate [ESR]

In one study, there is evidence that ESR can be used to predict the

presence of a bacterial pathogen. Among 132 patients aged <11 months

to >5 y old, ESR at a value of 63 mm/h has a +LR of 3.50 and -LR 0.84

[Korppi M,2004].

3. Serum procalcitonin

In two studies, there is evidence that serum procalcitonin may predict the

presence of a bacterial pathogen. This test however is not currently

available locally

a. Among 132 patients aged <11 months to >5 y old, a

procalcitonin level of > 0.84 ng/L has a +LR of 2.05 and a -LR

0.76 [Korppi M, 2004].

b. Among 57 patients less than 15 years old with Streptococcus

pneumoniae, procalcitonin > 1 ng/L found in only 14 patients had

+LR of 2.40 [Korppi M,2003].

Annotation 4D. Microbiology

1. There are no studies dealing with determining the impact of having to obtain

microbiologic examination on the overall outcome of pCAP.

2. Two studies have shown the yield for blood culture as follows:

a. 1.2% among 157 patients [Tajima T, 2006].

b. 6.2% among 75 patients [M. N. Tsolia, 2004].

3. Immunological assay and PCR

a. Among 550 paired samples for Streptococcus pneumoniae and

Haemophilus influenzae type b polysaccharide antigen, CIE, LA and Dot-

ELISA using serum samples had a sensitivity of 91.1% to 100%, and a

specificity of 56.4% to 100% [Requejo HI, 2007].

17

b. Among 107 patients, latex particle agglutination test [LPAT] performed

in urine samples to detect Streptococcus pneumoniae and Haemophilus

influenzae type b polysaccharide antigen, has a +LR of 7.7 and -LR of

0.25 [Nunes A, 2004].

c. Among 389 patients, the sensitivity and specificity using pathogen-

specific molecular beacon probes were as follows: 96.2% and 93.2% for

Streptococcus pneumoniae, 95.8% and 95.4% for Hemophilus influenzae,

100% and 100% for Streptococcus pyogenes, and 100% and 95.4% for

Mycoplasma pneumoniae, respectively [Morozumi M,2006].

Annotation 4E. Oxygen saturation and/or blood gas

In addition to the use of determining oxygen saturation and/or blood gas to titrate Fi02 in

maintaining adequate oxygenation, it can also be utilized to predict mortality. Among

102 children aged 3 months to 19 years, a high oxygen requirement on admission has an

OR of 8.31 (95% CI 3.5-19.3) at risk for mortality [Sadang-Saguinsin S, 2006].

18

CQ 5. When is antibiotic recommended?


An antibiotic is recommended

1. for a patient classified as either PCAP A or B and is

a. beyond 2 years of age [Grade B]; or

b. having high grade fever without wheeze [Grade D]

2. for a patient classified as PCAP C and is

a. beyond 2 years of age [Grade B]; or

b. having high grade fever without wheeze [Grade D]; or

c. having alveolar consolidation in the chest x-ray [Grade B]; or

d. having white blood cell count >15,000 [Grade C]

3. for a patient classified as PCAP D [Grade D]

UPDATE HIGHLIGHTS

1. Epidemiology

a. Recent epidemiologic trend shows that more than 50% of hospitalized

cases of pCAP will require antibiotic.

b. 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.

a. 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.

b. Other individual parameters include the following.

• Increasing age generally correlates with the presence of

antibiotic-requiring pathogen. Identifying a specific age as to

when an antibiotic should be started is difficult.

• There is single evidence in the use of ESR with a value of 63

mm/h in predicting the presence of a bacterial pathogen.

• There is weak evidence in the use of clinical symptomatology,

chest x-ray, WBC and CRP as predictors of bacterial pathogen.

19

Annotation 5A. Establishing the etiology

A. Microbiology

There are five [5] studies that have looked simultaneously into viral, bacterial,

atypical organisms and mixed infection [Michelow I, 2004,; Don M, 2005; Tsolia MN,

2005; Tajima T, 2006; Chang WC, 2007]. Etiology was determined through different

methodologies using culture, serology, and pneumolysin-based polymerase chain

reaction assays. It is important to note that all patients in these studies are

hospitalized [except in one study dealing with both ambulatory and hospitalized

patients], and are from developed economies where the rate of vaccination is

higher than in the third world. As the table below indicates, organisms requiring

antibiotic coverage accounts for more than 50% across all ages. The importance

of mixed infection needs to be further studied as there is an observational

evidence of a high morbidity from 2% to 35%.

Author

Year

Age

[Years]

Subjects

N

Known

Etiology

N [%]

Virusa

%

Bacteriaa

%

Atypical

Pathogena

%

Mixed

Infection

%

Chiang

2007

0.1-16

1702

646 [37.9%]

5.5%

10.3%

20.3%

2.0%

Tajima

2006

0.1-13

157

126 [80.2%]

44.0%

80.1%

25.3%

18.0% b

Don

2005

0.3-16

101

66 [65.3%]

42.0%

30.3%

53.0%

30.0%

Tsolia

2005

5-14

75

58 [77.3%]

65.0%

7.0%

48.2%

35.0%

Michelow

2004

0.2-17

154

122 [79.2%]

45.0%

60.0%

33.6%

23.0%

MEAN

23.6%

26.5%

26.0%

10.7%

TOTAL

2189 1018 [46.5%]

a All cases including mixed infection

b 28 (17.8%) had viral bacterial infection. 1 (0.6%) had Mycoplasmal-bacterial pneumonia

20

B. Establishing the etiology

The Task Force on pCAP recognizes the importance of establishing the presence

of a bacterial pathogen through culture studies. However, there are limitations to

this approach such as invasiveness of the procedure as in lung puncture, low yield

(1.2% to 26% in blood culture) [Michelow I, 2004; Tsolia MN, 2005; Tajima T, 2006],

and the availability of results at a later time.

There are tests that can be used to rapidly detect bacterial pathogens but which are

either not readily available locally or expensive. These are immunological assays

(CIE, LA and Dot-ELISA in detecting Streptococcus pneumoniae and

Haemophilus influenza b antigen with sensitivity of 91.1% to 100% and

specificity of 49.5% to100% in 550 paired serum, pleural fluid and urine samples)

[Requejo HI, 2007]; PCR (pathogen-specific molecular beacon probes) with the

following sensitivity and specificity in 389 patients: 96.2% and 93.2% for

Streptococcus pneumoniae, 95.8% and 95.4% for Haemophilus influenzae, 100%

and 100% for Streptococcus pyogenes, and 100% and 95.4% for Mycoplasma

pneumoniae [Morozumi M, 2006]; and latex particle agglutination test [sensitivity of

77.3% (95% CI, 61.8 - to 88.0) and specificity of 90.3% (95% CI, 79.5 - 96.0) in

detecting Streptococcus pneumoniae and Haemophilus influenzae type b

polysaccharide antigen in urine samples of 107 patients [Nunes A, 2004].

Annotation 5B. Surrogate predictors of bacterial etiology

A. Clinical prediction rule

A clinical prediction rule among hospitalized children aged one month to five

years has been developed to determine the presence of a bacterial pathogen. An

aggregate bacterial pneumonia score [BPS] of > 4 has a sensitivity and specificity

of 100% (95% CI 84.6–100) and 93.9% (95% CI 87.8–97.5) respectively. The

computed +LR and –LR are > 10 and <0.1 respectively. See Appendix D for BPS

[Moreno L, 2006]. A limitation of this study is the failure to include mixed causative

agents and Mycoplasma infection among its subjects.

21

B. Individual clinical predictors

1. Age

a. A summary of four [4] epidemiologic reports on all types of organisms

that stratifies the occurrence of etiologic agents as to age is shown below.

Extracted data are heterogenous making it difficult to come up with a

strong conclusion as to what age should antibiotic be likely started.

[Michelow I, 2004 ;Don M, 2005; Tajima T 2006;Chang WC 200]. In two studies,

increasing age correlates with a higher chance of the presence of bacterial

agents. In all four studies, there is a trend in increasing frequency of

atypical organism.

Author

Year

Age

[Years] Subjects

[N] Known

Etiology

[N]

Virus a

[%]

Bacteria a

[%]

Atypical

Pathogena

[%]

Mixed

Infection

[%]

Chiang

2007

0.1-16

< 2

2-5

> 5

1702 653 5.5

6.6

6.9

0.9

10.3

5.2

13.2

8.5

20.3

5.0

16.5

31.0

2.0

Tajima

2006

0.1-13

< 2

2-5

> 5

157

126 40.0

52.7

47.3

0

43.0

69.6

32.8

4.2

18.0

3.5

42.8

64.2

19.0; [2.0b]

83.0

17.0

0

Don

2005

0.3-16

< 2

2-5

> 5

101 66 18.8a

31.6

57.8

10.5

17.5

22.2

38.8

38.8

34.6

5.7

22.8

71.4

29.7

36.8

22.7

34.2

Michelow

2004

0.2-17

< 2

2-5

> 5

154 122

19.0

55.0c

48.0c

38.0c

26.0

55.0c

68.0c

55.0c

11.0

47.0 d

53.0

23.0

aSingle and mixed infection

bBacterial and Mycoplasma sp

cInterpolated data

dPercentage data applicable to children below 5 years

22

b. There are five [5] pathogen-directed, across-all-ages studies dealing with

atypical organisms [Othman N, 2005; Garcia MC, 2002-2005; Tsai MH,2005; Butun Y,2006;

Bamba M, 2006]. Two studies, one of which was done in the local setting,

were from developing economies. As shown below, more than half of the total

number of cases with atypical organism are children below 5 years of age in three

of the five studies.

Author

Year

Age

[Years]

N

Age with

+ antibody titer for

Mycoplasma sp and/or

Chlamydia sp

[Years]

Prevalence

[%]

Butun

2006

0.3-12 100 <5 53.0

Bamba

2006

<4-13 141 <4

20.0

Othman

2005

0.5-15 76 <5 36.8

Garcia

2005

1-10 142 <5 63.4

Tsai

2004

1-14 26 <5 53.8

2. Clinical symptomatology

Among 254 inpatients [mean age of 3.8 years] with radiographic

pneumonia and proven etiology, the presence of decreased breath sounds

is the only single clinical sign noted among patients with bacterial

pathogen as compared with viral infection (p<0.05) [Juve’n T, 2003].

C. Individual ancillary parameters predicting bacterial pathogen

1. Erythrocyte sedimentation rate [ESR]

Among 132 patients aged <11 months to >5 years old, ESR of 63 mm/h

has a +LR of 3.50 and a -LR of 0.84 [Korppi, 2004].

23

2. White blood cell count [WBC]

a. Among 132 patients <11 months to >5 years old, WBC cut-off

levels of > 13,000 x 109/L, and > 17,000 x 10

9/L have +LR of 1.29 and

-LR of 0.73, and +LR of 1.89 and -LR of 0.80, respectively [Korppi,2004].

b. Among 862 patients with proven RSV infection aged 6 days–8 years

and a WBC cut-off level of > 15,000 x 109/L, the probability of a

concurrent serious bacterial infection is 4.7% [Purcell K,2007].

c. Among 154 patients aged 2 months – 17 years, no statistical difference

exists as to the WBC levels among bacterial, viral, atypical and mixed

infection (p value = 0.76) [Michelow IC, 2004].

3. C-reactive protein [CRP]

a. Among 132 patients aged <11 months to >5 years old, a CRP value

of > 146 mg/dl has a +LR of 1.75 and a -LR of 0.43[Korppi, 2004].

b. Among paired serum samples from 265 patients, qualitative

determination of CRP has a sensitivity of 100% and specificity of 87.3%

in detecting Streptococcus pneumoniae, Haemophilus influenzae b,

Staphylococcus aureus and Neisseria meningitidis [Requejo H,2003].

4. Chest x-ray studies a. Among 54 patients aged 2 months to 17 years, no statistical difference

exists as to the presence of lobar or segmental consolidation with or

without effusion among bacterial, viral, atypical organisms and mixed

infection (p value = .06) [Michelow IC, 2004].

24

CQ 6. What empiric treatment should be administered if a bacterial etiology is

strongly considered?


1. For a patient classified as PCAP A or B without previous antibiotic, oral

amoxicillin [40-50 mg/kg/day in 3 divided doses] is the drug of choice [Grade D].

2. For a patient classified as PCAP C without previous antibiotic and who has

completed the primary immunization against Haemophilus influenza type b,

penicillin G [100,000 units/kg/day in 4 divided doses] is the drug of choice [Grade D].

If a primary immunization against Hib has not been completed, intravenous

ampicillin [100 mg/kg/day in 4 divided doses] should be given [Grade D].

3. For a patient classified as PCAP D, a specialist should be consulted [Grade D].

UPDATE HIGHLIGHTS

1 Epidemiology

a. 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.

b. 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 infection, and for ampicillin with Haemophilus

influenzae.

3. Empiric antibiotic therapy

a. For pCAP A and B [nonsevere pneumonia], there is evidence for the use

of amoxicillin [45 mg/kg/day in three divided doses for a minimum

duration of three 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.

b. 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,

parenteral ampicillin is the best choice considering its cost.

25

Annotation 6A. Causes of pCAP requiring antibiotic coverage

A. Predominant pathogen

Among patients with known etiology, Streptococcus pneumoniae and atypical

organisms generally account for majority of causes of pCAP across all ages

[Chang WC, 2007; Huang HH, 2006; Tajima T, 2006; Don M, 2005; Tsolia MN, 2005; Michelow I, 2004]

aStreptococcus pneumoniae is more common above 5 years of age[Chiang, 2007; Michelow 2004].

B. Emerging pathogen: Community-acquired methicillin-resistant Staphylococcus aureus

[CA-MRSA]

The epidemiology of community-acquired methicillin-resistant Staphylococcus

aureus [CA-MRSA] has been recently reviewed. In one study conducted in

Driscoll Children’s Hospital, Corpus Christi Texas USA, 93% of a total of 1002

MRSA were identified from 1990 through 2003 as CA-MRSA. Cases ranged

from none to nine per year from 1990 through 1999 and then increased

exponentially from 36 in 2000 to 459 in 2003 [Purcell K. 2005; Paintsil E,2007]. In the

local setting, the Antimicrobial Resistance Surveillance Program reported a

hospital rate of MRSA of 31% in 2005 and in 2006

[Carlos CC,2005; Carlos CC,2006].

Author

Year

Age

[Years] Streptococcus

pneumoniaea

[%]

Haemophilus

influenazae [%]

Mycoplasma

sp

[%]

Chlamydia

sp [%]

Chiang

2007

0.1-16

17.4% 0.4% 28.6% 0%

Tajima

2006

0.1-13

35.7%

26.1% 17.4% 0%

Huang

2006

2.0-14

8.9%

1.2%

7.1%

1.8%

Don

2005

0.3-16

17.8%

4.5%

26.7%

7.9%

Tsolia

2005

5.0-14 7.0% 0% 35.0% 3.0%

Michelow

2004

0.2-17

73.0% 0% 14.0% 9.0%

26

Annotation 6B. Antibiotic resistance

A. Antibiotic resistance surveillance reports

1. Local data : Antimicrobial Resistance Surveillance Program

Of 24 112, 23 749, 29 782 and 25 768 isolates for 2003, 2004, 2005 and 2006

respectively as reported by the Research Institute of Tropical Medicine, the

resistance rates of hospital infection involving Streptococcus pneumoniae and

Hemophilus influenzae to different antibiotics are shown below [Carlos CC,2003;

Carlos CC, 2004; Carlos CC,2005; Carlos CC,2006]:

a Screening with 1 ug oxacillin disc

2. Asian data: Asian Network for Surveillance of Resistant Pathogens

Of 555 isolates of Streptococcus pneumoniae from ten Asian countries (Korea,

China, Hong Kong, Thailand, Taiwan, India, Sri Lanka, Singapore, Malaysia and

Vietnam) as reported by the Asian Network for Surveillance of Resistant

Pathogens (ANSORP), 329 (59.3%) were resistant to erythromycin

[Jae-Hoon Song, 2004].

3. Individual country data : Japan

Among 2,462 clinical specimens collected between April 2002 and March 2004

from pediatric outpatients with respiratory tract infections, about 10 macrolide-

resistant Mycoplasma pneumoniae (MICs of >1ug/m) out of a total of 195

isolated strains have been reported. Resistance rate in this study is 1.9%

[Morozumi M,2005].

.

Penicillin a

Chloramphenicol

Cotrimoxazole

Ampicillin

2003

04

05

06

2003

04

05

06

2003

04

05

06

2003

04

05

06

Streptococcus

Pneumoniae

9%

5%

11%

6%

3%

5%

4%

5%

9%

15%

16%

14% No

data

No

data

No

data

No

data

Haemophilus

Influenzae

No

data

No

data

No

data

No

data

13%

10%

20%

14%

18%

36%

15%

16%

13%

10%

10%

9%

27

Annotation 6C. Antibiotic regimen for PCAP A or B [non severe pneumonia]

A. Oral Amoxicillin

1. Comparative trial

a. In a Cochrane systematic review using failure rate as an outcome

measure, the rate was higher in cotrimoxazole compared to amoxicillin

(OR 1.33; 95% CI 1.05 - 1.67) [Kabra SK;2006].

b. In a Cochrane systematic review using failure rate as an outcome

measure, the rate was lower in the amoxicillin group compared to

chloramphenicol (OR 0.64; 95% CI 0.41 - 1.00) [Kabra SK;2006].

c. There are two [2] studies comparing amoxicillin with either

azithromycin or erythromycin.

• Amoxicillin versus azithromycin using end-of-treatment chest

x-ray and clinical parameters as outcome measures

Among 47 patients aged 1 month - 14 years, using chest x-

ray on day 7 as outcome measure showed improvement

greater than 75% compared with baseline in the

azithromycin group versus those who received amoxicillin

[81.0% vs. 60.9%, p value = 0.09]. No difference exists

between the two groups in other parameters such as fever,

crackles and use of accessory muscles on day 7 and 14 of

treatment [Kogan R;2003].

• Amoxicillin versus erythromycin using cure rate as outcome

measure

Among 85 patients aged 4 months-19 years, there was no

difference between amoxicillin and erythromycin as to cure

rate (p value = 0.274) [Romulo AC, 2006].

d. For those with known hypersensivity to amoxicillin, a macrolide

antibiotic can be considered.

28

2. Treatment regimen

a. Standard dose versus double dose using treatment failure as

outcome measure

Among 876 patients aged 2-59 months, the standard dose of

amoxicillin at 45 mg/kg/day did not show any statistically

significant difference compared with double dose amoxicillin at 90

mg/kg/day using treatment failure by day 5 (4.5% in the standard

and 5.7% in the double dose, p value = 0.55), and cumulative

treatment failure including relapses (5.9% in the standard and 7.9%

in the double dose, p value=0.29) as outcome measures

[Hazir T,2007].

b. TID dosing frequency versus BID using pharmacokinetic studies as

outcome measure

Among 266 patients aged 3-59 months in whom amoxicillin was

given orally either at 25 mg/kg/dose BID or 15 mg/kg/dose TID,

all but two children had plasma amoxicillin concentrations above

0.5 ug/ml for >50% of the dose interval [Fonseca W, 2003]. There are

no studies comparing the clinical outcome of patients with

pneumonia on TID regimen versus BID.

c. Three-day versus five-day duration using clinical cure rate and relapse

rate as outcome measures

Among 2188 patients aged 2-59 months, clinical cure rates with

three days and five days treatment were 89.5% and 89.9%,

respectively (absolute difference 0.4, 95% CI 2.1-3.0). There was

no difference in relapse rate between the two groups after 5 days

(RR = 1.22; absolute difference 1.0, 95% CI 1-3). Limitations such

as the study was performed in patients with clinical suspicion of

pneumonia without radiographic evidence and insufficient

detailing of patients history were noted [Agarwal, 2004].

29

B. Other antibiotic options

1. Cotrimoxazole

a. Comparative trial using cure rate as outcome measure

There is one Cochrane systematic review dealing with antibiotic treatment

of pCAP showing procaine penicillin having better cure rate compared

with co-trimoxazole (OR 2.64; 95% CI 1.57 - 4.45) [Kabra SK;2006].

b. Treatment regimen using treatment failure rate as an outcome measure

Among 1134 patients aged 2-59 months, treatment failure occurred in

112 (19.4%) on standard dose [4 mg trimethoprim plus 20 mg

sulfamethoxazole/kg of body weight] group and in 118 (21.2%) on

double-dose (RR 1.10; 95% CI 0.87–1.37) [Zeba A,2005].

2. Azithromycin, erythromycin and co-amoxyclavulanic acid using cure rate as an

outcome measure

In a Cochrane systematic review dealing with antibiotic treatment of

pCAP, there was no difference between azithromycin and erythromycin

(OR 1.17; 95% CI 0.70 - 1.95); or azithromycin and co-amoxyclavulanic

acid (OR 1.02; 95% CI 0.54 - 1.95) [Kabra SK;2006].

3. Clarithromycin extended release using cure rate as an outcome measure

Among 21 patients aged 6 to 16 years, there is no difference as to cure rate

between extended release clarithromycin once a day and the standard

clarithromycin twice a day (90% vs 90.1%) [Block SL,2006].

4. Antibiotics for community acquired lower respiratory tract infections (LRTI)

secondary to Mycoplasma pneumoniae [Gavranich JB,2005].

A Cochrane systematic review dealing with antibiotics for community

acquired lower respiratory tract infections (LRTI) failed to find any

randomised controlled trial which specifically looked at the effectiveness

of antibiotics for LRTI secondary to M. pneumoniae. In the subgroup of

children with LRTI secondary toM. pneumoniae the intervention was a

macrolide antibiotic versus a non-macrolide antibiotic, usually

amoxicillin-clavulanate. This subgroup identified only 38 children with M.

pneumoniae infection and there were insufficient data to analyse the

efficacy of macrolide antibiotics in this group.

30

ANNOTATION 6D. PCAP C or severe pneumonia

A. Monotherapy

Parenteral penicillin vs oral amoxicillin

• A Cochrane systematic review using failure rate as an outcome

measure showed no difference between injectable penicillin and oral

amoxicillin (OR 1.03; 95% CI 0.81 to 1.31) [Kabra SK;2006]. Included in

this review is a study among 1702 patients aged 3-59 months who

received either oral amoxicillin or parenteral penicillin. Results showed

that treatment failure was 19% in either group (risk difference –0.4%,

95% CI -4.2 - 3.3) [Addo-Yobo, 2004].

• Among 246 patients aged 6 months to 16 years with radiologically

confirmed pneumonia, no significant difference exists between the group

on oral amoxicillin versus IV benzylpenicillin using time for

temperature to settle <38C for 24 continuous hours (p value = 0.001) as

the outcome measure. Using another outcome measure, the median time

to complete resolution of symptoms was 9 days in both groups

[Atkinson M, 2007].

B. Combination therapy

1. Parenteral penicillin plus chloramphenicol versus ampicillin using cure rate

and duration of hospitalization as outcome measures

In a Cochrane systematic review, the cure rates (OR 0.48; 95% CI 0.15 to

1.51), and duration of hospitalization were similar in the two groups

(weighted mean difference (WMD) 0.1; 95% CI -1.13 to 0.93)

[Kabra SK; 2006].

2. Parenteral penicillin plus chloramphenicol versus ceftriaxone using cure rate as

outcome measure

In a Cochrane systematic review using cure rate as outcome measure, the

use of parenteral penicillin plus chloramphenicol was as efficacious

compared with ceftriaxone alone (OR 1.36; 95% CI 0.47 to 3.93)

[Kabra SK; 2006].

31

3. Parenteral penicillin plus chloramphenicol versus cefuroxime using clinical

parameters as outcome measures

Using clinical parameters as outcome measures among 88 patients aged

2 months-18 years, early defervescence (p value=0.006), absence of

tachypnea (p value=0.024), absence of chest retractions (p value=0.001),

and shorter hospital stay (p value=0.029) were noted among patients

treated with penicillin G/Chloramphenicol compared with cefuroxime

[Carlos GP,2006].

4. Parenteral penicillin plus gentamicin versus chloramphenicol using

re-hospitalization rate, death rates and adverse events as outcome measures

In a Cochrane systematic review using re-hospitalization rate before 30

days as outcome measure, the use of parenteral penicillin plus gentamycin

was better than chloramphenicol alone (OR 1.61; 95% CI 1.02 to 2.55).

Death rates and adverse events were similar in both groups [Kabra SK;2006].

5. Parenteral penicillin plus gentamicin versus amoxicillin/clavulanate using

clinical parameters as outcome measures

Using clinical parameters as outcome measures among 71 patients aged

2-59 months, the mean time taken for normalization of tachypnea,

hypoxia, chest wall indrawing and inability to feed was similar for both

groups receiving penicillin plus gentamicin versus amoxicillin/clavulanate

(p value > 0.05) [Bansal A,2006]

6. Parenteral ampicillin plus gentamicin versus parenteral ampicillin alone using

clinical parameters as outcome measures

Using clinical parameters as outcome parameters among 40 patients aged

2 months to 5 years who received either combination therapy of IV

ampicillin and gentamicin versus IV ampicillin alone, fever clearance

time, improvement of respiratory rate, improvement of chest indrawing

and resolution of rhonchi were comparable between the two groups

(p value <0.05) [Hasali A 2005].

32

7. Other treatment regimens

a. Amoxicillin/sulbactam versus cefuroxime using defervescence as

outcome measure

Using defervesecence as an outcome measure among 62

patients aged 3 months-15 years who received either

amoxicillin/sulbactam or cefuroxime, both treatment arms

were comparable (97% for amoxicillin/sulbactam vs 100%

for cefuroxime) [Lovera D,2005].

b. Chloramphenicol

Among 250 children treated with chloramphenicol, 98%

had a favorable treatment outcome [Ayap J, 2006]

C. Community-acquired MRSA

For suspected cases of community-acquired MRSA, immediate referral to an appropriate

specialist is necessary. The following information serves to provide basic knowledge in

the therapeutic options dealing with MRSA [Strategies for Clinical Management of MRSA in the

community: Summary of an Experts’ meeting,2006; Shelburne S, 2004].

a. Antibiotic susceptibility based on culture studies should be followed.

b. Vancomycin remains to be the first line therapy for severe infections possibly

caused by MRSA.

c. Community-associated MRSA were more likely to be synergistically inhibited

by combinations of vancomycin and gentamicin (p value =0.025) versus

vancomycin alone.

33

CQ 7. What treatment should be initially given if a viral etiology is strongly

considered?


1.Ancillary treatment should only be given [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 [Grade B] or occurring as

an outbreak [Grade D].

UPDATE HIGHLIGHT

Oseltamivir remains to be the drug of choice for laboratory confirmed cases of

influenza.

Annotation 7A. Definite treatment

Influenza

• In a Cochrane systematic review, oseltamivir reduced the median duration of

illness by 26% (or 36 hours) in healthy children with laboratory-confirmed

influenza (p value < 0.001) [Matheson NJ,2007].

• In proven influenza illness among adolescents, oseltamivir reduced the incidence

of influenza-related lower respiratory tract complications resulting in antibiotic

therapy by 5.5% (4.6% vs 10.3% with placebo; p value < 0.001) [Kaiser L,2003].

• The computed number need to treat for oseltamivir is 20.

In influenza-like illness without confirmed influenza infection, no significant

difference exist between oseltamivir and placebo[Kaiser L,2003].

Annotation 7B. Ancillary treatment

Please refer to CQ 11. What ancillary treatment can be given? for recommendations

pertaining to ancillary treatment.

34

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


1. Decrease in respiratory signs [particularly tachypnea] and defervescence

within 72 hours after initiation of antibiotic are predictors of favorable

therapeutic response [Grade D].

2. Persistence of symptoms beyond 72 hours after initiation of antibiotics

requires re-evaluation [Grade B].

3. End of treatment chest x-ray [Grade B], WBC, ESR or CRP should not be

done to assess therapeutic response to antibiotic [Grade D].

UPDATE HIGHLIGHTS

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.

Annotation 8A. Treatment response

A. Background

The clinical outcome definition of ‘improved’ provided by the World Health

Organization in 1990 is a respiratory rate < age-specific range without lower chest

indrawing or danger signs (central cyanosis, inability to drink, abnormally sleepy,

and convulsions) [WHO 1990].

35

B. Response to treatment

1. Ambulatory patients

Respiratory rate

Among 876 patients aged 2-59 months with nonsevere pneumonia,

clinical improvement on the 72nd

hour is respiratory rate >5

breaths/min slower than baseline recording [Hazir T,2006].

2. Hospitalized patients

Duration of fever

Among 153 children aged 1 month to 16 years, 91% became

afebrile within 48 hours. Children with bacteremic pneumococcal

pneumonia have become afebrile within an average of 22 hours

after onset of antimicrobial therapy [Juve´ n T, 2006].

Respiratory rate

Average time of recovery from tachypnea among 71 children aged

2-59 months is 38-40 hours [Bansal A, 2006].

Oxygen saturation

Average time of recovery from SpO2 (<90%) among 71 children

aged 2-59 months is 32-33 hours [Bansal A,2006].

Chest indrawing

Average time of recovery from chest indrawing among 71 children


Inability to feed

Average time of recovery from inability to feed among 71 children


36

CQ 9. What should be done if a patient is not responding to current antibiotic

therapy?


1. If an outpatient classified as either PCAP A or PCAP B is

not responding to the current antibiotic within 72 hours,

consider any one of the following [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 [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

re-consultation with a specialist [Grade D].

UPDATE HIGHLIGHTS

1. There are no studies dealing with therapeutic interventions following

treatment failure among children having community-acquired pneumonia.

2. A definition of treatment failure for nonsevere pneumonia is as follows:

a. Same status. This is defined as respiratory rate > 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.

37

Annotation 9A. Course of action in treatment failure

There are no comparative trials specifically dealing with therapeutic interventions

following treatment failure among children having community-acquired pneumonia.

Annotation 9B. Definition of treatment failure

A. Background

The clinical outcome definitions of ‘same and worse’ status provided by the

World Health Organization in 1990 are as follows [WHO 1990] :

Same : Respiratory rate > age-specific range without lower chest

indrawing or any danger signs (central cyanosis, inability to drink,

abnormally sleepy or convulsions)

Worse : Developed lower chest indrawing or any of the danger signs

(central cyanosis, inability to drink, abnormally sleepy,

or convulsions)

B. Treatment failure

1. pCAP A and B [Nonsevere pneumonia]

Among 876 patients aged 2-59 months with nonsevere pneumonia,

treatment failure has been redefined on the 72nd

hour after initiating

antibiotic as either [a] same status : respiratory rate > age-specific range

but + 5 breaths/min to the baseline reading without lower chest indrawing

or danger signs (central cyanosis, inability to drink, abnormally sleepy or

convulsions), or [b] worse status : developed lower chest indrawing or any

of the danger signs (central cyanosis, inability to drink, abnormally sleepy

or convulsions) [Hazir T,2006].

2. pCAP C [Severe pneumonia]

There are no studies in hospitalized patients.

38

Annotation 9C. Causes of failure in the treatment of bacterial pneumonia

A. Causes of treatment failure are as follows:

1. pCAP A and B [nonsevere pneumonia]

Among 2188 patients aged 2-59 months, 10.3% were reported to be cases

of treatment failure. Causes include an association with isolation of

respiratory syncytial virus (an adjusted OR 1.95; 95% CI 1.0-3.8), and

non-adherence with treatment (OR 11.57; 95% CI 7.4-18.0)

[Agarwal, 2004].

2. pCAP C [severe pneumonia]

a. Among 71 patients aged 2-59 months, 2.8% were reported to be cases of

treatment failure. Causes include resistance to antibiotics and worsening

clinical condition [Bansal A, 2006].

b. Among 218 patients aged 3 months to 19 years, 20% were reported to

be cases of treatment failure. Causes include clinical sepsis and

progressive pneumonia [Victor R, 2007].

c. Among 60 patients aged 3 months to five years, 23% was reported to be

treatment failure. Progressive pneumonia has been cited as the most

common cause at 57%. [Prada C, 2007]

d. Among 153 patients aged 1 month to 16 years, 9% was reported to be

treatment failure. Of these, 50% had evidence of mixed infection.

[Juve’n T,2004]

39

CQ 10. When can switch therapy in bacterial pneumonia be started?


Switch from intravenous antibiotic administration to oral form 2-3 days after I

nitiation of antibiotic is recommended in a patient [Grade D] who

[a] is responding to the initial antibiotic therapy,

[b] is able to feed with intact gastrointestinal absorption; and

[c] does not have any pulmonary or extrapulmonary complications.

UPDATE HIGHLIGHTS

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.

Annotation 10A. Comparative trial

Using clinical cure up to day 14 as the outcome measure among 21 patients aged

3 months to 5 years, no significant statistical difference exists between that with 7 days of

IV ampicillin versus 3 days IV ampicillin plus 4 days oral amoxicillin (p value > 0.05)

[Ochoa-Ragaza S,2004].

Using clinical cure up to day 7 as the outcome measure among 26 patients aged

3 months to 5 years on 3 days of IV ampicillin, no significant statistical difference exists

(p value = 0.6) between that with cotrimoxazole versus oral amoxicillin as step down

therapy (p value > 0.05) [Marquez W,2007]. The use of cotrimoxazole however is

discouraged because of high failure and resistance rates [Carlos CC,2003; Carlos CC, 2004;

Carlos CC,2005; Carlos CC,200;6 Kabra SK;2006].

40

CQ 11. What ancillary treatment can be given?


1. Among inpatients, oxygen and hydration should be given if needed [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 [Grade D].

3. In the presence of wheezing, a bronchodilator may be administered [Grade D].

UPDATE HIGHLIGHTS

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.

Annotation 11A. Fluid management

A. Increase fluid intake

In a Cochrane systematic review among ambulatory patients with acute

respiratory infection, no randomized controlled trials assessing the effect of

increasing fluid intake in acute respiratory infections were found [Guppy MPB,2005].

B. Fluid restriction

There are no controlled studies assessing the effect of restricting fluid intake

among patients hospitalized with pneumonia. In a Cochrane systematic review among hospitalized patients, the rate of

hyponatremia has been reported to be 31%-45% for nondehydrated children with

moderate to severe pneumonia [Guppy MPB, 2005]. Among 50 children aged 2–59 months with severe, and very severe pneumonia,

extracellular water [ECW] and plasma volume [PV] were moderately increased

[ECW 318 (45) vs 308 (49) ml/kg, PV 53.2 (2.3) vs 52.1 (2.3) ml/kg, p,0.05].

The SpO2 showed a significant linear relationship with ECW and PV (0.46 and

0.42 respectively, p =0.05) [Singhi S, 2005].

41

Annotation 11B. Cough preparation

A. In a Cochrane systematic review, one study performed exclusively in children

using three different mucolytics (bromhexine, ambroxol, neltenexine) demonstrated no

significant difference for the primary outcome of ’not cured or not improved’ (OR 0.40,

95% CI 0.10-1.62), and secondary outcome of ’no improvement’ (OR 0.34, 95% CI 0.09

to 1.36) [Chang CC, 2007].

B. Among ambulatory 62 children aged 3 month – 19 years, there was no statistical

difference in improving cough using verbal category Descriptive Scoring System

between the group on ambroxol and the group without treatment (p value > 0.05) [Alquiza

G,2006]

C. Among hospitalized 70 children aged 3 months – 19 years, there was no statistical

difference in decreasing respiratory rate and intercostal retractions between salbutamol,

normal saline solution and no treatment (p>0.05) [Gotos L,2004 ].

Annotation 11C. Micronutrients

A. In a Cochrane systematic review, five trials involving 1453 patients younger than

15 years old with non-measles pneumonia did not demonstrate significant difference

between those treated with adjunctive vitamin A and placebo as to mortality, measures of

morbidity, nor an effect on the clinical course of pneumonia (pooled odds ratio OR 1.49;

95% CI 0.66 to 3.35) [Ni J,2005].

B. In a systematic review of five double-blinded, randomized, controlled intervention

studies involving 2177 children aged 2-59 months children stratified according to basal

serum retinol concentration (<200 and >200 ug/L), the time to remission of 3 respiratory

signs was significantly lower in children with higher basal serum retinol concentrations in

the vitamin A group than in their counterparts in the placebo group [69.9+49.9 h

compared with 131.3+143.9 h; p value=0.049) [Brown N, 2004].

42

C. In a randomized controlled trial involving 287 children aged 2–59 months, with

pneumonia, no overall differences were observed between the group who received

vitamin A 50 000 IU (aged 2–12 mo) or 100 000 IU (aged 12–59 mo) and those who

received placebo [Rodriguez A,2005].

D. Among 187 children aged < 11 years hospitalized with 215 ALRI episodes, there was

no clinical benefit of supplementation with vitamin A, elemental zinc or the two

combined, compared with placebo in time to resolution of fever or tachypnea, or duration

of hospitalization. Children given elemental zinc had an increased risk of readmission for

ALRI within 120 days (relative risk [RR] 2.4; 95% CI 1.003–6.1) [Chang AB, 2006].

E. In a randomized controlled trial of patients aged 2-35 months admitted with severe

LRI, there is no difference between the groups who receive alpha-tocopherol 200 mg and

ascorbic acid 100 mg twice daily or placebo for 5 days as to time taken to recover from a

very ill status, fever, tachypnoea, and feeding difficulty [Mahalanabis D, 2006].

F. In a randomized trial of 299 patients aged 2-23 months, there were no clinical or

statistically significant differences in the duration of tachypnea, hypoxia, chest

indrawing, inability to feed, lethargy, severe illness, or hospitalization between those who

received 10-mg tablets of zinc sulfate versus placebo twice a day (p value = 0.015)

[Bose A, 2006].

G. In a randomized controlled trial 153 children aged 2–24 months who were hospitalized

with severe ALRI, recovery rates from very ill status and from fever in zinc treated boys

were 2.6 times (p= 0.004) and 3 times (p= 0.003) those in non-zinc-treated children;

feeding difficulty and tachypnea were not significantly different between groups after an

adjusted analysis. Recovery rates were not significantly different between groups on the

basis of vitamin A treatment [Mahalanabis D,2004].

H. In a randomized double-blind placebo-controlled clinical trial of 270 children aged

2-23 months, the group receiving elemental zinc (20 mg per day) had reduced duration of

severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of

chest indrawing (95% CI 0.80, 0.61-1.05), respiratory rate more than 50 per min (95% CI

0.74, 0.57-0.98), and hypoxia (95% CI 0.79, 0.61-1.04), and overall hospital duration

(95% CI 0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both

severe pneumonia and time in hospital [Brooks WA,2004].

43

Annotation 11D. Chest Physiotherapy

Summary of three [3] studies did not demonstrate any statistically significant difference

between the group who have undergone chest physiotherapy and the control group as to

time to improvement in chest xray, and the duration of the following parameters, namely

fever, cough and hospital stay (p value < 0.05) [Gilchris FJ,2007].

Annotation 11E. Alternative medicine

A. Virgin coconut oil

In a single blinded randomized controlled trial conducted to 40 children, the

group who received 2 ml/kg/day of virgin coconut oil orally taken for a

maximum period of three days had a respiratory rate normalizing earlier than the

control group (32.6 hrs (SD=21.73) versus 48.2 hrs (SD 17.62); p value = 0.017)

[Erquiza,2007].

B. Probiotic

Among 76 infants, probiotic OMX capsules had shorter duration of cough and

hospital stay with mean 2.4 + 1 days compared to control mean 4.3 + 1 day (p

value <0.007); resolution of tachypnea and retractions 1.5 + 0.5 days compared

to control 4.3+ 1 days (p value < 0.001); and tachypnea on day 3 as outcome

measure (RR 0.11; NNT 2) [Bayer-Mulsid,2006].

44

CQ 12. How can pneumonia be prevented?


1. Vaccines recommended by the Philippine Pediatric Society should be routinely

administered to prevent pneumonia [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 [Grade A].

3. Vitamin A [Grade A], immunomodulators [Grade D] and vitamin C [Grade D] should

not be routinely administered as a preventive strategy.

UPDATE HIGHLIGHTS

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

Annotation 12A. Immunomodulators

In a Cochrane systematic review involving thirty-four placebo-controlled trials

(3877 participants) aged less than 18 years old, the use of immunostimulants was shown

to reduce rates of acute respiratory infection by 40% (Weighted Mean Difference -

39.68%; 95% CI -47.27% to – 32.09%). Caution should be exercised in interpreting the

possible advantage of immunostimulant because the quality of trials that were included

in the meta-analysis was generally poor, and a high level of statistical heterogeneity was

evident [Del-Rio-Navarro,2006]. The number needed to prevent is 3.

45

Annotation 12B. Handwashing

Among 600 households who received handwashing promotion with either antibacterial

soap [plain soap with 1.2% triclocarban] or plain soap versus 306 households as controls

[without handwashing promotion], children younger than 5 years in households that

received handwashing promotion and soap had a 50% lower mean incidence of

pneumonia than controls ( -45% 95% CI -64% to -26% for antibacterial soap, and -50%

95%CI =65% to -34% for plain soap) [Luby SP,2005]. The number needed to prevent is 2.

Annotation 12C. Vaccine

A. Pneumococcal vaccine

• In a Cochrane systematic review, the pooled relative risk [RR] for x-ray

confirmed pneumonia with consolidation (of unspecified etiology) and clinical

pneumonia with or without x-ray confirmation from two articles were 0.78 (95% CI

0.69 - 0.89) and vaccine efficacy [VE] for x-ray confirmed pneumonia of 22% (95%

CI 11% - 31%) [Lucero MG, 2004].

• Comparing the rates in 2004 with those in the baseline period of 1997 to 1999

among children younger than 2 years, hospitalizations due to all-cause pneumonia

declined from 11.5 to 5.5 per 1000 children (52.4% decline; p<.001); and ambulatory

visits due to all-cause pneumonia declined from 99.3 to 58.5 per 1000 children

(41.1% decline; p<.001). Rates of hospitalizations due to pneumococcal pneumonia

declined from 0.6 to 0.3 per 1000 children (57.6% decline; p<.001) and rates of

ambulatory visits declined from 1.7 to 0.9 per 000 children (46.9% decline; p<.001)

[Zhou F, 2007].

• Among 1,555 patients aged 75–105 days (median 82 days), PCV-7 (n = 819) at 3,

5 and 11 months of age. radiologic pneumonia is less in the PCV-7 group than in the

control group (RR: 0.35; 95% CI: 0.22–0.53; p <0.0001) within 24 months

[Esposito S, 2007].

B. Hib vaccine

In 1293 children (431 cases, 862 controls) below 2 years, the risk for radiologic

pneumonia is OR 0.69; 95% CI 0.43 to 1.09 [Sampaio AL,2004]

46

Annotation 12 D. Micronutrients

In a randomized controlled trial of 1665 children aged 60 days to 12 months old, 70 mg

elemental zinc given orally once a week for 1 year compared with placebo led to a

significantly lower incidence of pneumonia in the zinc group than in the placebo group

(RR 0.83 95% CI 0.73-0.95) [Brooks WA,2005].

Annotation 12 E. Breastfeeding

15,890 infants who were exclusively breastfed had a large and statistically significant

reduction in risk for hospitalization for lower respiratory tract infection (adjusted OR:

0.66; 95% CI: 0.47–0.92) compared with those who were not breastfed [Quigley MA, 2007].

Annotation 12F. Gastric acid inhibitors

Among 186 GERD patients aged 8-16 months old on gastric acid inhibitors (10 mg/kg

ranitidine per day divided twice daily or 1 mg/kg omeprazole once a day) during 4 month

follow-up period, the risk to develop pneumonia is higher among those who are on

gastric acid inhibitors) than controls ( OR 6.39; 95% CI: 1.38–29.70) [Canani RB,2006].

47

Appendix A Development Process

Task Force on pCAP.

The Task Force on pCAP are as follows: Cristan Q. Cabanilla as the chair of the Task

Force, Gladys L. Gillera as the secretary, and Regina M. Canonizado, Anjanette R. de

Leon, Roslyn Marie K. Dychiao, Beatriz Praxedes I. Apolla Mandanas-Paz, Anna Marie

S. Putulin, Emily Dolores G. Resurreccion, Ana Maria A. Reyes, Marion O. Sanchez,

Rita Marie Lourdes S. Vergara and Rozaida R. Villon as members. A pediatric

radiologist, Dr Gerado L. Beltran has been invited to provide insight to radiologic

concerns.

There are no competing interests for any member of the pCAP Task Force except as

guest lecturers or reactors in a pharmaceutical industry sponsored scientific meeting

dealing with therapy.

Identification and appraisal of evidence.

Search strategies have included MeSH on each of the 12 clinical questions run on online

database [PubMed], the Philippine Pediatric Society publication and researches from

each of the six Philippine Academy of Pediatric Pulmonologists, Inc. accredited training

program in pediatric pulmonology. Literature search is limited to the following: [1]

articles published from January 2003 to December 2007; [2] English language;

[3] 3 months to 19 years of age; [4] and immunocompetent host. Inclusion of an article

was assessed by each subgroup to be adequate for appraisal.

External Review.

The update has been reviewed by pediatric pulmonologists who are not involved in the

development process, and subsequently approved by the PAPP Board of Directors.

Funding.

PAPP has exclusively funded the formulation of this update.

Disclaimer. As the update merely serves to inform the physician of recent evidence, it is not intended

to be a standard of care. Due to specific requirements imposed by individual children, the

physician is advised to exercise personal clinical judgment to the best interest of the

patient.

48

Appendix B. Definition of terms

Absolute risk (AR)

The probability that an individual will experience the specified outcome during a specified

period. It lies in the range 0 to 1, or is expressed as a percentage. In contrast to common usage,

the word "risk" may refer to adverse events or desirable events.

Absolute risk increase (ARI) The absolute difference in risk between the experimental and control groups in a trial. It is used

when the risk in the experimental group exceeds the risk in the control group, and is calculated

by subtracting the AR in the control group from the AR in the experimental group.

Absolute risk reduction (ARR) The absolute difference in risk between the experimental and control groups in a trial. It is used

when the risk in the control group exceeds the risk in the experimental group, and is calculated

by subtracting the AR in the experimental group from the AR in the control group.

Baseline risk

The risk of the event occurring without the active treatment. It is estimated by the baseline risk

in the control group.

Confidence interval (CI)

The 95% confidence interval (or 95% confidence limits) would include 95% of results from

studies of the same size and design in the same population. This is close but not identical to

saying that the true size of the effect (never exactly known) has a 95% chance of falling within

the confidence interval. If the 95% confidence interval for a relative risk (RR) or an odds ratio

(OR) crosses 1, then this is taken as no evidence of an effect.

Hazard ratio (HR) Broadly equivalent to relative risk (RR); useful when the risk is not constant with respect to

time. It uses information collected at different times. The term is typically used in the context

of survival over time. If the HR is 0.5 then the relative risk of dying in one group is half the

risk of dying in the other group.

Likelihood ratio The ratio of the probability that an individual with the target condition has a specified test

result to the probability that an individual without the target condition has the same specified

test result.

Meta-analysis A statistical technique that summarises the results of several studies in a single weighted

estimate, in which more weight is given to results of studies with more events and sometimes

to studies of higher quality.

Negative likelihood ratio (- LR)

The ratio of the probability that an individual with the target condition has a negative test result

to the probability that an individual without the target condition has a negative test result. This

is the same as the ratio (1-sensitivity/specificity).

Negative predictive value (NPV) The chance of not having a disease given a negative test result.

Number needed to harm (NNH) One measure of treatment harm. It is the average number of people from a defined population

you would need to treat with a specific intervention for a given period of time to cause one

additional adverse outcome. NNH can be calculated as 1/ARI.

Number needed to treat (NNT)

One measure of treatment effectiveness. It is the average number of people who need to be

treated with a specific intervention for a given period of time to prevent one additional adverse

outcome or achieve one additional beneficial outcome. NNT can be calculated as 1/ARR .

49

Odds ratio (OR) One measure of treatment effectiveness. It is the odds of an event happening in the

experimental group expressed as a proportion of the odds of an event happening in the control

group. The closer the OR is to one, the smaller the difference in effect between the

experimental intervention and the control intervention. If the OR is greater (or less) than one,

then the effects of the treatment are more (or less) than those of the control treatment. Note that

the effects being measured may be adverse (e.g. death or disability) or desirable (e.g. survival).

When events are rare the OR is analagous to the relative risk (RR), but as event rates increase

the OR and RR diverge.

Positive likelihood ratio (+LR) The ratio of the probability that an individual with the target condition has a positive test result

to the probability that an individual without the target condition has a positive test result. This

is the same as the ratio (sensitivity/1-specificity).

Positive predictive value (PPV)

The chance of having a disease given a positive test result

P value

The probability that an observed or greater difference occurred by chance, if it is assumed that

there is in fact no real difference between the effects of the interventions. If this probability is

less than 1/20 (which is when the P value is less than 0.05), then the result is conventionally

regarded as being "statistically significant".

Relative risk (RR)

The number of times more likely (RR > 1) or less likely (RR < 1) an event is to happen in one

group compared with another. It is the ratio of the absolute risk (AR) for each group. It is

analogous to the odds ratio (OR) when events are rare. Relative risk is the absolute risk (AR)

in the intervention group divided by the AR in the control group. It is to be distinguished from

odds ratio (OR) which is the ratio of events over non-events in the intervention group over the

ratio of events over non-events in the control group.

Relative risk increase (RRI) The proportional increase in risk between experimental and control participants in a trial.

Relative risk reduction (RRR) The proportional reduction in risk between experimental and control participants in a trial. It is

the complement of the relative risk (1-RR).

Sensitivity The chance of having a positive test result given that you have a disease

Specificity The chance of having a negative test result given that you do not have a disease

Statistically significant Means that the findings of a study are unlikely to have arisen because of chance. Significance

at the commonly cited 5% level (P < 0.05) means that the observed difference or greater

difference would occur by chance in only 1/20 similar cases.

Weighted mean difference (WMD)

A measure of effect size used when outcomes are continuous (such as symptom scores) rather

than dichotomous (such as death). The mean differences in outcome between the groups being

studied are weighted to account for different sample sizes and differing precision between

studies. The WMD is an absolute figure and so takes the units of the original outcome measure.

For more of glossary of EBM terms, please log on to http://cebm.net/toolbox.asp

50

Appendix C. Risk Classification for Pneumonia-Related Mortalitya

VARIABLES

PCAP A Minimal risk

PCAP B Low risk

PCAP C Moderate risk

PCAP D High risk

1. Co-morbid

illnessb

None Present Present Present

2. Compliant

caregiverc

Yes Yes No No

3. Ability to

follow-upc

Possible Possible Not possible Not possible

4 Presence of

dehydrationd

None Mild Moderate Severe

5. Ability to feed Able Able Unable Unable

6. Age

>11 mo >11 mo <11 mo < 11 mo

7. Respiratory ratee

2-12 months

1-5 years

> 5 years

>50/min

>40/min

>30/min

>50/min

>40/min

>30/min

>60/min

>50/min

>35/min

>70/min

>50/min

>35/min

8. Signs of resp failure

a. Retraction

b. Head bobbing

c. Cyanosis

d. Grunting

e. Apnea

f. Sensorium

None

None

None

None

None

Awake

None

None

None

None

None

Awake

Intercostal /

subcostal

Present

Present

None

None

Irritable

Supraclavicular/

intercostal/subcostal

Present

Present

Present

Present

Lethargic/stuporous/

comatose

9. Complications [effusion, pneumothorax]

None None Present Present

ACTION PLAN

OPDf

Follow-up

at end of

treatment

OPDf

Follow-up

after 3

days

Admit to

regular ward

Admit to a critical

care unit

Refer to specialist

aIn the presence of overlapping parameters, assume the next severe classification even with only one

parameter present. bComorbid illness includes malnutrition, asthma, congenital heart disease and other clinical conditions

that can directly affect respiratory function. cNonavailability of these external factors necessitates admission even if accompanied by less severe

parameters dGrading of dehydration adapted from Nelson’s Textbook of Pediatrics

1: 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 blood pressure, no urine output, very sunken eyes and fontanel, no

tears, parched mucous membranes, tenting of the skin, very delayed capillary refill, cold and mottled]

eWorld Health Organization age specific criteria for tachypnea

2

fParents should be advised that if patient is rapidly deteriorating, immediate follow-up is necessary

51

Appendix D. Bacterial Pneumonia Score

Predictor

Points

Axillary temp >39c 3

Age > 9 months 2

Absolute neutrophil

count >8,000/mm3

2

Bands > 5% 1

Chest x ray

Infiltrate

Location

Fluid in pleural space

Abscess, bullae or

pneumotocoele

Atelectasis

Well-defined, lobular, segmental,

subsegmental [rounded] 2 points

Poorly defined, patchy 1 point

Interstitial, peribronchial -1 point

Single lobe 1 point

Multiple lobes in

one or both lungs, but

well-defined infiltrates

as in above 1 point

Multiple sites, perihilar,

poorly defined: -1 point

Minimal blunting of angle 1 point

Obvious fluid 2 points

Equivocal 1 point

Obvious 2 points

Subsegmental [usually multiple sites] -1 point

Lobar, involving RML or RUL -1 point

Lobar, involving other lobes 0 point

-3 to 7

Moreno L, Krishnan JA, Duran P, and Ferrero F: Development and Validation of a Clinical Prediction Rule

to Distinguish Bacterial From Viral Pneumonia in Children. Pediatr Pulmonol 2006; 41:331-337

52

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