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PCAP Updates PDF
PCAP Updates PDF
PAPP PERSPECTIVE
Updates
in the
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: papp_office@yahoo.com.
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
2
CONTENTS
Foreword
Appendix
Bibliography
3
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.
4
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.
5
2004 CLINICAL PRACTICE GUIDELINE
CLINICAL QUESTIONS WITH RECOMMENDATIONS, AND
UPDATE HIGHLIGHTS WITH ANNOTATIONS
Evaluation
Treatment
Prevention
6
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].
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
7
CQ 1. Who shall be considered as having community-acquired pneumonia?
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]:
UPDATE HIGHLIGHTS
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.
8
Annotation 1A. Background.
a. There is one [1] study dealing with identifying patients with radiographic
pneumonia in the out-patient department
b. There is one [1] study dealing with identifying patients with radiographic
pneumonia in the combined out-patient department and emergency room
9
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 510 patients aged 2-59 months of age with cough and with any
one of the following [Mahabee-Gittens EM, 2005 ]:
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 ].
___________________________________________
*
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.
10
CQ 2. Who will require admission?
2004 Clinical Practice Guideline Recommendation
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].
11
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
UPDATE HIGHLIGHT
The low risk of bacteremia does not warrant blood culture determination in
nonsevere pneumonia.
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.
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].
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.
12
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?
UPDATE HIGHLIGHTS
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%.
13
Annotation 4A. Chest x-ray
1. Chest x-ray has been used as a tool to predict the type of pathogen
14
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].
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 109/L are
1.89 and 0.80, respectively [Korppi M, 2004].
b. Among 862 patients with proven RSV infection aged 62398 days,
WBC > 15,000 x 109/L, the probability of a concurrent serious bacterial
infection is 4.7% [Purcell K, 2007].
15
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, 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].
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].
16
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].
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].
17
CQ 5. When is antibiotic recommended?
2004 Clinical Practice Guideline Recommendation
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.
18
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%.
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
19
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].
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 84.6100) and 93.9% (95% CI 87.897.5) 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.
20
B. Individual clinical predictors
1. Age
21
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.
Age with
Author Age N + antibody titer for Prevalence
Year [Years] Mycoplasma sp and/or [%]
Chlamydia sp
[Years]
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) [Juven T, 2003].
22
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 109/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 days8 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].
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].
23
CQ 6. What empiric treatment should be administered if a bacterial etiology is
strongly considered?
2004 Clinical Practice Guideline Recommendation
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.
24
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]
25
Annotation 6B. Antibiotic resistance
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]:
Haemophilus No No No No 13% 10% 20% 14% 18% 36% 15% 16% 13% 10% 10% 9%
Influenzae data data data data
a
Screening with 1 ug oxacillin disc
26
Annotation 6C. Antibiotic regimen for PCAP A or B [non severe pneumonia]
A. Oral Amoxicillin
1. Comparative trial
27
2. Treatment regimen
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].
28
B. Other antibiotic options
1. Cotrimoxazole
29
ANNOTATION 6D. PCAP C or severe pneumonia
A. Monotherapy
B. Combination therapy
30
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].
31
7. Other treatment regimens
b. Chloramphenicol
C. Community-acquired MRSA
b. Vancomycin remains to be the first line therapy for severe infections possibly
caused by MRSA.
32
CQ 7. What treatment should be initially given if a viral etiology is strongly
considered?
UPDATE HIGHLIGHT
Influenza
Please refer to CQ 11. What ancillary treatment can be given? for recommendations
pertaining to ancillary treatment.
33
CQ 8. When can a patient be considered as responding to the current antibiotic?
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
A. Background
34
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
aged 2-59 months is 33-36 hours [Bansal A,2006].
Inability to feed
Average time of recovery from inability to feed among 71 children
aged 2-59 months is 33-36 hours [Bansal A,2006].
35
CQ 9. What should be done if a patient is not responding to current antibiotic
therapy?
UPDATE HIGHLIGHTS
1. There are no studies dealing with therapeutic interventions following
treatment failure among children having community-acquired pneumonia.
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;
36
Annotation 9A. Course of action in 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] :
B. Treatment failure
37
Annotation 9C. Causes of failure in the treatment of bacterial 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].
38
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
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.
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].
39
CQ 11. What ancillary treatment can be given?
1. Among inpatients, oxygen and hydration should be given if needed [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.
40
Annotation 11B. Cough preparation
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].
41
C. In a randomized controlled trial involving 287 children aged 259 months, with
pneumonia, no overall differences were observed between the group who received
vitamin A 50 000 IU (aged 212 mo) or 100 000 IU (aged 1259 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 1.0036.1) [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 224 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].
42
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].
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].
43
CQ 12. How can pneumonia be prevented?
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].
UPDATE HIGHLIGHTS
3. Single study showed that patients on gastric acid inhibitors are at an increase
risk to have pneumonia
44
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.
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 75105 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: 0.220.53; 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]
45
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: 0.470.92) compared with those who were not breastfed [Quigley MA, 2007].
46
Appendix A Development Process
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.
47
Appendix B. Definition of terms
48
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.
49
Appendix C. Risk Classification for Pneumonia-Related Mortalitya
OPDf OPDf
Follow-up Follow-up Admit to Admit to a critical
ACTION PLAN at end of after 3 regular ward care unit
treatment days Refer to specialist
a
In the presence of overlapping parameters, assume the next severe classification even with only one
parameter present.
b
Comorbid illness includes malnutrition, asthma, congenital heart disease and other clinical conditions
that can directly affect respiratory function.
c
Nonavailability of these external factors necessitates admission even if accompanied by less severe
parameters
d
Grading of dehydration adapted from Nelsons Textbook of Pediatrics1: 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]
e
World Health Organization age specific criteria for tachypnea2
f
Parents should be advised that if patient is rapidly deteriorating, immediate follow-up is necessary
50
Appendix D. Bacterial Pneumonia Score
Predictor Points
3
Axillary temp >39c
2
Age > 9 months
2
Absolute neutrophil
count >8,000/mm3
1
Bands > 5%
-3 to 7
Chest x ray
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
51
Bibliography
52
Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M,
Faruque AS, Black RE.Effect of weekly zinc supplements on incidence of
pneumonia and diarrhoea in children younger than 2 years in an urban, low-
income population in Bangladesh: randomised controlled trial Lancet.
2005;366(9490):999-1004
Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE
Zinc for severe pneumonia in very young children: double-blind placebo-
controlled trial. Lancet. 2004 ;363(9422):1683-8.
Butun Y, Kose S, Babayigit A, Olmez D Anali O, Uzuner N, Karaman O: Chlamydia and
Mycoplasma serology in respiratory tract infections of children Tberkloz ve
Toraks Dergisi 2006;54:254-258
Cabanilla C, Santos J. 2006 Purposive sampling questionnaire survey as to the utilization
of the 2004 Clinical Practice Guideline in Pediatric Commnity acquired
pneumonia. Conducted during Preconvention Workshop and a satellite symposia
43rd PPS Annual Convention. Unpublished.
Canani RB , Pia Cirillo, Paola Roggero, Claudio Romano, Basilio Malamisura,, Gianluca
Terrin, Annalisa Passariello Francesco Manguso, Lorenzo Morelli, Alfredo
Guarino, for the Working Group on Intestinal Infections of the Italian Society of
Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP): Therapy With
Gastric Acidity Inhibitors Increases the Risk of Acute Gastroenteritis and
Community-Acquired Pneumonia in Children Pediatrics; 2006;117:817-820
Carlos GP, Balitbit LJ, Nacpil AL, Lao-Abesamis MB: Comparison of Penicillin
G/Chloramphenicol and cefuroxime in the treatment of pneumonia in children.
2002-2005 Philippine Pediatric Society Philippine Pediatric Researches
2006;4:187
Carlos CC The Antimicrobial Resistance Surveillance Program Progress Report January-
December 2003. Research Institute of Tropical Medicine
Carlos CC The Antimicrobial Resistance Surveillance Program Progress Report January-
December 2004. Research Institute of Tropical Medicine
Carlos CC The Antimicrobial Resistance Surveillance Program Progress Report January-
December 2005. Research Institute of Tropical Medicine
Carlos CC The Antimicrobial Resistance Surveillance Program Progress Report January-
December 2006. Research Institute of Tropical Medicine
Castro AV, C.M. Nascimento-Carvalho, F. Ney-Oliveira, C.A. Arajo-Neto, S.C.S.
Andrade, L.L.S. Loureiro and P.O. Luz: Additional Markers to Refine the World
Health Organization Algorithm for Diagnosis of Pneumonia Indian Pediatrics
2005;42:773-781
Castro AV, Nascimento-Carvalho CM, Ney-Oliveira F Arau jo-Neto CA , Sandra C.
Andrade SC: Pulmonary Infiltrate Among Children With Cough and Tachypnea
The Pediatric Infectious Disease Journal 2006; 25:757
Chang CC, Cheng AC, Chang AB. 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 2007, Issue 4. Art. No.: CD006088.
DOI:10.1002/14651858.CD006088.pub2.
53
Chang AB, Paul J Torzillo, Naomi C Boyce, Andrew V White, Peter M Stewart, Gavin
R Wheaton, David M Purdie, John Wakerman and Patricia C Valery : Zinc and
vitamin A supplementation in Indigenous Australian children hospitalised with
lower respiratory tract infection: a randomised controlled trial MJA 2006; 184:
107112
Chantry CJ. Full breastfeeding duration and associated disease in respiratory tract
infection in US children. Pediatrics. 2006 Feb;117(2):425-32.
Chiang WC, Teoh OH, Chong CY, Goh A, Tang JP, Chay OM.:Epidemiology, clinical
characteristics and antimicrobial resistance patterns of community-acquired
pneumonia in 1702 hospitalized children in Singapore Respirology. 2007;12:254-
61
Cherian T, Mulholland K, Carlin JB, Ostensen H, Amin R, de Campo M, Greenberg
D, Lagos R, Lucero M, Madhi SA, OBrien KL, Obaro S, Steinhoff MC, and the
WHO Radiology Working Group: Standardized interpretation of paediatric chest
radiographs for the diagnosis of pneumonia in epidemiological studies Bulletin of
the World Health Organization 2005;83:353-359
de Andrade AL , Joo Guimares de Andrade, Celina Maria Turchi Martelli, Simonne
Almeida de Silva, Renato Maurcio de Oliveira, Maria Selma Neves Costa,
Cristina Borges Laval, Luiza Helena Vilela Ribeiro and Jose Luis Di Fabio:
Effectiveness of Haemophilus influenzae b conjugate vaccine on childhood
pneumonia: a case-control study in Brazil International Journal of Epidemiology
2004;33:173181
de Fatima M, SantAnna March, CC. Signs and symptoms indicative of CAP in
Infants under six months. Brazilian Journal of Infectious Diseases 2005;9:150-155
de Jesus-Oabel BA and Atienza-de Leon MN, Knowedge, attitude and practice of
physicians of the North Integrated Residency Training on the diagnosis and
management of community-acquired pneumonia in children.2008. Unpublished.
Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, Sienra-Monge J.Immunostimulants
for preventing respiratory tract infection in children. Cochrane Database Syst Rev.
2006 Oct 18;(4):CD004974.
de la Cruz R, de Guzman D, Cabanilla C, Santos J: Clinical indices predicting
pneumonia.Philippine Childrens Medical Center Book of Abstracts 2007;189
Don M, Fasoli L, Paldanius M, Marjaana Kleemola RV, Ra Ty R, Leinonen M, Korppi
M, Tenore A and Canciani M: Aetiology of community-acquired pneumonia:
Serological results of a paediatric survey Scandinavian Journal of Infectious
Diseases 2005;37:806-812
Don M, Valent F, Korpppi M, Falleti E, de Candias A, Fasoli L, Tenorei A and
Canciani M Efficacy of serum procalcitonin in evaluating severity of community-
acquired pneumonia in childhood. Scandinavian Journal of Infectious Diseases,
2007; 39: 129-137
Enarson P, Enarson D, Gie R International Union Against Tuberculosis and Lung
Disease. Management of the child with cough or difficult breathing: A Guide For
Low Income Countries 2nd Ed 2004
Erquiza GS, Ochoa-Ragaza RS, Reley M and Jiao AQ: The effect of virgin coconut oil
supplementation for CAP in children aged 3-60 months admitted at the Philippine
childrens Medical Center: a single blinded RCT. Philippine Childrens Medical
Center. Unpublished
54
Esposito S, Alessandro Lizioli, Annalisa Lastrico1, Enrica Begliatti, Alessandro Rognoni,
Claudia Tagliabue, Laura Cesati1, Vittorio Carreri and Nicola Principi: Impact on
respiratory tract infections of heptavalent pneumococcal conjugate vaccine
administered at 3, 5 and 11 months of age Respiratory Research 2007, 8:12:1-9
Fonseca F, Hoppu K, Rey LC, Amaral J, Qazi S: Comparing Pharmacokinetics of
Amoxicillin Given Twice or Three Times per Day to Children Older than 3
Months with Pneumonia Antimicrob Agents Chemother 2003;47:997-1001
Garcia MC, de Ocampo J, Maraiono J: Clinical and radiologic variations of
Mycoplasma pneumoniae in children Philippine Pediatric Society Philippine
Pediatric Researches 2002-2005; 186
Gavranich JB, Chang AB. Antibiotics for community acquired lower respiratory tract
infections (LRTI) secondary to Mycoplasma pneumoniae in children. Cochrane
Database of Systematic Reviews 2005, Issue 3. Art. No.: CD004875.
DOI:10.1002/14651858.CD004875.pub2.
Gilchrist FJ: Is the use of chest physiotherapy beneficial in children with community-
acquired pneumonia?Arch. Dis. Child. online 27 Jul 2007; doi: 10.1136/
adc.2007.127290
Gotos LV, Cabanilla C, Santos J: Randomized study on salbutamol or normal saline
solution as nebulizing solution versus no treatment among patients admitted with
pCAP at Philippine Childrens Medical Center. The Philippine Journal of
Pediatrics 2004;53:165-170
Guppy MPB, Mickan SM, Del Mar CB. Advising patients to increase fluid intake for
treating acute respiratory infections. Cochrane Database of Systematic Reviews
2005, Issue 4. Art. No.: CD004419. DOI: 10.1002/14651858.CD004419.pub2.
Hazir T, Nisar YB, Qazi SA, Khan SF, Raza M, Zameer S and Masood SA: Chest
radiography in children aged 2-59 months diagnosed with non-severe pneumonia
as defined by World Health Organization descriptive multicentre study in
Pakistan BMJ 2006;333;629-633
Hazir T, Qazi SA, Nisar B, S. Maqbool, R. Asghar, I. Iqbal, S. Khalid, S.
Randhawa, S. Aslam, S. Riaz, S. Abbasi: Can WHO therapy failure criteria for
non-severe pneumonia be improved in children aged 259 months? Int J Tubercl
Lung Dis 2006;10:924931
Hazir T. Comparison of standard versus double dose of amoxicillin in the treatment of
non-severe pneumonia in children aged 2-59 months: a multi-centre,double blind,
randomized controlled trial in Pakistan. Arch Dis Child 2007;92;291-297
Huang HH,. Zhang YY, Xiu QY, Zhou X Huang SG Q, Wang DM ,Wan F:
Community-acquired pneumonia in Shanghai, China: microbial etiology and
implications for empirical therapy in a prospective study of 389 patients Eur J
Clin Microbiol Infect Dis 2006; 25:369374
Hussain H, Waters H, Omer SB, Khan A, Baig IY, Mistry R and Halsey N The cost of
treatment for child pneumonias and meningitis in the Northern Areas of Pakistan
Int J Health Plann Mgmt 2006; 21: 229238.
Juven T, Ruuskanen O and Mertsola J: Symptoms and signs of community-acquired
pneumonia in children Scand J Prim Health Care 2003;21:5256.
55
Kabra SK, Lodha R, Pandey RM. Antibiotics for community acquired pneumonia in
children. Cochrane Database of Systematic Reviews2006, Issue 3. Art. No.:
CD004874. DOI:10.1002/14651858.CD004874.pub2.
Kafetzis A, Constantopoulos A, and Papadopoulos NG: Etiology of community-acquired
pneumonia in hospitalized school-age children: evidence for high prevalence of
viral infections Clinical Infectious Diseases 2004; 39:6816
Kaiser L, Wat C, Mills TM.: Impact of Oseltamivir Treatment on Influenza-Related
Lower Respiratory Tract Complications and Hospitalizations. Arch Intern Med.
2003; 163:1667-1672.
Kogan R, Martinez A, Rubilar L, Paya E, Quevedo I, Pupo H, Klgo, Giradi G and Castro-
Rodriquez JA: Comparative Randomized Trial of Azithromycin Versus
Erythromycin and Amoxicillin for Treatment of Community-Acquired
Pneumonia in Children Pediatric Pulmonology 2003; 35:9198
Korppi M: Non-specific host response markers in the differentiation between
pneumococcal and viral pneumonia: What is the most accurate combination ?
Pediatrics International 2004;46:545550
Lovera D, Arbo A. Treatment of childhood complicated community-acquired pneumonia
with amoxicillin/sulbactam J Chemother. 2005;17:283-8
Luby SP, Agboatwalla M, Feikin DR, Painter J, Billhimer W, Altaf A, Hoekstra RM.
Effect of handwashing on child health: a randomised controlled trial. Lancet.
2005; 66(9481):225-33.
Lucero MG, Dulalia VE, Parreno RN, Lim-Quianzon DM, Nohynek H, Makela H,
Williams G. Pneumococcal conjugate vaccines for preventing vaccine-type
invasive pneumococcal disease and pneumonia with consolidation on x-ray in
children under two years of age. Cochrane Database of Systematic Reviews 2004,
Issue 4. Art. No.: CD004977. DOI: 10.1002/14651858.CD0049
Lupisan SP, Ruutu P, Abucejo-Ladesma BP, et al Predictors of death from severe
pneumonia among children 2-59 months old hospitalized in Bohol:implications
for referral criteria at a first-level health facility Trop Med Int Health. 2007;12
(8):962-71
Lynch T, Platt R, Gouin S, Larson C and Patenaude Y. Can we predict which
children with clinically suspected pneumonia will have the presence of focal
infiltrates on chest radiograph? Journal of Pediatrics 2004; 113; 3186-e189
Mahabee-Gittens EM, Grupp-Phelan J, Brody AS, Donnelly LF, Allen Bracey SE,
Duma EM, Mallory ML and Slap GB: Identifying children with pneumonia in the
emergency department. Clin Pediatr (Phila), 44(5): 427-35, 2005
Mahalanabis D, Madhurima Lahiri, Dilip Paul, Susham Gupta, Atul Gupta, Mohammed
A Wahed, and Mohammed A Khaled: Randomized, double-blind, placebo-
controlled clinical trial of the efficacy of treatment with zinc or vitamin A in
infants and young children with severe acute lower respiratory infection Am J
Clin Nutr 2004;79:4306
Mahalanabis D, Basak M, Paul D, Gupta S, Shaikh S, Wahed MA, Khaled MA
.Antioxidant vitamins E and C as adjunct therapy of severe acute lower-
respiratory infection in infants and young children: a randomized controlled trial.
Eur J Clin Nutr. 2006;60(5):673-80.
56
Marquez W Cabanilla C Cotromoxazole compared with amoxicillin as switch therapy in
moderate risk pediatric community-acquired pneumonia: a randomized controlled
trial.The Philippine Pediatric Society, Inc. 44th Annual Convention Research
Paper Abstract. 2007; 104
Matheson NJ, Harnden AR, Perera R, Sheikh A, Symmonds-Abrahams M.: Neuramidase
inhibitors for preventing and treating influenza in children (Review). Cochrane
Database of Systematic Reviews 2007, Issue 1. Art No.: CD002744.
Michelow I, Olsen K, Lozano J,Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen
M and McCracken GH Epidemiology and clinical characteristics of community-
acquired pneumonia in hospitalized children Pediatrics 2004;113;701-707
Mohamed Azmi Ahmad Hasal i , Mohamed I zham Mohamed Ibrahim, Syed Azhar Syed
Sulaiman, Zhar i Ahmad and J ameela Banu Ahmad Hasal i A clinical and
economic study of community-acquired pneumonia between single versus
combination therapy Pharm World Sci 2005; 27:249253
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.
Morozumi M: Simultaneous Detection of Pathogens in Clinical Samples from Patients
with Community-Acquired Pneumonia by Real-Time PCR with Pathogen-
Specific Molecular Beacon Probes Journal of Clinical Microbiology
2006,44:14401446
Morozumi M, Hasegawa K, Kobayashi R, Inoue N, Iwata S, Kuroki H, Kawamura N,
Nakayama E, Tajima T, Shimizu K, Ubukata K.Emergence of macrolide-resistant
Mycoplasma pneumoniae with a 23S rRNA gene mutation Antimicrob Agents
Chemother. 2005;49:2302-6
Ni J, Wei J, Wu T. Vitamin A for non-measles pneumonia in children. Cochrane
Database Syst Rev. 2005 Jul 20;(3):CD003700
Nunes A, Camargos P, Costa P Campos TK :Antigen Detection for the Diagnosis
of Pneumonia Pediatric Pulmonology 2004;38:135139
Othman N, D Isaacs and A Kesson1: Mycoplasma pneumoniae infections in Australian
children J. Paediatr. Child Health 2005; 41, 671676
Ochoa-Ragaza S, Gotos LV, Cabanilla C, Santos J: A preliminary study on switch
therapy among patients with pCAP The Philippine Journal of Pediatrics
2004;53:198-204
Ocbina Pollienette JR, Cabanilla C.Accuracy of the clinical predictors of
community-acquired pneumonia in Filipino Children aged 5-12 years old.
Philippine Pediatric Society Book of Abstracts 2006:140
Paintsil E: Pediatric community-acquired methicillin-resistant Staphylococcus aureus
infection and colonization: trends and management Curr Opin Pediatr
2007;19:7582
Pablo Brockmann V., Ximena Ibarra G., Ignacia Silva W. y Tamara Hirsch B.
Etiology of acute fever without source in infants consulting at an emergency
department Rev Chil Infect 2007; 24 (1): 33-39
PhilHealth, Health Technology Assessment Unit,Quality Assurance Research and Policy
Development Group HTA Forum 2006;4 4[1]:4
57
Philippine Health Insurance Corporation, Claims payment summary for CY 2006 ages 0-
19 for pneumonia. Personal communication
Pocsidio C, Melgar T, Beltran R, Cabanilla C. Outcome of patients with pCAP
evaluated and managed using the risk classification scheme of the PPS 2004 CPG
Philippine Childrens Medical Center. Unpublished
Prada C, Cabanilla C : Causes of early treatment failure among hospitalized
patients with pCAP. Philippine childrens Medical Center Book of Abstracts
2007;192
Purcell K ,MD, PharmD, MHA;Fergie J,MD. Epidemic of Community-Acquired
Methicillin-Resistant Staphylococcus aureus Infections. A 14-Year Study at
Driscoll Childrens Hospital. Arch Pediatr Adolesc Med.2005;159:980-985
Purcell K, Fergie J: Lack of Usefulness of an Abnormal White Blood Cell Count for
Predicting a Concurrent Serious Bacterial Infection in Infants and Young Children
Hospitalized With Respiratory Syncytial Virus Lower Respiratory Tract Infection
Pediatr Infect Dis J 2007;26:311315
Quigley MA: Breastfeeding and hospitalization for diarheal and respiratory infection in
the United Kingdom Millenium Cohort Study. Pediatrics. 2007
Apr;119(4):e837-42.
Rattanadilok Na, Bhuket T, Nawanoparatkul S, Suwanjutha S, Teeyapaiboonsilpa
P.Economic burden in management of acute lower respiratory infection, patients
perspective:a case study of Takhli District Hospital. 2002 J Med Assoc Thai 85
(Suppl. 4): S12411245.
Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H on behalf of WHO Child Health
Epidemiology Reference Group Global estimate of the incidence of clinical
pneumonia among children under five years of age Bulletin of the World Health
Organization 2004;82:895-903.
Requejo HI. Community-Acquired Pneumonia in the Childhood: Analysis of the
Diagnostic Methods The Brazilian Journal of Infectious Diseases 2007;11:246-
248.
Requejo H, Cocoza MA C-Reactive Protein in the Diagnosis of Community-Acquired
Pneumonia The Brazilian Journal of Infectious Diseases 2003;7:241-244
Rodrguez A, Davidson H Hamer, Jos Rivera, Mario Acosta, Gilda Salgado, Martha
Gordillo, Myryam Cabezas, Carlos Naranjo-Pinto, Julio Legusamo, Dinor
Gomez, Guillermo Fuenmayor, Edgar Jativa, Gladys Guaman,Bertha Estrella,
and Fernando Semprtegui Effects of moderate doses of vitamin A as an adjunct
to the treatment of pneumonia in underweight and normal-weight children: a
randomized, double-blind, placebo-controlled trial
Am J Clin Nutr 2005;82:10906.
Romulo AC, Lomibao-Santos MAA, Marcelo MJ, Cabanilla CQ, Santos J Randomized
trial comparing the efficacy and safety of oral amoxicillin and erythromycin in the
treatment of pCAP in an ambulatory setting. PCMC,2006 [Unpublished]
Rattanadilok Na, Bhuket T, Nawanoparatkul S, Suwanjutha S, Teeyapaiboonsilpa
P.Economic burden in management of acute lower respiratory infection, patients
perspective:a case study of Takhli District Hospital. 2002 J Med Assoc Thai 85
(Suppl. 4): S12411245.
58
Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H on behalf of WHO Child Health
Epidemiology Reference Group Global estimate of the incidence of clinical
pneumonia among children under five years of age Bulletin of the World Health
Organization 2004;82:895-903.
Sadang-Saguinsin S, Yu-Go O, Ochoa-Ragaza, S, Manalili A, Banzali K, Cabanilla C,
Santos J:Risk factors for mortality among pediatric patients admitted because of
community-acquire pneumonia. 2002-2005 Philippine Pediatric Society
Philippine Pediatric Researches 2006;4:196
Shah S, Alpern E, Zwerling L Risk of Bacteremia in young children with pneumonia
treated as outpatients Arch Paediatr Adolesc Med 2003;157:389-392
Shelburne S., Musher D. In vitro killing of community-associated methicillin-resistant
Staphylococcus aureus with drug combinations. Antimicrobial Agents and
Chemotherapy, 2004;48:4016
Shoham Y, Dagan R, Givon-Lavi N, Liss Z, T, Shagan, Zamir O and Greenberg D
Community-Acquired Pneumonia in Children: Quantifying the Burden on
Patients and Their Families Including Decrease in Quality of Life Pediatrics
2005;115;1213-121
Strategies for Clinical Management of MRSA in the community: Summary of an
Experts meeting convened by the Centers for Disease Control and Prevention.
March 2006
Song JH , Hyun-Ha Chang, Ji Yoeun Suh, Kwan Soo Ko, Sook-In Jung, Won Sup
Oh, Kyong Ran Peck, Nam Yong Lee, Yonghong Yang, Anan Chongthaleong,
Nalinee Aswapokee, Cheng-Hsun Chiu, M. K. Lalitha Jennifer Perera, Ti Teow
Yee, Gamini Kumararasinghe, Farida Jamal, Adeeba Kamarulazaman1,
Navaratnam Parasakthi1, Pham Hung Van, Thomas So and Tak Keung Ng on
behalf of the ANSORP Study Group Macrolide resistance and genotypic
characterization of Streptococcus pneumoniae in Asian countries: a study of the
Asian Network for Surveillance of Resistant Pathogens (ANSORP) Journal of
Antimicrobial Chemotherapy 2004;53:457463
Sunit Singhi, Arvin Sharma and S Majumdar: Body water and plasma volume in severe
community-acquired pneumonia: implications for fluid therapy Annals of
Tropical Paediatrics 2005; 25:243252
Swingler GH: Observer variation in chest radiography of acute lower respiratory
infections in children: a systematic review. BMC Medical Imaging 2001; 1:1
Tajima T, Nakayama E, Hirai YKF, Ito H, Iitsuka T, Momomura M, Kutsuma H, Funaki
YKN, Yanagawa Y, Ubukata K: Etiology and clinical study of community-
acquired pneumonia in 157 hospitalized children J Infect Chemother 2006;
12:372379
Tsai MH, Yhu-Chering Huang, Chih-Jung Chen, Pen-Yi Lin, Luan-Yin Chang, Cheng-
Hsun Chiu, Kuo-Chien Tsao, Chung-Guei Huang, Tzou-Yien Lin: Chlamydial
pneumonia in children requiring hospitalization: effect of mixed infection on
clinical outcomeMicrobiol Immunol Infect 2005;38:117-122.
Tsolia MN, Psarras S, Bossios A, Audi H, Paldanius M, Gourgiotis D, Kallergi K,
Kafetzis A, Constantopoulos A, and Papadopoulos NG: Etiology of community-
acquired pneumonia in hospitalized school-age children: evidence for high
prevalence of viral infections Clinical Infectious Diseases 2004; 39:6816
59
Taina Juve n Jussi Mertsola Matti Waris Maija Leinonen Olli Ruuskanen:
Clinical response to antibiotic therapy for community-acquired pneumonia
Eur J Pediatr 2004;163: 140144
Taina Juven, Olli Ruuskanen and Jussi Mertsola Symptoms and signs of
community-acquired pneumonia in children Scand J Prim Health Care
2003;21:5256.
Toan NV, Khe ND, Hojer B.. Expenditure and payment sources for treating acute
respiratory infections in rural Vietnam. Southeast Asian J Trop Med Public Health
200132(4):682688.
Victor R, Ochoa-Ragaza S, Saguinsin-Sadang S, Yu O, Cabanilla C Santos J.
Early treatment failure and death among hospitalized patients with pCAP: a nine
year review. Philippine Childrens Medical Center Book of Abstracts. 2007;188
Whitney CG Effectiveness of seven-valent pneumococcal conjugate vaccine against
invasive pneumococcal disease: a matched case control study. Lancet. 2006;368
(9546): 1495-502
World Health Organization. Acute respiratory infections in children: case management
in small hospitals in developing countries. WHO/ARI/90.5. Geneva, Switzerland:
WHO, 1990.
World Health Organization Pneumonia Vaccine Trial Investigators Group:
Standardization of interpretation of chest radiographs for the diagnosis of
pneumonia in children, WHO 2001
Zeba A. Rasmussen, Abdul Bari, Shamim Qazi, Gul Rehman, Iqbal Azam,
SherBaz Khan, Farida Aziz, Sadia Rafi, Mehr Taj Roghani, Imran Iqbal, Abdul
Ghaffar Nagi, Waqar Hussain, Nahida Bano, late J.C. van Latum, & Mushtaq
Khan for the Pakistan COMET (Cotrimoxazole Multicentre Efficacy Trial) Study
Group Randomized controlled trial of standard versus double dose cotrimoxazole
for childhood pneumonia in Pakistan Randomized controlled trial of standard
versus double dose cotrimoxazole for childhood pneumonia in Pakistan Bulletin
of the World Health Organization 2005;83:10-19
Zhou F, PhD; Moe H. Kyaw, PhD; Abigail Shefer, MD; Carla A. Winston, PhD, MA; J.
Pekka Nuorti, MD, DSc Health Care Utilization for Pneumonia in Young
Children After Routine Pneumococcal Conjugate Vaccine Use in the United
States Arch Pediatr Adolesc Med. 2007;161(12):1162-1168
60