Children Pneumonia
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Transcript of Children Pneumonia
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Guidelines for the Management of Community-
Acquired Pneumonia in Children
PING-INGLEE 1, CHENG-HSUNCHIU2, PO-YENCHEN3, CHIN-YUNLEE 1, TZOU-YIENLIN2AND
Taiwan Pediatric Working Group for Guideline on the management of CAP in children 4
I. ETIOLOGY
A. The prevalent pathogen is different in different age
groups.
B. Atypical pneumonia
1. Viral infections prevail in children younger than
5 years of age, especially respiratory syncytial
virus. Other viral etiologies include influenzavirus, parainfluenza virus, adenovirus, human
metapneumovirus, rhinovirus, and cytomegalovirus.
2.Mycoplasma pneumoniae infections prevail in
children older than 2-5 years of age. M. pneumoniae
and Chlamydophila pneumoniaeare responsible
for 40-50% of atypical pneumonia in children of this
age in Taiwan. Legionella pneumophilainfection
is relatively uncommon in children. Chlamydia
trachomatisinfection may occur in children younger
than 6 months of age.
C. Pyogenic bacterial pneumonia
1. Streptococcus pneumoniae is the single most
common cause of pyogenic bacterial pneumoniain children beyond the first few weeks of life.
Haemophilus influenzae type b, Staphylococcus
aureus are also possible offending bacteria
pathogens in children younger than 5 years.
2. S. aureusis one common pathogen in pneumonia
associated with chest trauma or influenza virus
infection.
D.Mycobacterium tuberculosisinfection is still prevalent
in Taiwan and should be put into the list of differential
diagnoses for community-acquired pneumonia (CAP)
in children.
E. Mixed infection is not uncommon in children with
CAP.
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine1,
Taipei, Taiwan; Division of Infectious Diseases, Department of Pediatrics, Chang Gung Childrens Hospital, Chang
Gung Memorial Hospital, Chang Gung University, College of Medicine2, Taiwan; Section of Pediatric Infectious Diseases,
Department of Pediatrics, Taichung Veterans General Hospital3, Taichung; Taiwan Pediatric Working Group for Guideline
on the management of CAP in children 4 : Chin-Yun Lee, Ping-Ing Lee, Frank Leigh Lu, Li-Min Huang, Wu-Shi-
un Hsieh, Ren-Bin Tang, Wen-Jue Soong, Chih-Chien Wang, Fu-Yuan Huang, Rey-In Lien, Cheng-Hsun Chiu, Yhu-
Chering Huang, Kin-Sun Wong, Po-yen Chen, Ching-Chuan Liu, Kao-Pin Hwang, Yung-Zen Lin.
Received: June 7, 2007. Revised: July 7, 2007. Accepted: August 7, 2007.
Address reprint requests to: Dr. Tzou-Yien LIN, 5-7 Fu-Hsin Street, Kweishan333, Taoyuan, Taiwan.
E-mail: [email protected]
167
The causes of community-acquired pneumonia (CAP)
in children as reported in the medical literature must be
interpreted with caution, largely because many methods
for assignment of etiology are inadequate. Pyogenic
bacteria present the most difficult challenge, because
the normal upper respiratory tract flora frequently contains
potential pathogens and sputum collection may be difficult
in young children. The presence of bacteremia confirmsthe cause, but blood culture is positive in less than one
tenth of children with bacterial pneumonia.1
Epidemiologic information frequently is useful in
guiding the search for the cause of pneumonia. Certain
viruses, particularly respiratory syncytial virus (RSV),
rhinoviruses, and influenza virus, as well asMycoplasma
pneumoniae, are strongly seasonal in temperate areas.
However, as being located in subtropical region, the
seasonal tendency of these pathogens in Taiwan is not
as obvious as that in temperate areas.2,3In other instances,
the pattern of family illness can hint at the cause,
especially the highly contagious influenza virus. Table
1 lists the etiological agents for pneumonia in children,and Table 2 shows the distribution of these agents in
children by age.
Respiratory viruses are the most common cause of
CAP in children younger than 5 years old. RSV is most
prevalent in children younger than 1-2 years of age.4
Adenovirus has been reported to be associated with severe
diseases in Taiwan.5 In temperate areas, RSV and
influenza virus infections occur in winter epidemics, and
parainfluenza viruses and rhinoviruses are more common
in autumn and spring. Infections due to adenoviruses
occur throughout the year. However, a recent study in
Taiwan showed that monthly distribution of RSV
infections in Northern Taiwan showed a bimodal pattern
Review Article
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streptococcal pneumonia are rapidly progressive and
severe, frequently leading to hypoxemia and effusion
within hours. Mycobacterium tuberculosisthat is still
prevalent in Taiwan should be put into the lis t of
differential diagnoses for CAP in children.15
II. CLINICAL MANIFESTATIONS
A. Features of pyogenic bacteria pneumonia
1. Sudden deteriorated respiratory condition after an
apparently mild respiratory infection.
2. Severely debilitated with poor activity when the
body temperature is normal.
3. Tachypnea (respiratory rate > 60/min for infants
< 11 months, > 40/min for children between 1 year
and 4 years, and > 30/min for children older than
5 years).4. Oxygen saturation 92%, cyanosis.
5. Septic signs, such as consciousness disturbance,
bleeding tendency, and hypotension.
6. Signs of respiratory distress, including nasal flaring,
grunting, and chest wall retraction.
7. Lung consolidation, cavity formation.
B. Features of atypical pneumonia:
1. Children retain normal activity without features of
pyogenic bacteria pneumonia.
2. Conjunctivitis, otitis media, skin rash, and
wheezing may be more common.
There have been many studies conducted in an effortto differentiate bacterial etiologies of pneumonia from
viral infections based on clinical manifestations. In
general, none of the symptoms or signs can be considered
specific. The onset of pyogenic bacterial pneumonia may
be abrupt and may follow days of mild viral respiratory
illness. The patient is ill, sometimes toxic appearing.
Tachypnea, respiratory distress, hypoxemia, and lung
consolidation or cavity formation are predictive of severe
or pyogenic bacteria pneumonia16-18 A study from
developing world showed that oxygen desaturation was
associated with a greater risk of death, and tachypnea
is closely related to hypoxemia.19Several scoring systems
have been proposed to predict the severity and mortalityof CAP However, none of them has been modified
for children, and none has been examined in pediatric
patients.19,20
In contrast to pyogenic bacterial pneumonia, children
with atypical pneumonia, including those caused by
M. pneumoniae, C. pneumoniae, L. pneumophila
and viruses, usually appear healthy without apparent
respiratory distress. Presence of arthralgia and erythema
multiforme may suggestM. pneumoniaeinfection. As
compared with pyogenic bacterial pneumonia, some
studies suggest that children with atypical pneumonia
may have a higher incidence of conjunctivitis,21otitis
media,21and wheezing.22,23However, some features
thought to be specific for viral illness were not observed
more frequently in children with atypical pneumonia,
including rhinorrhea, illness in family members, and
myalgia.22,23
III. DIAGNOSIS
A. Acute phase reactants cannot reliably differentiate
between pyogenic bacterial pneumonia and atypical
pneumonia in children.
B. Image studies:
1. Chest radiography
a. Chest radiography should be considered in
children with an unexplained fever after excludingthe possibility of common infectious diseases,
and in those with a prolonged fever.
b. Chest X-ray findings can hardly differentiate
among different etiologies. Bulging interlobar
fissures and cavitations are suggestive of pyogenic
bacteria infection.
2. Chest ultrasonography is useful to evaluate the
presence of consolidation and pleural effusion, and
is helpful to guide thoracocentesis or chest tubing.
3. Computerized tomography of the chest may provide
details of pneumonia, and is indicated before
surgical interventions.
C. Microbiological investigations:1. Sputum:
a. Gram stain, and acid-fast stain if necessary,
should be done before the initiation of antibiotics.
b. The result of sputum culture may not represent
the true etiology of pneumonia. However,
with a qualitative count of gram stain
(polymorphonuclear cells > 25/high-power field
and epithelium < 10/ high-power field, with or
without phagocytosis of polymorphonuclear cells),
it does provide some help to adjust the
antimicrobial agent during the disease course.
c. For patients with suspectedM. tuberculosis
infection, acid-fast stain and mycobacteria cultureof the sputum should be done for at least 3 times.
For children whose sputum is not available,
gastric lavage for mycobacterial examination
should be done in the early morning before meals
for 3 consecutive days.
d. Direct fluorescent antigen test is available for
L. pneumophila.
2. Nasopharyngeal or oropharyngeal swab: The
specimens may be sent for virus culture and viral
antigen detection that are more useful for young
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children.
3. Blood culture should be performed in all children
with suspected pyogenic bacterial pneumonia.
4. A high titer of cold agglutinin may suggest
mycoplasma pneumonia. However, its specificity
is low.
5. A 4-fold rise of specific serum IgG titer or a single
positive IgM response indicates acute infection.
6.Urinary antigen tests are available for L.
pneumophila serogroup I and S. pneumoniae.
Although the pneumococcal antigen test is less
specific in children, it has a good negative
predictive value for the diagnosis of S. pneumoniae
pneumonia.
7. Tuberculin skin test should be performed whenM.
tuberculosis infection is suspected.
C. Invasive procedures:
1. The pleural fluid from thoracocentesis should betested for:
a. White count and differentials, protein, sugar,
lactate dehydrogenase and pH value.
b. Gram stain and acid-fast stain.
c. Antigen test for S. pneumoniae and H.
influenzaetype b may be helpful.
d. Culture for bacteria and, if suspected, virus and
M. tuberculosis .
2. Bronchoalveolar lavage and lung biopsy may be
considered in some difficult cases.
White cell count, neutrophil count, percentage of
immature neutrophil, erythrocyte sedimentation rate, andC-reactive protein (CPR) may reflect the severity of
infections, and are therefore believed to be able to
differentiate between pyogenic and nonpyogenic infections.
However, serum CRP was not useful to distinguish
between pneumococcal, chlamydial, or viral etiology
in children with pneumonia in a prospective study.24
Following an acute-phase stimulus, CRP values peak
at approximately 48 hours.25Timing of CRP test should
be considered in interpretation. Acute phase reactants
may only be useful to monitor the treatment response,
and to distinguish between fever and hyperthermia that
is not caused by an inflammatory response.
There has been some debates about the optimal timingfor chest X-ray examination in children with respiratory
symptoms. One study of 522 children aged 2 to 59 months
that were randomly allocated to have a chest radiograph
or not showed that there was a marginal improvement
in time to recovery which was not clinically significant.
It was concluded that routine use of chest radiography
is not beneficial in ambulatory children aged over 2 months
with acute lower respiratory-tract infection.26Another
study of 278 children aged 5 years or less suggested that
chest radiography should be considered a routine
diagnostic test in children with a temperature of 39
or greater and white count of 20,000/mm3or greater
without an alternative major source of infection. In that
study, pneumonia was found in 32 of 79 (40%) of those
with findings suggestive of pneumonia and in 38 of 146
(26%) of those without clinical evidence of pneumonia.27 Although chest radiography should not be performed
routinely in children with mild uncomplicated acute lower
respiratory tract infection,18it may be indicated in selective
patients, including an unexplained fever after excluding
the possibility of common infectious diseases, and a
prolonged fever with or without respiratory manifestations.
Chest X-ray findings can hardly differentiate among
different etiologies, especially for interstitial infiltrations
and pneumonic patches. Lung consolidation and pleural
effusion may be observed in pyogenic bacterial pneumonia
and pneumonia caused by M. pneumoniae , C.
pneumoniae, andL. pneumophila.
6
Bulging interlobarfissures and cavitations are suggestive of pyogenic bacteria
infection.28,29
Chest ultrasonography is simple, ready to use, and
not associated with radiation. It is useful to evaluate
the presence of consolidation and pleural effusion, and
is helpful to guide thoracocentesis or chest tubing, and
for follow-up. Therefore, it may be considered when
chest X-ray shows the presence of consolidation or pleural
effusion.
Computerized tomography (CT) of the chest may
provide details of pneumonia, including the extent of
consolidation, cavitation, lung abscess, and empyema.
It is indicated before surgical interventions, such as video-assisted thoracoscopic surgery (VATS), and decortication
of empyema. It may also be useful to evaluate complicated
pneumonia with poor clinical response. High-resolution
CT has been suggested to be more sensitive than chest
radiograph to detect pulmonary infiltrates.30However,
it should not be used routinely.
For the majority of patients treated as outpatients,
a specific microbiological diagnosis may not be necessary.
The investigations are important for patients admitted
to hospital with pneumonia. Sputum gram staining,
and acid-fast staining if necessary, should be performed
before the initiation of antibiotics. The sputum may be
hard to be obtained in children and the result of sputumculture may not represent the true etiology of pneumonia.
However, with a quantitative count of gram stain, it
does provide some help to adjust the antimicrobial agent
later on.
In Taiwan, it is recommended that at least 3 sputum
specimens should be sent for acid-fast stain and
mycobacterial culture in patients with suspected M.
tuberculosisinfection. Because the sputum cannot be
obtained in many children, gastric lavage in the early
morning before meals for 3 consecutive days is also
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a proper specimen for mycobacteria study.31
Direct fluorescent antigen test is a reliable test for
L. pneumophila. It may be performed in selected
patients. Sputum obtained from bronchoscope has better
sensitivity.
Because viral etiologies are more prevalent in younger
children with CAP, nasopharyngeal or oropharyngeal
swab may be sent for virus culture and viral antigen
detection, including RSV, influenza virus A and B,
parainfluenza virus, and adenovirus. However, laboratory
quality should be certificated for these tests.
Blood culture should be performed in all children
with suspected bacterial pneumonia before receiving
antibiotics. However, the isolation rate is no more than
10-20%.32In older children, 2 blood cultures may be
attempted to increase the diagnostic sensitivity.32
Cold agglutinin is a nonspecific antibody response
inM. pneumoniaeinfection. It is a sensitive test, butits specificity is low and an elevated titer may also be
seen in other causes of CAP. Several serological tests
are available for the diagnosis of M. pneumoniae,
Chlamydophila pneumoniae, Chlamydia trachomatis,
L. pneumophila, and common respiratory viruses. A
4-fold rise of IgG titer or a single positive IgM response
indicates acute infection. A single high titer of IgG is
not diagnostic.
Legionella uninary antigen test identifies only L.
pneumophilaserogroup I, which is claimed to be the
most common type causing clinical illness. A study in
Taiwan showed that urine antigen test can detect only
17.3% of 237 patients with L. pneumophila infection.33A negative test does no exclude the diagnosis.
Pneumococcal urinary antigen test is an acceptable
test to augment diagnostic methods for S. pneumoniae
infection. The sensitivity ranged between 50% and 80%,
and the specificity is about 90% in adults.34,35Studies
involving children have documented the lack of specificity.36,37Although many authors suggest that a low specificity
of the test may be attributed to that the test may give
a false-positive result in children with colonization, it
is more appropriate to say that the test may also be positive
in S. pneumoniaeinfections other than pneumonia,
such as otitis media.38The test has a high sensitivity
and a good negative predictive value for the diagnosisof S. pneumoniaepneumonia in children.
Bacille Calmette-Gurin (BCG) is routinely given
to children in Taiwan. Although the vaccination may
interfere with the interpretation of tuberculin reaction,
studies in Taiwan showed than BCG vaccination did not
appear to limit the usefulness of tuberculin skin test as
a tool for diagnosing tuberculosis.39 The tuberculin
reactivity toward BCG is usually lost 5-10 yr after
vaccination.40
Significant pleural effusion should be aspirated for
etiological diagnosis, especially when the effusion is
> 10 mm in thickness on the lateral decubitus view or
chest ultrasonography.32,41Gram stain and acid-fast stain
should be routinely done. White count and differentials,
protein, sugar, lactate dehydrogenase and pH value are
helpful to differentiate among transudate, and
uncomplicated or complicated parapneumonic pleural
effusions.41 The sensitivity of culture to define the
offending bacteria is usually limited but can be improved
by antigen detection.42,43Culture for M. tuberculosis
and viruses, though being less frequently seen, should
be done in suspected cases.
Invasive procedures, including bronchoalveolar lavage
and lung biopsy, should not be routinely done. Analysis
of sputum from bronchoalveolar lavage may have a better
correlation with pneumonia. However, it is technically
difficult in young children and can only be considered
in some difficult cases.
IV. GENERAL MANAGEMENT
A. Decision for hospitalization
1. Children with the following conditions that may
be suggestive of a grave illness are not recommended
to be cared at home:
a. Features of severe bacterial pneumonia (see II-
A).
b. Signs of dehydration.
c. Neonates and children with immunodeficiency.
d. Caretakers not able to provide appropriateobservation or supervision.
2. If the clinical condition is aggravated, or is not
improving after 48 hours on treatment at home, the
child should be reviewed by a pediatric specialist.
B. Children who have hypoxemia or respiratory distress
should receive oxygen therapy.
C. Intravenous fluids, if necessary, may be given at
80% maintenance level with monitoring of serum
electrolytes.
Children with CAP may be cared at home, especially
for those caused by atypical pathogens. As listed in II-
A, several clinical manifestations are predictive for asevere bacteria pneumonia that should be cared in
hospitals. Oral intake usually decreases in children
with pneumonia. If there are obvious signs of dehydration,
the child should also be hospitalized. CAP in neonates
and children with immunodeficiency are prone to being
more severe. Therefore, they should be treated more
aggressively in the hospital.
Hypoxemia and respiratory distress are important risk
factors of a severe disease.44 Oxygen therapy given by
nasal cannula, head box, face mask, or oxygen tent
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should be given to children with hypoxemia, especially
for those with oxygen saturation 92%.18 If blood
oxygenation is not improved after oxygen therapy, patient
should be cared for at an intensive care unit with positive-
pressure respiratory support, such as intubation and use
of ventilator.
V. ANTIBIOTIC THERAPY
A. Principle
1.Empiric use of antibiotics should take into
consideration the age and the disease severity of
the patients. Appropriate antibiotics should be given
as soon as possible after registration for hospitalized
patients.
2. Parenteral antibiotics should be given to children
with severe pneumonia.3. If fever or some grave clinical manifestations persist
beyond 48 hours after treatment, the treatment plan
should be re-evaluated and a follow-up chest image
study should be considered.
4. Oral switch of antibiotics: If the clinical condition
improves rapidly with all of the following
characteristics suggestive of a stabilized illness,
intravenous antibiotics may be considered to be
switched to oral ones.
a. Absence of septic signs, empyema, necrotizing
pneumonia and lung abscess.
b. Stabil ized vital signs for at least 48 hours,
including body temperature, heart rate,
respiratory rate, and blood pressure.
c. No growth on blood culture.
d. May be fed orally.
5. Duration of antibiotic treatment
a. Mycoplasma pneumonia and chlamydia
pneumonia may be treated by appropriate oral
antibiotics for 10 days. If azithromycin is used,
the treatment should be continued for only 3-
5 days.
b. Legionnaires' disease: For immunocompetent
children, azithromycin may be used for 5-10 days,
and other macrolides and fluoroquinolones may
be used for 10-14 days. For immunocompromised
children, macrolides plus fluoroquinolones or
rifampin may be used for 14-21 days.
c. Antibiotics should be given according to the
treatment response, and are usually used for at
least 7-10 days.d. Duration of antibiotic therapy may need to be
prolonged in complicated infections, such as
those complicated by bacteremia or meningitis,
Pseudomonas aeruginosainfection, empyema,
necrotizing pneumonia, and lung abscess.
B. Choice of antibiotics when the pathogen is known:
Current antibiotic-resistance rate of some important
respiratory pathogens in Taiwan include 70% of
penicillin-nonsusceptible S. pneumoniae(minimum
inhibitory concentration 0.12 g/mL), about 60%
of -lactamase-producingH. influenzae, and 50-
70% of community-acquired methicillin-resistantS.
aureus.
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D. Choice of antibiotics under special circumstances:
1. Broad-spectrum and potent antibiotics should be
used in children with sepsis, meningitis, or
complications that may endanger the life.
2. For children with disorders such as bronchiectasis,
chronic lung disease, and severe neuromuscular
disorders and have a history of recurrent pneumonia,
repetitive use of antibiotics, or prolonged use of
steroids, enteric gram-negative bacteria, including
P. aeruginosa, are more likely to be the offending
path oge n. Em pi ri c th era py ma y inc lu de
antipseudomonal -lactams with or without
aminoglycosides.
3. When S. aureus infection is a concern, such as
chest trauma or influenza-associated pneumonia,
antibiotics effective against methicillin-resistant S.
aureusmay be added to the empiric therapy.
E. Recommended dosage of empirical antibiotics (for
children older than 1 month of age):
1. Penicillin: 300,000-400,000 units/kg/day, q4-6h.
2. Ampicillin: 150-200 mg/kg/day, q6h.
3. Amoxicillin: 80-90 mg/kg/day, po tid.
4. Oxacillin: 100-300 mg/kg/day, q4-6h.
5. Ampicillin/sulbactam: 150-200 ampicillin mg/kg/
day, q6-8h.
6. Amoxicillin/clavulanate: 150-200 amoxicillin mg/
kg/day, iv q6-8h; 80-90 amoxicillin mg/kg/day,
po bid-tid.
7. Cefazolin: 50-100 mg/kg/daym, iv q8-6hv.
8. Cefuroxime: 100-200 mg/kg/day, iv q6-8h; 20-
30 mg/kg/day, po bid, may double the dose for
severe infection.
9. Ticarcillin/clavulanate: 200-300 ticarcillin mg/kg/
day, q6-8h.
10. Piperacillin/tazobactam: 200-300 piperacillin mg/
kg/day, q6-8h.
11. Cefotaxime: 150-200 mg/kg/day, q6h.
12. Ceftriaxone: 100 mg/kg/day, q12h - qd.
13. Ceftazidime: 100-150 mg/kg/day, q6-8h.
14. Cefepime: 100-150 mg/kg/day, q8-12h.
15. Imipenem: 60-100 mg/kg/day, q6h.
16. Meropenem: 60-100 mg/kg/day, q6-8h.
17. Erytrhomycin: 40 mg/kg/day, q6h.
18. Clarithromycin: 15 mg/kg/day, q12h.
19. Azithromycin: 10-12 mg/kg/day, qd.
20. Tetracycline: 25-50 mg/kg/day, po bid-qid.
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21. Minocycline: 4 mg/kg loading, then 2 mg/kg po
q12h.
22. Doxycycline: 4.4 mg/kg/day loading, then 2.2-
4.4 mg/kg po qd.
23. Vancomycin: 20-60 mg/kg/day, q6-8h.
24. Teicoplanin: 10 mg/kg q12h loading doses for 3
doses, then 10-20 mg/kg, qd.
25. Linezolid: 20-30 mg/kg/day, q8-12h.
26. Rifampin: 10-15 mg/kg/day, qd.
27. Gentamicin: 6-7.5 mg/kg/day, bid-qd.
28. Tobramycin: 6-7.5 mg/kg/day, bid-qd.
29. Netilmicin: 5.5-8.0 mg/kg/day, bid-qd.
30. Amikacin: 15-25 mg/kg/day, bid-qd.
31. Ciprofloxacin: 20-40 mg/kg/day, q12h.
Age and disease severity are the two most important
factors in deciding whether antibiotics should be used
or which antibiotics should be chosen. For example,viral infections are more prevalent in young children,4and it is recommended that young children presenting
with mild symptoms of lower respiratory tract infection
need not be treated with antibiotics.18Studies showed
that initiation of antibiotics within 4 to 8 hours after arrival
at hospital correlated strongly with the outcome.45,46
Appropriate antibiotics should be given as soon as possible
after registration for hospitalized patients.
Orally administered antibiotics are safe and effective
for children with community-acquired pneumonia that
is not associated with clinical manifestations suggestive
of a grave illness. Parenteral antibiotics can ensure a
rapidly rising high serum concentration and should begiven to children with clinical manifestations suggestive
of a severe pneumonia and to those who cannot be fed
orally.
Some viral pneumonia may have a prolonged fever,
and some bacterial pneumonia may have a persistent fever
after using appropriate antibiotics, especially for those
with consolidation and pleural effusion.6 However,
clinical conditions of bacteria pneumonia that are
responsive to antibiotics usually improved within 48 hours
after treatment with defervescence.6If fever or some
grave clinical manifestations persist beyond 48 hours
after treatment, the treatment plan should be re-evaluated
and a follow-up chest image study should be considered.There have been limited data published regarding
intravenous-to-oral sequential antibiotic therapy in Taiwan.47Some randomized studies suggested that intravenous-
to-oral switch of antibiotics may be feasible for some
clinically stable and antibiotic-responsive CAP.32Such
a practice may be able to reduce the cost of treatment
and the length of stay in the hospital. We recommend
that oral switch of antibiotics may be applied to CAP
in children without evidence of sepsis, empyema,
necrotizing pneumonia, and lung abscess when the
vital signs have been stabilized for at least 48 hours
and when the patient can be fed orally. Generally, the
antibiotic switch can take place after 2-4 days of
intravenous therapy.32
There is no appropriate randomized study to define
the optimal duration of antibiotic therapy for CAP. Most
recommendations are conjectural, and many physicians
recommend treatment for 1-2 weeks.32The recommended
durations of treatment in this guideline are based on the
experiences of experts and some statements in textbooks.
Seven to 10 days of treatment is usually enough with
2 exceptions. One is Legionnaires' disease that may
be more severe than other causes of atypical pneumonia,
especially when it occurs in immunocompromised children.
The recommended duration is longer. The other is
complicated pneumonia that may require a longer duration
of treatment, including those complicated by bacteremia
or meningitis, Pseudomonas aeruginosa infection,empyema, necrotizing pneumonia, and lung abscess.
Community-acquired P. aeruginosa sepsis with or
without pneumonia is most frequently seen in infants.48One study showed that 8-day therapy forP. aeruginosa
pneumonia led to relapse more commonly than did 15-
day therapy.49
When the pathogen is known, the antibiotic should
be chosen according to the antibiotic susceptibility pattern.
Antibiotic resistance among pneumococci is increasing
and the incidence of severe pneumococcal pneumonia
is apparently increasing in recent years.50Being the same
as our previous version of guideline,51 a penicillin
minimum inhibitory concentration (MIC) of < 1 g/mLwas defined as penicillin susceptible, MIC 4 g/mL
as penicillin resistant, and an intermediate MIC as
penicillin intermediate. Recently, penicillin MIC's
of about 70% of S. pneumoniae strains in Taiwan
are 0.12 g/mL, while only less than 5% is penicillin-
resistant (MIC 4 g/mL).52Therefore, most penicillin-
nonsusceptible S. pneumoniaeinfection can be treated
by a high dose of penicillin and its analogue. On the
other hand, erythromycin resistance in S. pneumoniae
has remained high (94%) in Taiwan in recent years.52
Likewise, trimethoprim-sulfamethoxazole resistance rate
is also high (65%).53
Recent studies in Taiwan showed that 56% of H.influenzaeisolates produce -lactamase, as did nearly
all Moraxella catarrhalis isolates (95.7%). Only
1.7% ofH. influenzaewere -lactamase negative and
amoxicillin resistant.53Antibiotics used for these gram-
negative bacteria should be stable to -lactamase. The
resistance rate to trimethoprim-sulfamethoxazole is 52%
for H. influenzae.53
Having being a predominant pathogen in nosocomial
infections in Taiwan for many years, methicillin-resistance
S. aureusis now becoming more and more common
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in community-acquired infections. Recent data
demonstrated that 50-70% of community strains of S.
aureusobtained from pediatric patients is resistant to
methicillin.12,13 Vancomycin and other agents active
against methicillin-resistance S. aureus may be considered
in selected cases, especially for those with chest trauma
and influenza.54
M. pneumoniae, C. pneumoniaeand C. trachomatis
are rarely resistant to erythromycin and other macrolides
that should be the drug of choice for these infections.
Different macrolides have similar therapeutic efficacy.6Tetracyclines may be used as an alternative only when
the child is older than 8 years to avoid their potential
detrimental effects on bone and teeth. Although
fluoroquinolones may be used as the first-line drug for
treatingL. pneumophila infection,32,55new macrolides
are a more preferred agent in children. Rifampin or
fluoroquinolones may be added in severe infections.When the pathogen is unknown, either before the
culture result is available or due to a negative result of
microbiological test, antibiotics may be given empirically
based on the knowledge of predominant pathogens in
each age groups.
For neonates younger than 1 month, Escherichia
coli, group B streptococcus and other bacteria are
common pathogens. They may be treated empirically
by ampicillin + aminoglycosides, or by ampicillin +
cefotaxime or ceftriaxone when meningitis is a concern.
Common bacterial pathogens of CAP in children between
2 months and 5 years of age include S. pneumoniae
andH. influenzaetype b. -lactams stable to -lactamasemay be used empirically. S. pneumoniaebecomes the
single most important etiology of CAP in children beyond
6 years of age. Penicillin may be used as empirical therapy
for clinically stable patients.
M. pneumoniaeand C. pneumoniae infections are
not infrequent after 2 years of age.6,7For children older
than 2 years with suspected atypical pneumonia,
macrolides are the antibiotic of choice. However, such
infections are not totally absent in children younger than
2 years,6and C. trachomatisis a possible etiology of
CAP in infants.8Macrolide antibiotics may be used in
special circumstances.
The choice of antibiotics should also take into accountthe severity of illness and comorbidities. Several
guidelines for management of CAP in adults stratify
patients into groups based on site of therapy (i.e.
outpatient, inpatient, or intensive care unit),
comorbidities (including cardiopulmonary disease,
diabetes mellitus, renal failure, malignancy), and risk
factors for infection with drug-resistant bacteria.32,55,56
To avoid too many stratifications, the working group
choose to stratify pediatric patients by the age only.
However, some points deserve further attention.
A few retrospective studies suggested that dual
therapy with -lactams and a macrolide may reduce
mortality associated with bacteremic pneumococcus
pneumonia. 57,58 Two possible explanations are the
immunonodulating effect of macrolides and a concomitant
infection by atypical pathogens that may be susceptible
to macrolides. A well-designed prospective study is
needed to prove such an observation, and the data in
pediatric patients are still lacking. However, adding
a macrolide for children with suspected pyogenic
pneumonia may be warranted since mixed infections are
not uncommon in children with CAP.
With life-threatening complications, such as sepsis
and meningitis, CAP in children may be treated
empirically with broad-spectrum and potent antibiotics,
such as vancomycin plus a third-generation cephalosporin
or other antibiotics effective against commonly seen gram-
negative bacteria.Enteric gram-negative bacteria, such asP. aeruginosa,
may pose some impact on selection of an appropriate
antibiotic for treatment of CAP. Several risk factors have
been recognized in adult patients.56Patients who reside
in a nursing home, or have underlying cardiopulmonary
disease or multiple comorbidities, or have received recent
antimicrobial therapy are more likely to be infected by
enteric organisms. Risk factors for P. aeruginosa
infection include structural lung disease (e.g.
bronchiectasis), steroid therapy, recent use of broad-
spectrum antibiotic, and malnutrition. Although similar
data are lacking for children, the working group makes
similar recommendations. When children with disorderssuch as bronchiectasis, chronic lung disease, and severe
neuromuscular disorders have a history of recurrent
pneumonia, repetitive use of antibiotics, or prolonged
use of steroids, they tended to be infected by gram-
negative bacteria, including P. aeruginosa. Empiric
therapy may include antipseudomonal -lactams
(including ceftazidime, piperacillin, ticarcillin/clavulanate,
piperacillin/tazobactam, cefepime, imipenem, and
meropenem) with or without aminoglycosides.
Because some antibiotic-resistant bacteria, especially
penicillin-nonsusceptible S. pneumoniae, are highly
prevalent in Taiwan, the dosage of some antibiotics should
be modified. As mentioned before, less than 5% ofpenicillin-nonsusceptible S. pneumoniae is truly resistant
to penic il lin with a MIC 4 g/mL in Taiwan,52
increasing the dose of penicillin, ampicillin, amoxicillin,
ampicillin/sulbactam, amoxicillin/clavulanate, cefuroxime,
and cefotaxime may be an effective way to treat infections
caused by penicillin-intermediate S. pneumoniae. The
recommended dosage of various antibiotics in present
guideline is for empirical use of antibiotics. The dosage
of antibiotics may be adjusted when the pathogen and
its antibiotic susceptibility pattern are known. For
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Community-acquired pneumonia Vol. 48, No. 4, 2007176
example, when dealing with penicillin-susceptible S.
pneumoniae infection, the dose of penicillin may be
lowered down.
As suggested by recent pharmacokinetic and
pharmacodynamic studies, some antibiotics are time-
dependent for their therapeutic effect, including -lactams
and macrolides. Frequent dosing may improve their
performance. On the other hand, Some antibiotics are
concentration-dependent, including aminoglycosides and
fluoroquinolones. Such antibiotics should be given with
a longer dosing interval to maximize their therapeutic
effect.59In the era of increasing resistance, an dosing
schedule with optimized pharmacokinetic and
pharmacodynamic features can not only bring about a
better treatment response, but also prevent the emergence
of resistant bacteria. The recommended dosage in this
guideline was set up according to this principle.
VI. POST-TREATMENT EVALUATION AND
MANAGEMENT OF COMPLICATION
A. If the fever persists, the clinical condition is not
improved, or aggravating signs appeared after
treatment, the following conditions should be
considered.
1. Inadequate dose of antibiotics.
2. Antimicrobials not effective for offending pathogen,
such as antibiotic-resistant bacteria, tuberculosis.
3. Viral infection or mixed infection.
4. Extrapulmonary focus of infection.5. Complication of pneumonia, such as lung abscess,
empyema.
6. Drug fever.
B. Complication of pneumonia:
1. Pleural effusion, empyema.
2. Necrotizing pneumonia, lung abscess.
3. Acute respiratory distress syndrome.
4. Others, such as bronchopleural fistula.
C. Management of pleural effusion and empyema:
1. Diagnosis: lateral decubitus chest radiography or
chest ultrasonography. The latter is preferred.
2. Pleural tapping: Examinations of pleural fluid should
include white count and differentials, pH value,glucose, protein, gram stain, acid-fast stain,
bacterial culture, mycobacteria culture. Bacteria
antigen detection may also be considered.
3. With one of the following conditions, drainage
of pleural fluid should be required:
a. Pus-like effusion.
b. Positive finding of gram stain or bacterial culture
of pleural fluid.
c. Large amount of fibrinous substances or septations
in pleural cavity.
d. Massive pleural effusion associated with
respiratory distress.
e. pH of pleural fluid < 7.2.
4. Draining procedure
a. Simple chest tube drainage: not recommended.
b. Chest tube drainage with firbrinolytic agents: Use
streptokinase 2,500 U/mL or urokinae 1,000 U/
mL with a dose of 3-4 mL/kg that does not exceed
100 mL. The agent may be given once per day
with retention of the agent for 2-4 hours each
time. The therapy may be instituted for 2-3 days
or until there is a significant improvement of chest
images. Tissue plasminogen activator may be
used with a dose of 2-5 gm in 50-250 mL saline.
c. Video-assisted thoracoscopic surgery (VATS):
Computerized tomography of the chest should
be per formed previous to this procedure to
delineate the extent of pleural effusion. EarlyVATS that is performed within 4 days after the
diagnosis is more effective than late VATS.
d. If the above mentioned draining procedures fail
to improve the condition, such as persistent high
fever and severe respiratory distress, open surgery
for drainage may be considered.
D. Management of necrotizing pneumonia and lung
abscess: Chest ultrasonography or computerized
tomography should be performed. If the clinical
condition does not improve after appropriate
antimicrobial therapy and drainage, open surgery may
be considered.
If the fever persists, the clinical condition is not
improved or even aggravated after treatment, several
possibilities should be considered.60Because penicillin-
nonsusceptible S. pneumoniae is highly prevalent in
Taiwan,50,52an adequate dose of antibiotics as mentioned
in present guideline is a prerequisite to ensure treatment
success. For young infants and children with risk factors,
antibiotics with a broader antibacterial spectrum may be
necessary to be effective against potential pathogens,
including methicillin-resistant S. aureus10,11and enteric
gram-negative bacteria.56As mentioned previously, M.
tuberculosisinfection is prevalent in Taiwan and should
be regarded as a possible etiology in CAP unresponsiveto empiric antibiotic therapy.15
Viral infection and extrapulmonary focus of infection
are also possible causes for an unresponsive CAP. A
study in Taiwan showed that children with a severe
pneumonic change (consolidation or pleural effusion)
or extrapulmonary manifestations (e.g. encephalitis,
hepatitis) tended to have a prolonged fever after
appropriate macrolide treatment in children with either
M. pneumoniaeor C. pneumoniaeinfection.6Adequate
drainage of lung abscess and empyema may be necessary
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for some complicated pneumonia.
Drug fever is easily overlooked because affected
patients may have an extremely high temperature and
a high CRP value. Sulfonamides and -lactams are
common causes of drug fever. However, it should be
assumed that any drug can cause drug fever, including
nonantibiotics.60Fever may developed a few days after
using an antibiotic.61A relatively good activity with
re-emergence of fever after defervescence for some days
after treatment is characteristic for drug fever. Other
helpful clues to drug fever are skin rashes, relative
bradycardia , neutropenia, eos inophilia, atypical
lymphocytosis, elevations of the serum transaminases.61,62The diagnosis of drug fever may be confirmed by
observing a subsidence of fever after withholding the
offending medication. Drug fever usually subsides within
72 hours after the sensitizing drug is discontinued if a
rash is not present.
61
Parapneumonic pleural effusion is not uncommon
in children with bacterial pneumonia and is a common
cause of prolonged fever after treatment. A study in
Taiwan showed that 56% of pneumococcus pneumonia
in children is complicated.50It has been recommended
that for all adult patients with acute bacterial pneumonia,
the presence of a parapneumonic effusion should be
considered.63The effusion may be delineated by lateral
decubitus chest radiography or by chest ultrasonography.
Chest ultrasonography is preferred because it is more
accurate relative to lateral decubitus chest radiography
for the diagnosis of small pleural effusions.64
Aspirated pleural fluid should be sent for necessarytests. Some studies showed that commercially available
pneumococcal antigen test that was designed for
cerebrospinal fluid samples may also be useful for pleural
fluid.65,66Although available data are limited, the working
group suggests that such a bacteria antigen test may be
used for pleural fluid when S. pneumoniae infection
is one of the possible pathogen.
It is a common agreement that a frankly purulent
effusion or an effusion containing bacteria as evidenced
by either culture or gram stain should be drained to hasten
the recovery and to avoid complications. Dilemma occurs
when the effusion does not appear purulent. A meta-
analysis suggested that a low pH < 7.21-
7.29 was the
most accurate predictor of the need for drainage.67The
cut-off point for pH is controvers ial. The present
recommendation adopts a pH of 7.2 as a cut-off, similar
to that recommended by the American College of Chest
Physicians.63
There are several drainage procedures. A recent
review showed that the pooled mortality was higher for
the no drainage (6.6%), therapeutic thoracentesis (10.
3%), and tube thoracostomy (8.8%) than for the
fibrinolytic (4.3%), VATS (4.8%), and surgery (1.9%).
The pooled proportion of patients needing a second
intervention was also higher for the no drainage,
therapeutic thoracentesis, and tube thoracostomy
management approaches.63
Adding streptokinase, urokinase or tissue plasminogen
activator into the chest cavity may facilitate the drainage
by causing lysis of fibrins and septations. Fibrinolytic
agents are resolved in normal saline that is instituted into
a properly positioned chest tube. The drainage is held
for several hours for firbrinolytic agents to take effect.
Several studies in Taiwan have shown that intrapleural
fibrinolytic treatment is safe and effective in children,
and it can obviate the need for surgery.68,69There is not
a consensus on the dosage of firbrinolytic agents.
However, the working group suggests one dosage
schedule according to the experience in Taiwan.
Most studies agree that debridement of the pleuralspace by VATS is effective for the management of pleural
empyema, including studies in children. Data also
suggested that the main prognostic factor for thoracoscopic
treatment of pleural empyema is the interval between
diagnosis and surgery.70,71A 4-day limit, corresponding
to the natural process of empyema organization, may
significantly affect the efficacy of VATS.70,72Therefore,
VATS should be attempted within 4 days after diagnosis
when necessary. Open surgery is another option for the
treatment of pleural empyema in children.
Necrotizing pneumonia and lung abscess are not
uncommon in children with CAP. Diagnosis may be
confirmed by ultrasonography or computerizedtomography. Prolonged antibiotic therapy may be required.
Infrequently, open surgery may be needed in complicated
cases refractory to medical therapy.
VII. PREVENTION
A. General principles: reduce the risk of exposure to
respiratory pathogens by droplet precautions.
B. Immunization:
1. Bacille Calmette-Gurin vaccine: routine for all
neonates and 7-year-old children who has a negative
tuberculin reaction.2. Influenza vaccine:
a. Routine for children aged 6-23 months.
b. Recommended for children older than 23 months
with high-risk conditions.
3. Pneumococcal vaccine: 23-valent pneumococcal
polysaccharide vaccine (PPV23) for children older
than 2 years and 7-valent pneumococcal conjugate
vaccine (PCV7) for children older than 2 months.
Recommended schedule for those having not
received pneumococcal vaccines:
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Community-acquired pneumonia Vol. 48, No. 4, 2007178
C. Preventive therapy:
1. Tuberculosis: isoniazid 10 mg/kg/day (maximum
300 mg/day) for 9 months recommended for children
12 years with evidence of latent tuberculosis
infection and a history of close contact with patients
with infectious tuberculosis.
2.Haemophilus influenzaetype b infection: rifampin
20 mg/kg (maximum 600 mg) daily for 4 days for
all household contacts when at least 1 contact is
younger than 4 years of age.
Pathogens responsible for CAP are transmitted by
droplet, while most bacterial pneumonia may be
complications of some preceding virus infection.73
Preventive measures for CAP include droplet precautions
for hospitalized children, strict hand hygiene procedures,
and that infected children should be excluded from school
and day care facilities until they are no longer considered
contagious.
According to the guidelines for the diagnosis andtreatment of tuberculosis in Taiwan, one dose of BCG
should be given to all neonates with a body weight
2,500 gm. Tuberculin skin test is done at school entry
(7 years of age) for children whose BCG scar is 2 mm
in diameter. One dose of BCG should be given to those
who have a negative tuberculin reaction.
Currently, influenza vaccine is a routine for children
aged between 6 and 23 months in Taiwan. The vaccine
is also recommended for children older than 23 months
of age with risk factors, including chronic pulmonary
diseases (e.g. bronchopulmonary dysplasia, cystic
fibrosis, bronchiolitis obliterans, laryngotracheomalasia,
asthma), hemodynamically significant cardiac disease,immunosuppresive disorders or therapy, human
immunodeficiency virus infection, hemoglobinopathies,
disorders requiring long term salicylate therapy (e.g.
rheumatoid arthritis, Kawasaki disease), chronic renal
dysfunction, chronic metabolic disease (including diabetes
mellitus), and any condition that can compromise
respiratory function or handling of respiratory tract
secretions or that can increase the risk of aspiration.74
Two pneumococcal vaccines are available in Taiwan,
including a 23-valent polysaccharide pneumococcal
vaccine (PPV23) for use in children aged over 2 year,
and a 7-valent pneumococcal conjugate vaccine (PCV7)
for children between 2 months and 9 years of age. The
PCV7 is recommended for routine vaccination at 2, 4,
6, and 12-18 months of age. Catch-up vaccination is
also recommended for children up to 23 months of age
with fewer doses of PCV7. The cost-effectiveness of
pneumococcal vaccines in healthy children between 24
and 59 months of age remain to be studied. Pneumococcal
vaccines may be given to all children older than 24
months of age with risk factors, including
hemoglobinopathies, congenital or acquired immune
deficiency, human immunodeficiency virus infection,
chronic pulmonary disease, chronic renal disorders,
diabetes mellitus, anatomical abnormalities associated
with higher rates or severity, cerebrospinal leaks,
hemodynamically significant heart disease, and chronic
pulmonary disease.75
Recent revision of the guidelines for the diagnosisand treatment of tuberculosis in Taiwan recommends that
isoniazid chemoprophylaxis may be given to children
12 years with evidence of latent tuberculosis infection
by the tuberculin reaction and a history of close contact
with patients with infectious tuberculosis. The risk of
invasive Haemophilus inf luenzae type b disease is
increased among household contacts who are less than
4 years of age. Rifampin 20 mg/kg (maximum 600 mg)
daily for 4 days is recommended for all household
contacts in such occasions regardless of the age of
household contacts and theHaemophilus influenzaetype
b vaccination history.
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