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Recent Patents on Inflammation & Allergy Drug Discovery 2018, 12, 136-144
REVIEW ARTICLE
ISSN: 1872-213X
eISSN: 2212-2710

Inflammation
& Allergy
Drug Discovery

Community-Acquired Pneumonia in Children

Alexander K.C. Leung1,*, Alex H.C. Wong2 and Kam L. Hon3

1
Recent Patents on Inflammation &Allergy Drug Discovery

Department of Pediatrics, The University of Calgary, Alberta Children’s Hospital, Calgary, Alberta, Canada;
2
Department of Family Medicine, The University of Calgary, Calgary, Alberta, Canada; 3Department of Paediatrics,
The Chinese University of Hong Kong, Shatin, Hong Kong

Abstract: Background: Community-acquired pneumonia is an important cause of morbidity in devel-

ARTICLE HISTORY
Received: February 22, 2018
Revised: June 21, 2018
Accepted: June 21, 2018
DOI:
10.2174/1872213X12666180621163821
Keywords: Amoxicillin, chest infection, cough, fever, respiratory syncytial virus, Streptococcus pneumoniae, tachypnea.
oped countries and an important cause of morbidity and mortality in developing countries. Prompt di-
agnosis and appropriate treatment are very important.
Objective: To provide an update on the evaluation, diagnosis, and treatment of community-acquired
pneumonia in children.
Methods: A PubMed search was completed in Clinical Queries using the key term “community-
acquired pneumonia”. The search strategy included meta-analyses, randomized controlled trials,
clinical trials, observational studies, and reviews. Patents were searched using the key term
“community-acquired pneumonia” from www.google.com/patents, http://espacenet.com, and www.
freepatentsonline.com.
Results: Generally, viruses, notably respiratory syncytial virus, are the most common cause of commu-
nity-acquired pneumonia in children younger than 5 years. Streptococcus pneumoniae is the most
common bacterial cause across all age groups. Other important bacterial causes in children younger
than 5 years include Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and
Moraxella catarrhalis. In children 5 years or older, in addition to S. pneumoniae, other important bacte-
rial causes include Mycoplasma pneumoniae and Chlamydophila pneumonia. In the majority of cases,
bacterial and viral pneumonia cannot be reliably distinguished from each other on clinical grounds. In
practice, most children with pneumonia are treated empirically with antibiotics; the choice of which
depends on the patient’s age and most likely pathogen. Recent patents related to the management of
community-acquired pneumonia are discussed.
Conclusion: In previously healthy children under the age of 5 years, high dose amoxicillin is the treat-
ment of choice. For those with type 1 hypersensitivity to penicillin, clindamycin, azithromycin,
clarithromycin, and levofloxacin are reasonable alternatives. For children with a non-type 1 hypersensi-
tivity to penicillin, cephalosporins such as cefixime, cefprozil, cefdinir, cefpodoxime, and cefuroxime
should be considered. In previously healthy children over the age of 5 years, macrolides such as
azithromycin and clarithromycin are the drugs of choice.

1. INTRODUCTION Organization (WHO) estimates that approximately 2 million

children under the age of 5 years die of pneumonia each year
Community-acquired pneumonia in childhood is defined
worldwide; the majority of these deaths occur in developing
as an acute infection of the pulmonary parenchyma in a child
countries [4, 5]. The mortality rate in developed countries is
caused by a pathogen acquired outside the hospital, that is, in
less than 1 per 1000 per year [1, 3]. Nevertheless, commu-
the community [1, 2]. It is an important cause of morbidity in
nity-acquired pneumonia is associated with enormous costs
developed countries and an important cause of morbidity and either directly through medical expenses or indirectly
mortality in developing countries [3]. The World Health
through loss of working hours by parents of sick children
[6].
*Address correspondence to this author at The University of Calgary, Al-
berta Children’s Hospital, #200, 233 – 16th Avenue NW, Calgary, Alberta, 2. ETIOLOGY
Canada T2M 0H5; Tel: (403) 230 3300; Fax: (403) 230 3322;
E-mail: aleung@ucalgary.ca
The causative agents vary according to the age of the
child and, to a lesser extent, the setting in which the infection

2212-2710/18 $58.00+.00 © 2018 Bentham Science Publishers

Community-Acquired Pneumonia Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2 137
is acquired [1]. Generally, viruses are the most common
cause of community-acquired pneumonia in children
younger than 5 years; the incidence of which decreases with
increasing age [7-11]. Viruses alone account for up to 50%
of cases in young children [1, 3]. As viral infections that
have damaged mucosal linings of respiratory tracts may lead
to secondary bacterial infections, coinfection with bacteria
has been reported in up to 33% of cases [12-14].
The respiratory syncytial virus is the most common viral
cause of community-acquired pneumonia especially in
young children [15-19]. Other viral pathogens include
parainfluenza viruses 1, 2, and 3, influenza A and B viruses,
adenovirus, rhinovirus, human metapneumovirus, human
bocavirus, parechovirus, coronaviruses, and enterovirus [1,
8, 10, 17-19].
Streptococcus pneumoniae is the most common bacterial
cause across all age groups [3, 7, 9, 17, 20-23]. This pattern
may change with the advent of universal childhood immuni-
zation with pneumococcal vaccine. Other important bacterial
causes in children younger than 5 years include Haemophilus
influenzae (nontypable and typeable), Streptococcus
pyogenes, Staphylococcus aureus, Moraxella catarrhalis,
and Mycoplasma pneumoniae [1, 9, 21]. Afebrile pneumonia
of infancy is usually caused by Chlamydia trachomatis but
Mycoplasma hominis and Ureaplasma urealyticum have also
been implicated [1]. Bordetella pertussis should be consid-
ered in the young and unimmunized child with paroxysmal
cough, inspiratory whoop, and posttussive vomiting [24, 25].
In children 5 years or older, in addition to S. pneumoniae,
other important bacterial causes include Mycoplasma pneu-
moniae and Chlamydophila pneumonia (previously known
as Chlamydia pneumonia) [10, 26]. When there is a history
of aspiration, pneumonia is usually caused by anaerobic oral
flora such as anaerobic streptococci, Bacteroides species,
Fusobacterium species, and Prevotella melaninogenica [1].
In cystic fibrosis, S. aureus, Pseudomonas aeruginosa,
nontypable H. influenzae, Burkholderia cepacia, and other
gram-negative rods are encountered with increasing fre-
quency [1]. In immunodeficient children, pathogens such as
Mycobacterium tuberculosis, atypical mycobacteria, Pneu-
mocystis jiroveci (previously known as P. carinii), Es-
cherichia coli, Salmonella species, Aspergillus species, and
Fusarium species should be considered in addition to the
usual bacterial pathogens that infect immunocompetent chil-
dren [1, 10]. Tuberculosis should be considered if the patient
has recently travelled to an endemic area and/or has had con-
tact with an individual with active tuberculosis [24].
3. EPIDEMIOLOGY
Community-acquired pneumonia is common in the de-
veloping world, estimated at 0.28 episodes per child per year
[16, 22, 27]. In developed countries, the annual incidence of
community-acquired pneumonia is 36 to 40 per 1,000 chil-
dren younger than 5 years of age and 11 to 16 per 1,000
children 5 to 14 years of age [14, 28, 29]. In North America,
the annual incidence is 30 to 45 per 1,000 children younger
than 5 years of age and 6 to 12 per 1,000 children older than
9 years of age [10]. In the UK, the incidence of children ad-
mitted to hospital between 2001 and 2002 (the
prepneumococcal vaccine era) was 33.8 per 10,000 children
younger than 5 years of age and 14.4 per 10,000 children 15
years and under [30]. Admission rates for community-
acquired pneumonia in the UK decreased by 19% between
2006 and 2008 following the introduction of conjugate
pneumococcal vaccine (PCV7) to the national childhood
immunization programme [31]. In the USA, the hospital ad-
mission rates for community-acquired pneumonia have de-
creased by approximately 30 to 40% after pneumococcal
vaccination became universal [24, 32, 33]. The incidence is
slightly higher in boys than in girls [6, 22, 34]. Community-
acquired pneumonia is more prevalent in the fall and winter
[35, 36]. Prematurity, malnutrition, low socioeconomic fam-
ily status, crowded living conditions, daycare attendance,
influenza infection, recurrent respiratory infections, chronic
respiratory disease (e.g., cystic fibrosis, bronchopulmonary
dysplasia, asthma), congenital heart disease, neuromuscular
disorder, immunodeficiency, tobacco exposure, alco-
hol/substances abuse, and lack of access to medical care are
other risk factors [7, 12, 22, 34, 37, 38]. On the other hand,
immunization with H. influenzae type b (Hib), influenza, and
pneumococcal vaccines have a protective effect [39].
4. PATHOGENESIS
Pneumonia develops when the normal defensive mecha-
nisms (mechanical and anatomic barriers, mucociliary clear-
ance of secretions, clearing of the airway by cough, phago-
cytic activity, humoral immunity, and cell-mediated immu-
nity) in the lower respiratory tract are impaired and invaded
or overwhelmed by a pathogen [15]. With impaired clear-
ance of the pathogen in the lower respiratory tract, the
proliferation of the pathogen in the lower respiratory tract
triggers an immune and inflammatory process with resultant
accumulation of fluid, white blood cells, cellular debris in
the alveoli [1, 15]. This leads to a reduction in pulmonary
compliance, increase in pulmonary resistance, collapse of
alveoli, and pulmonary ventilation-perfusion mismatch, giv-
ing rise to the symptoms and signs of pneumonia [1, 15].
5. CLINICAL MANIFESTATIONS
The clinical manifestations vary depending on the age
and health of the child, the responsible pathogen, and sever-
ity of the illness. The clinical features are nonspecific in that
no single symptom or sign is pathognomonic for pneumonia
[3, 40]. Common symptoms include fever, cough, and
difficulty in breathing [22, 39, 40]. Children without fever,
cough, or symptoms of respiratory distress are unlikely to
have pneumonia [6]. However, infants may simply present
with poor feeding, lethargy, irritability, restlessness, and
inconsolable crying [3, 40]. Some older children may com-
plain of pleuritic chest pain, abdominal pain (referred pain
from the lower lobe), neck pain or stiff neck (referred pain
from the upper lobe) [24, 35, 39, 40].
Important physical findings include fever, tachypnea,
wheezing, cyanosis, nasal flaring, grunting, use of accessory
muscles, intercostal/subcostal/suprasternal retractions, rhon-
chi, crackles (rales, crepitations), decreased breath sounds
(parenchymal consolidation), bronchial breath sounds (par-
enchymal consolidation), egophony (e to a change), bron-
chophony (distant transmission of sounds), whispered pecto-
riloquy, tactile fremitus (parenchymal consolidation), and
138 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2
dullness to percussion (parenchymal consolidation) [3, 11,
40]. Tachypnea seems to be the most significant sign [10,
11]. The World Health Organization (WHO) uses tachypnea
(defined as  50 breaths/min in infants 2 to 12 months of
age,  40 breaths/min in children 1 to 5 years of age, and 
20 breaths/min in children 5 years of age and older) in the
presence of cough as the diagnostic criterion of pneumonia
in developing countries where access to chest radiography is
limited [11]. It should be noted that the respiratory rate may
go up by as many as 10 breaths per minute per degree in-
crease in Celsius in body temperature [3, 11]. In a recent
study of 128 children with community-acquired pneumonia,
only three physical findings, namely, respiratory rate, retrac-
tions, and wheezing had acceptable levels of interrater reli-
ability [41].
High fever (> 38.5ºC), chills and rigors, toxic appear-
ance, marked tachypnea, and localized auscultatory findings
are more in keeping with bacterial pneumonia [15, 39]. On
the other hand, low-grade fever, general well-being, runny
nose, myalgia, wheezing, and diffuse and bilateral ausculta-
tory findings favor viral pneumonia [35, 40]. Wheezing is
more common in pneumonia caused by viruses, M. pneumo-
niae, and C. pneumoniae [10, 24, 40, 42]. Absent breath
sounds with a dull percussion note raise the possibility of
pneumonia complicated by pleural effusion [6]. Extrapul-
monary findings such as erythema multiforme, nonexudative
pharyngitis, myocarditis, arthritis, and hemolytic anemia
suggest pneumonia caused by M. pneumoniae [35].
6. LABORATORY INVESTIGATIONS
Although chest radiograph is generally regarded as the
gold standard for a diagnosis of pneumonia [16, 42, 43],
some authors suggest that routine use of a chest radiograph
for every single child with mild, uncomplicated lower respi-
ratory tract infection might not be appropriate [6, 12, 23, 36].
Other authors, however, recommend that chest radiograph is
necessary to diagnose pneumonia in children [34, 43]. Defi-
nite indications for chest radiographs include confirmation of
diagnosis when clinical findings are inconclusive; exclusion
of pneumonia in young children (< 3 years) with fever >
39ºC and leukocytosis ( 20,000 white blood cells/L) and
in older children (3 to 10 years) years with fever > 38ºC,
leukocytosis ( 15,000 white blood cells/L), and cough;
severe pneumonia with significant respiratory distress (to
assess for complications); prolonged pneumonia; pneumonia
unresponsive to antimicrobial treatment, and recurrent
pneumonia [19, 40, 44]. Certain chest radiographic findings
can suggest a particular etiology. Segmental/lobar consolida-
tion is typically seen with bacterial pneumonia whereas in-
terstitial infiltrates with viral pneumonia and pneumonia
caused by M. pneumoniae [23, 36, 40, 42]. Round or spheri-
cal consolidation is commonly associated with S. pneumo-
niae [15, 23]. Caseating granuloma and hilar lymphadenopa-
thy suggest tuberculosis [12]. Pleural effusion, pneumatoce-
les, cavitation, and necrotizing process are significant predic-
tors of bacterial pneumonia [11, 15].
In recent years, lung ultrasound has become a valuable
tool in the diagnosis of community-acquired pneumonia.
Lung ultrasound is easily accessible, inexpensive, sensitive,
Leung et al.
and radiation-free [45-49]. A positive lung ultrasound may
minimize the need of performing a chest radiograph [45].
Inflammatory markers such as white blood cell count, C-
reactive protein, and erythrocyte sedimentation rate are often
performed to try to distinguish bacterial from viral pneumo-
nia. These inflammatory markers have low sensitivity and
specificity for bacterial pneumonia and need not be routinely
measured in fully immunized children with community-
acquired pneumonia managed as outpatients [2, 6, 19, 40,
42]. Measurements of these inflammatory markers should be
considered for children with serious pneumonia requiring
hospitalization [2, 40]. A white blood cell count >
15,000/mm3 with a predominance of granulocytes and ele-
vated C-reactive protein and erythrocyte sedimentation rate
are suggestive of bacterial pneumonia [40]. Peripheral eosi-
nophilia may be seen in infants with afebrile pneumonia of
infancy typically caused by C. trachomatis [15, 40]. Serum
procalcitonin has better specificity than C-reactive protein
and erythrocyte sedimentation rate for differentiating bacte-
rial from viral pneumonia [12, 42]. High serum procalcitonin
is a good marker for bacterial pneumonia [39, 50]. These
inflammatory markers, if measured longitudinally, may be
used in conjunction with clinical findings to assess response
to antibiotic treatment [2, 9, 35].
Gram stain and culture of sputum is impossible to obtain
in young children. Older children and adolescents may be
able to produce a sputum sample for Gram stain and culture.
Sputum samples should be obtained in older children and
adolescents with severe pneumonia or pneumonia that has
failed to respond to treatment provided these children and
adolescents are able to expectorate sputum. A good quality
sputum specimen for testing should have less than 10 epithe-
lial cells and over 25 polymorphonuclear leucocytes per low
power field on Gram stain [12, 36].
In general, blood cultures are not necessary for nontoxic
looking children treated as outpatients but should be consid-
ered for those who require hospitalization, particularly those
with complicated pneumonia [10, 20, 44, 51]. Recent studies
have shown that blood cultures have a low yield (1 to 3%)
and do not appear helpful when collected in all children
without comorbidities hospitalized with uncomplicated
community-acquired pneumonia [35, 52, 53]. It is hoped that
future studies will help to identify the clinical characteristics
of those hospitalized children with community-acquired
pneumonia in whom obtaining blood cultures would lead to
changes in clinical management, reduction in unnecessary
venipuncture and testing, and cost-saving [53, 54].
Routine serologic testing for pathogens such as S. pneu-
moniae, M. pneumoniae, C. pneumoniae and viral agents is
of limited use because paired acute and convalescent serum
samples are required to demonstrate a fourfold or greater rise
in antibody titers to a specific pathogen for a diagnosis of
recent or current infection by that pathogen [10, 40]. In the
majority of cases, the infection usually has resolved by the
time the pathogen is confirmed serologically. Serologic test-
ing may be useful as an epidemiologic tool in establishing
the causative agent during an outbreak to define the inci-
dence and prevalence of the various respiratory pathogens
[36].
Community-Acquired Pneumonia Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2 139
Polymerase chain reaction (PCR) testing of respiratory
secretions from nasopharyngeal swabs/aspirates can be used
as a rapid diagnostic tool for bacterial pathogens (e.g., S.
pneumoniae, M. pneumoniae, C. pneumoniae) and viral
agents (e.g., respiratory syncytial virus, influenza viruses,
parainfluenza viruses, adenovirus, coronavirus, picornavirus,
and human metapneumovirus) [10, 35, 55, 56]. Rapid influ-
enza testing should be considered during flu season, as a
positive test is an indication for antiviral therapy [19]. PCR,
however, is expensive and not readily available outside refer-
ral centers.
7. DIAGNOSIS
The diagnosis is usually based on the clinical findings of
fever, cough, respiratory distress (e.g., tachypnea, intercos-
tal/subcostal/suprasternal retractions, nasal flaring, grunting),
and/or radiologic evidence of an acute pulmonary infil-
trate/consolidation [9, 12].
8. DIFFERENTIAL DIAGNOSIS
Pulmonary causes that may mimic community-acquired
pneumonia include asthma, bronchiolitis, pertussis, aspira-
tion syndromes, lung abscess, cystic fibrosis, bronchiectasis,
pulmonary atelectasis, pulmonary agenesis/hypoplasia, lobar
emphysema, cystic adenomatoid malformation, pulmonary
sequestration, and drug-induced pneumonitis [15]. Other
differential diagnosis includes sepsis, metabolic acidosis,
congestive heart failure, and vascular ring [40].
9. COMPLICATIONS
Community-acquired pneumonia has a negative impact
on quality of life as a result of physician visits, medical ex-
penses, discomfort experienced by the sick child, and loss of
working hours and income of parents who have to stay home
to look after the sick child [57]. Generally, complications are
more common in bacterial pneumonia than atypical or viral
pneumonia [12, 35]. Complications include bactere-
mia/septicemia, parapneumonic effusion, empyema, pneu-
matoceles, necrotizing pneumonia, lung abscess, bron-
chopleural fistula, and acute respiratory failure [9, 12, 15,
58-61]. Bacteremia/septicemia may, on occasions, lead to
brain abscess, meningitis, osteomyelitis, septic arthritis, peri-
carditis, and endocarditis [15]. Hyponatremia occurs in ap-
proximately 28 to 45% of children with community-acquired
pneumonia seen in the emergency department or at hospital
admission, and is usually mild [62-64]. Moderate or severe
hyponatremia is more commonly seen in patients with lobar-
segmental pneumonia [65]. Approximately 4% of children
with community-acquired pneumonia have hypoglycemia
which may be due to reduced caloric intake or the effect of
stress-induced cytokines during the infection [66]. Rarely,
hemolytic-uremic syndrome may occur with pneumococcal
pneumonia and influenza pneumonia [67].
10. TREATMENT
If viral pneumonia is suspected based on the history of
gradual onset, preceding upper respiratory tract infection,
mild symptoms, lack of toxicity, and diffuse auscultatory
findings, some authors suggest that such patients should not
be treated with antibiotics, especially if the child does not
have respiratory distress [2, 12, 68, 69]. An antiviral agent
such as oseltamivir (Tamiflu), zanamivir (Relenza), aman-
tadine (Symmetrel), or rimantadine (Flumadine) should be
initiated as soon as possible for influenza pneumonia, par-
ticularly for those with clinically worsening disease [2, 68].
Some authors suggest that antibiotic therapy should be initi-
ated in children suspected to have viral pneumonia if there is
deterioration in the clinical situation because of the possibil-
ity of bacterial superinfection [69].
The British Thoracic Society guidelines recommend that
children with a clear clinical diagnosis of pneumonia should
be treated with antibiotics, given that bacterial and viral
pneumonia cannot be reliably distinguished from each other
on clinical grounds [16]. In addition, in children with viral
pneumonia, coinfection with bacteria has been reported in up
to 30% of cases [12, 14, 69-73]. In practice, most children
with pneumonia are treated empirically with antibiotics; the
choice of which depends on the patient’s age and the most
likely pathogen. In previously healthy children under the age
of 5 years, amoxicillin (Amoxil, Moxatag, Trimox, Wymox)
80 to 90 mg/kg/day divided into two to three daily doses;
maximum 3 g/day) is the treatment of choice because it is
effective against the majority of pathogens which cause
community-acquired pneumonia in this age group [2, 6, 7,
44, 69]. High dose amoxicillin is chosen because of the pos-
sibility of resistant S. pneumoniae; the resistance of which
can be overcome at higher drug concentrations [12]. For
those with type 1 (immediate, anaphylactic-type) hypersensi-
tivity to penicillin, clindamycin (Cleocin HCL), azithromy-
cin (Zithromax), clarithromycin (Biaxin), and levofloxacin
(Levaquin) are reasonable alternatives [15, 68]. For children
with a non-type 1 hypersensitivity to penicillin, cepha-
losporins such as cefixime (Suprax), cefprozil (Cefzil), cef-
dinir (Omnicef), cefpodoxime (Vantin), and cefuroxime
(Ceftin) should be considered [68]. In previously healthy
children over the age of 5 years, macrolides such as azithro-
mycin (Zithromax) and clarithromycin (Biaxin) are the drugs
of choice given that in addition to S. pneumoniae, M. pneu-
moniae, and C. pneumonia are common pathogens in chil-
dren in this age group [2, 7, 12, 24, 42, 67, 68]. In communi-
ties with a high rate of pneumococcal resistance to penicillin,
levofloxacin (Levaquin), moxifloxacin (Avelox), and line-
zolid (Zyvox) should be considered [68]. For children with
community-acquired aspiration pneumonia, amoxicillin-
clavulanate (Augmentin) is the drug of choice [68]. Clin-
damycin (Cleocin HCL) is an alternative for those children
with type 1 hypersensitivity to penicillin [68].
The usual duration of antimicrobial therapy is 5 days for
azithromycin (Zithromax) and 7 to 10 days for other antimi-
crobial agents in patients with uncomplicated community-
acquired pneumonia [2, 15, 44, 68]. The duration of treat-
ment is considerably longer in those patients with severe
pneumonia caused by virulent pathogens, notably
methicillin-resistant S. aureus (MRSA), and those patients
with complications [2, 8].
Symptomatic therapy includes antipyretic and analgesic
medications such as acetaminophen/paracetamol (Tylenol,
Tempra, Panadol) and ibuprofen (Motrin, Advil) and main-
tenance of adequate hydration [74].
140 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2
All children should be re-examined within 48 to 72 hours
after the initiation of antibiotic treatment [2, 68]. At this
time, the majority of patients would show improvement in
clinical symptoms. If there is no improvement, patient com-
pliance, tolerability of antibiotic treatment, bacterial resis-
tance, and complications such as pleural effusion and em-
pyema should be considered [8, 23, 24].
Indications for hospital admissions include persistent
vomiting with inability to tolerate oral medication, signs of
dehydration, toxic appearance, altered mental status, suspi-
cion of pneumonia caused by a pathogen with high viru-
lence, development of complications, underlying conditions
that may predispose to a more serious course of the disease
or adversely affect response to treatment, hypoxemia (SaO2
< 90% in room air), cyanosis, marked tachypnea ( 70
breaths/min for infants;  50 breaths/min for older children),
apnea, nasal flaring, grunting, use of accessory muscles,
moderate/severe intercostal/subcostal/suprasternal retrac-
tions, and inadequate supervision by family [2, 3, 19, 35,
74].
Children hospitalized with influenza pneumonia should
be treated with an antiviral agent such as oseltamivir (Tami-
flu), zanamivir (Relenza), amantadine (Symmetrel), or
rimantadine (Flumadine) as soon as possible [2, 15, 68]. Un-
less one is certain that the cause of pneumonia is viral and
uncomplicated by secondary bacterial infection, treatment of
inpatients with pneumonia is empirical and often requires the
use of antibiotics. It has been shown that oral antibiotics are
as efficacious as parenteral antibiotics in the treatment of
community-acquired pneumonia [75, 76]. Parenteral antibi-
otics are indicated when oral fluid/medication cannot be tol-
erated or if there are signs of septicemia or complications
[77]. Ampicillin (Ampi, Omnipen, Principen) (150 to 200
mg/kg/day divided into 4 doses; maximum, 12 g/day), cefo-
taxime (Claforan) (150 mg/kg/day divided into 3 doses;
maximum, 10g/day), and ceftriaxone (Rocephin, Epicephin)
(50 to 100 mg/kg divided into 2 doses, maximum, 4 g/day)
are the drugs of choice [2, 74]. Ampicillin is usually given
intravenously while cefotaxime and ceftriaxone can be given
either intravenously or intramuscularly [2, 44]. The par-
enteral route can be transitioned to the oral route after the
patient has become afebrile for 24 to 48 hours and is able to
tolerate oral medication [15, 74]. A macrolide such as
azithromycin (Zithromax) or clarithromycin (Biaxin) may be
added if M. pneumoniae or C. pneumonia is suspected [2, 15,
74]. Levofloxacin (Levaquin) and moxifloxacin (Avelox) are
reasonable alternatives for the older child or adolescent with
suspected atypical pneumonia who may actually have pneu-
mococcal pneumonia [Barson d]. Vancomycin (Vancocin) or
clindamycin (Cleocin HCL) should be used if MRSA is a
consideration [2, 15, 35, 74]. Once a pathogen has been iden-
tified, antibiotic therapy can be adjusted to target the specific
pathogen [44].
Children admitted to hospital should be monitored with
continuous pulse oximetry [7]. Hypoxic children should be
given supplemental oxygen given by nasal cannulae,
headbox, face mask, or high flow delivery device to maintain
SaO2 > 92% [2, 6, 8]. Chest physiotherapy has no role in the
management of community-acquired pneumonia in children
[6-8, 78].
Leung et al.
It has been shown that corticosteroids inhibit the expres-
sion of many proinflammatory cytokines released as a result
of community-acquired pneumonia [79]. Therefore, systemic
corticosteroid therapy may be a useful adjunct in patients
with severe community-acquired pneumonia [51, 79]. Stern
et al. performed a meta-analysis on 17 randomized con-
trolled trials (n = 2,264) to assess the safety and efficacy of
systemic corticosteroids in the treatment of pneumonia [80].
Of the 17 randomized controlled trials, 13 trials involved
adult patients (n = 1,954) and 4 trials involved children (n =
310). The authors found that systemic corticosteroids signifi-
cantly reduced morbidity and mortality in adults with severe
community-acquired pneumonia and reduced morbidity for
adults and children with non-severe community-acquired
pneumonia. Systemic corticosteroid therapy, however, was
associated with more adverse events, particularly hypergly-
cemia [80]. It is hoped that future well-designed, large-scale,
randomized, placebo-controlled studies will help to define
which pediatric populations might benefit from systemic
corticosteroid therapy. Until then, the routine use of systemic
corticosteroid in children with community-acquired pneu-
monia cannot be justified.
11. PREVENTION
Breastfeeding should be encouraged since breastfeeding
has been shown to confer some protection to community-
acquired pneumonia especially in the first year of life [11, 81].
Vaccines play a critical role in the prevention of commu-
nity-acquired pneumonia. The use of the 13-valent conjugate
pneumococcal vaccine in children younger than 2 years of
age plus the use of the 23-valent polysaccharide pneumococ-
cal vaccine for children older than 2 years of age who have
certain underlying conditions (e.g., immunodeficiency, as-
plenia, chronic heart disease, chronic lung disease) have re-
sulted in a significant reduction in the incidence of commu-
nity-acquired pneumonia attributable to the pneumococcal
vaccine serotypes [82-86]. However, resistant serotypes have
emerged despite supposedly adequate vaccine coverage, es-
pecially serotype 3 in some countries [71, 72, 87]. Severe
complicated pneumonias continue to prevail [71, 72, 87].
The administration of Hib and annual influenza vaccines
are also associated with a reduction in community-acquired
pneumonia [1, 10, 24, 51]. As such, the administration of
appropriate pneumococcal, Hib, and influenza vaccines
should be strongly encouraged.
12. PROGNOSIS
Generally, the prognosis is good. The majority of other-
wise healthy children with community-acquired pneumonia
in developed countries recover without any long-term seque-
lae [15, 68]. Mortality is rare in developed countries and is
seen mainly in children with severe, underlying chronic dis-
ease [35]. Negative prognostic factors include preexisting
pulmonary disease, underlying cardiac disease, underlying
neuromuscular disease, and underlying immunodeficiency.
CONCLUSION
Community-acquired pneumonia is an important cause of
morbidity in developed countries and an important cause of
Community-Acquired Pneumonia Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2 141
morbidity and mortality in developing countries. Generally,
viruses are the most common cause of community-acquired
pneumonia in children younger than 5 years. Streptococcus
pneumoniae is the most common bacterial cause across all
age groups. Other important bacterial causes in children
younger than 5 years include Haemophilus influenzae, Strep-
tococcus pyogenes, Staphylococcus aureus, Moraxella
catarrhalis, and Mycoplasma pneumoniae. In children 5
years or older, in addition to S. pneumoniae, other important
bacterial causes include Mycoplasma pneumoniae and
Chlamydophila pneumonia. The British Thoracic Society
guidelines recommend that children with a clear clinical di-
agnosis should be treated with antibiotics, given that bacte-
rial and viral pneumonia cannot be reliably distinguished
from each other on clinical grounds. In addition, in children
with viral pneumonia, coinfection with bacteria has been
reported in up to 30% of cases. In practice, most children
with pneumonia are treated empirically with antibiotics; the
choice of which depends on the patient’s age and the most
likely pathogen. In previously healthy children under the age
of 5 years, amoxicillin 80 to 90 mg/kg/day divided into two
to three daily doses is the treatment of choice because it is
effective against the majority of pathogens which cause
community-acquired pneumonia in this age group. For those
with type 1 hypersensitivity to penicillin, clindamycin,
azithromycin, clarithromycin, and levofloxacin are reason-
able alternatives. For children with a non-type 1 hypersensi-
tivity to penicillin, cephalosporins such as cefixime,
cefprozil, cefdinir, cefpodoxime, and cefuroxime should be
considered. In previously healthy children over the age of 5
years, macrolides such as azithromycin (Zithromax) and
clarithromycin (Biaxin) are the drugs of choice given that in
addition to S. pneumoniae, M. pneumoniae, and C. pneumo-
nia are common pathogens in children in this age group. In
communities with a high rate of pneumococcal resistance to
penicillin, levofloxacin, moxifloxacin, and linezolid should
be considered.
CURRENT & FUTURE DEVELOPMENTS
The development of new vaccines or improvement of
existing vaccines may be of potential use in the prevention of
community-acquired pneumonia. Denoel et al. disclosed an
invention relating to immunogenic compositions of unconju-
gated S. pneumoniae proteins selected from pneumolysin and
member (s) of the polyhistidine triad family (e.g. PhtD), in
combination with an adjuvant comprising QS21, monophos-
phoryl lipid A (MPL), phospholipid and sterol, presented in
the form of a liposome [88]. The authors claimed that the
vaccine manufactured with the above constituents has en-
hanced immunogenicity.
In view of the emergence of antibiotic resistance, antibi-
otics should not be over-prescribed and that the development
of new and effective antibiotics, particularly for pneumonia
caused by multi-drug resistant S. pneumoniae, macrolide-
resistant M. pneumoniae, and MRSA, cannot be overempha-
sized [89].
Ceftaroline fosamil (Cteflaro, Zinforo), a fifth-generation
cephalosporin, has broad-spectrum activity against Gram-
positive and Gram-negative bacteria, including MRSA and
both penicillin-non-susceptible and multi-drug resistant
strains of S. pneumoniae [90, 91]. In a recent prospective
study of 134 clinically evaluable children hospitalized with
confirmed community-acquired pneumonia, Cannavino et al.
randomized (3:1) these children to receive either intravenous
ceftaroline fosamil (n = 98) or ceftriaxone (n = 36) [90]. The
authors found that ceftaroline fosamil was well tolerated and
had high and comparable outcomes compared with ceftriax-
one in the treatment of community-acquired pneumonia in
hospitalized children. Wieser et al. patented an invention
relating to methods for the preparation of novel crystalline
forms of ceftaroline fosamil (Teflaro) [92]. Ceftaroline
fosamil is a prodrug with improved solubility compared to
its active metabolite ceftaroline. The crystalline forms of
ceftaroline fosamil have a constant pKa value over a broad
range of relative humidity and consequently do not require
controlled and expensive storage conditions or special and
expensive packaging.
Tebipenem pivoxil, an oral carbapenem antibiotic, is safe
and efficacious for treating pediatric community-acquired
pneumonia [93]. In Japan, it is the drug of choice for com-
munity-acquired pneumonia caused by penicillin and mac-
rolide-resistant S. pneumoniae and
-lactamase non-
producing ampicillin-resistant H. influenzae [93]. Shi et al.
disclosed the preparation methods of two crystalline forms of
tebipenem [94]. The crystalline forms of tebipenem have
good stability, fine color (white), high purity, and low heavy
metal residue and are more suitable for storage and used as
active pharmaceutical ingredients [94].
Fatheree et al. disclosed an invention which provides a
novel cross-linked glycopeptide-cephalosporin compound
[95]. The compound has a unique chemical structure in
which a glycopeptide is covalently linked to a pyridinium
moiety of a cephalosporin. Among other properties, the
compound possesses surprising and unexpected potency
against Gram-positive bacteria including MRSA [89]. The
medication is given intravenously and has the potential to be
used for the treatment of severe community-acquired pneu-
monia [89].
OP0595 is a new diazabicyclooctane which acts in three
ways, namely, as an antibiotic agent against Enterobacte-
riaceae, as a
-lactamase inhibitor, and as an “enhancer” of
the activity of various
-lactam agents [96, 97]. It has the
potential of overcoming bacterial resistance when combined
with various
-lactam agents [89, 96, 97]. The medication is
given intravenously and has the potential to be used for the
treatment of severe community-acquired pneumonia [89].
Abe et al. disclosed the production methods of
diazabicyclooctane derivative as well as its crystalline forms
[98, 99]. Ogawa et al. disclosed the process for producing
lyophilized forms of diazabicyclooctane derivative from the
crystalline forms; the lyophilized forms have a more desir-
able storage stability [100].
Nafithromycin, a novel lactone ketolide antibiotic, is now
in phase II development targeting at multidrug-resistant S.
pneumoniae [101]. The drug is capable of passing through
the alveolar capillary wall to achieve a high and sustained
level in the epithelial lining fluid and alveolar macrophage
thus is ideal for the treatment of community-acquired pneu-
monia [102].
142 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2
Avarofloxacin, a novel, fifth-generation fluoroquinolone,
has excellent in vitro and in vivo activity against a variety of
Gram-negative and Gram-positive microorganisms [103]. It
has potent activity against pathogens (such as S. pneumoniae
and S. aureus) responsible for community-acquired pneumo-
nia [103]. Avarofloxacin has been shown to be effective
against drug-resistant S. pneumoniae, MRSA, and ciproflox-
acin-resistant MRSA [103]. The medication can be given
orally and parenterally and shows promise as an effective
agent for the treatment of community-acquired pneumonia
[103].
Solithromycin, a fourth generation macrolide, shows high
affinity for the ribosomes of Gram-negative and Gram-
positive microorganisms [104]. Recent phase II/III trials
have demonstrated solithromycin has efficacy comparable to
that of moxifloxacin or levofloxacin in the treatment of
community-acquired pneumonia [104]. Solithromycin can be
given orally and parenterally. Cusak and Maras disclosed an
invention relating to an efficient route of synthesis of
solithromycin and to a method of its purification which obvi-
ates the necessity of chromatographic purifications and im-
proves the quality of the product by efficiently removing
impurities [105]. The tablet form of solithromycin was pat-
ented by Shimada et al. [106]. Solithromycin has a favorable
tolerability and safety profile [106].
Langohr et al. disclosed an invention comprising a hu-
man plasma-derived IgM-enriched immunoglobulin prepara-
tion which has not been chemically modified and/or treated
with beta- propiolactone [107]. The authors claimed that the
preparation can be used as adjunctive treatment for severe
community-acquired pneumonia.
Well-designed, large-scale, randomized, double-blind,
and placebo-controlled studies should be done to compare
the efficacy of new antibiotics/agents with the current ones
that are known to work. This is especially vital for the treat-
ment of very young children (< 2 months) with community-
acquired pneumonia and children with complicated commu-
nity-acquired pneumonia. The optimal dose and duration of
treatment have to be determined.
ETHICS APPROVAL AND CONSENT TO PARTICI-
PATE
Not applicable.
HUMAN AND ANIMAL RIGHTS
No Animals/Humans were used for studies that are the
basis of this research.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
Professor Alexander K.C. Leung, and Dr. Alex H.C. Wong,
and Professor Kam Lun Hon confirm that this article has no
conflicts of interest.
Professor Leung, Dr. Wong, and Professor Hon disclose
no relevant financial relationship. The authors confirm that
this article content has no conflict of interest.
Leung et al.
ACKNOWLEDGEMENTS
Professor Alexander K.C. Leung is the principal author.
Dr. Alex H.C. Wong and Professor Kam Lun Hon are the co-
authors who contributed and helped with the drafting of this
manuscript.
REFERENCES
[1] Barson W. Pneumonia in children: Epidemiology, pathogenesis,
and etiology. In: Post TW, ed. UpToDate. Waltham, MA. (Ac-
cessed on January 28, 2018).
[2] Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER,
Harrison C, et al. Executive summary: The management of com-
munity-acquired pneumonia in infants and children older than 3
months of age: Clinical practice guidelines by the Pediatric Infec-
tious Diseases Society and the Infectious Diseases Society of
America. Clin Infect Dis 2011; 53(7): 617-30.
[3] Qin Q, Shen KL. Community-acquired pneumonia and its compli-
cations. Indian J Pediatr 2015; 82(8): 745-51.
[4] Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO Child Health
Epidemiology Reference Group. WHO estimates of the causes of
death in children. Lancet 2005; 365(9465): 1147-52.
[5] Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C,
et al. Community-acquired pneumonia requiring hospitalization
among U.S. children. N Engl J Med 2015; 372(9): 835-45.
[6] Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M,
et al. British Thoracic Society guidelines for the management of
community acquired pneumonia in children: update 2011. Thorax
2011; 66(Suppl 2): 1-23.
[7] British Thoracic Society Standards of Care Committee. British
Thoracic Society Guidelines for the Management of Community
Acquired Pneumonia in Childhood. Thorax 2002; 57(Suppl 1): 1-
24.
[8] Chetty K, Thomson AH. Management of community-acquired
pneumonia in children. Paediatr Drugs 2007; 9(6): 401-11.
[9] Messinger AI, Kupfer O, Hurst A, Parker S. Management of pedi-
atric community-acquired bacterial pneumonia. Pediatr Rev 2017;
38(9): 394-409.
[10] Stein RT, Marostica PJ. Community-acquired pneumonia: A re-
view and recent advances. Pediatr Pulmonol 2007; 42(12): 1095-
1103.
[11] Stuckey-Schrock K, Hayes BL, George CM. Community-acquired
pneumonia in children. Am Fam Physician 2012; 86(7): 661-67.
[12] Atkinson M, Yanney M, Stephenson T, Smyth A. Effective treat-
ment strategies for paediatric community-acquired pneumonia. Ex-
pert Opin Pharmacother 2007; 8(8): 1091-101.
[13] Chiappini E, Venturini E, Galli L, Novelli V, de Martino M. Diag-
nostic features of community-acquired pneumonia in children:
What's new? Acta Paediatr 2013; 102(465): 17-24.
[14] Wallihan R, Ramilo O. Community-acquired pneumonia in chil-
dren: Current challenges and future directions. J Infect 2014;
69(Suppl 1): S87-90.
[15] Ampofo K. Community-acquired pneumonia. In: McMillan J,
Barrett D, Boney C, eds. Clinical Decision Support: Pediatrics.
Wilmington, Delaware: Decision Support in Medicine, LLC, 2015,
electronic database.
URL:http://www.decisionsupportinmedicine.com (Accessed on
January 20, 2018)
[16] Cardinale F, Cappiello AR, Mastrototaro MF, Pignatelli M, Espo-
sito S. Community-acquired pneumonia in children. Early Hum
Dev 2013; 89(Suppl 3): S49-52.
[17] Esposito S, Cohen R, Domingo JD, Pecurariu OF, Greenberg D,
Heininger U, et al. Antibiotic therapy for pediatric community-
acquired pneumonia: Do we know when, what and for how long to
treat? Pediatr Infect Dis J 2012; 31(6): e78-85.
[18] García-García ML, Calvo C, Pozo F, Villadangos PA, Pérez-Breña
P, Casas I. Spectrum of respiratory viruses in children with com-
munity-acquired pneumonia. Pediatr Infect Dis J 2012; 31(8): 808-
13.
[19] Posten S, Reed J. Pediatric community acquired pneumonia. S D
Med 2017; 70(12): 557-61.
[20] Capelastegui A, España PP, Bilbao A, Gamazo J, Medel F, Salgado
J, et al. Etiology of community-acquired pneumonia in a popula-
tion-based study: Link between etiology and patients characteris-
Community-Acquired Pneumonia Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2 143
tics, process-of-care, clinical evolution and outcomes. BMC Infect
Dis. 2012; 12: 134.
[21] Das A, Patgiri SJ, Saikia L, Dowerah P, Nath R. Bacterial patho-
gens associated with community-acquired pneumonia in children
aged below five years. Indian Pediatr 2016; 53(3): 225-27.
[22] Haq IJ, Battersby AC, Eastham K, McKean M. Community ac-
quired pneumonia in children. BMJ 2017; 356: j686.
[23] Iroh Tam PY. Approach to common bacterial infections: Commu-
nity-acquired pneumonia. Pediatr Clin North Am 2013; 60(2): 437-
53.
[24] Dennehy PH. Community-acquired pneumonia in children. Med
Health R I 2010; 93(7): 211-15.
[25] Leung AK, Robson WL, Davies HD. Pertussis in adolescents. Adv
Ther 2007; 24(2): 353-61.
[26] Medjo B, Atanaskovic-Markovic M, Radic S, Nikolic D, Lukac M,
Djukic S. Mycoplasma pneumoniae as a causative agent of com-
munity-acquired pneumonia in children: Clinical features and labo-
ratory diagnosis. Ital J Pediatr 2014; 40: 104.
[27] Scott JA, Brooks WA, Peiris JS, Holtzman D, Mulholland EK.
Pneumonia research to reduce childhood mortality in the develop-
ing world. J Clin Invest 2008; 118(4): 1291-300.
[28] Juvén T, Mertsola J, Waris M, Leinonen M, Meurman O,
Roivainen M, et al. Etiology of community-acquired pneumonia in
254 hospitalized children. Pediatr Infect Dis J 2000; 19(4): 293-98.
[29] Ruuskanen O, Mertsola J. Childhood community-acquired pneu-
monia. Semin Respir Infect 1999; 14(2): 163-172.
[30] Clark JE, Hammal D, Hampton F, Spencer D, Parker L. Epidemi-
ology of community-acquired pneumonia in children seen in hospi-
tal. Epidemiol Infect 2007; 135(2): 262-69.
[31] Koshy E, Murray J, Bottle A, Sharland M, Saxena S. Impact of the
seven-valent pneumococcal conjugate vaccination (PCV7) pro-
gramme on childhood hospital admissions for bacterial pneumonia
and empyema in England: National time-trends study, 1997-2008.
Thorax 2010; 65(9): 770-74.
[32] Grijalva CG, Nuorti JP, Zhu Y, Griffin MR. Increasing incidence
of empyema complicating childhood community-acquired pneu-
monia in the United States. Clin Infect Dis 2010; 50(6): 805-13.
[33] Thomson A, Harris M. Community-acquired pneumonia in chil-
dren: What's new? Thorax 2011; 66(10): 927-28.
[34] Pelton SI, Hammerschlag MR. Overcoming current obstacles in the
management of bacterial community-acquired pneumonia in ambu-
latory children. Clin Pediatr (Phila) 2005; 44(1): 1-17.
[35] Boyd K. Back to the basics: Community-acquired pneumonia in
children. Pediatr Ann 2017; 46(7): e257-e61.
[36] Ostapchuk M, Roberts DM, Haddy R. Community-acquired pneu-
monia in infants and children. Am Fam Physician 2004; 70(5):
899-908.
[37] Grant CC, Emery D, Milne T, Coster G, Forrest CB, Wall CR,
et al. Risk factors for community-acquired pneumonia in pre-
school-aged children. J Paediatr Child Health 2012; 48(5): 402-12.
[38] Heiskanen-Kosma T, Korppi M. Risk factors of community-
acquired pneumonia in children. Eur Respir J 2010; 36(5): 1221-
1222.
[39] Greenberg D, Leibovitz E. Community-acquired pneumonia in
children: from diagnosis to treatment. Chang Gung Med J 2005;
28(11): 746-52.
[40] Barson W. Community-acquired pneumonia in children: Clinical
features and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA.
(Accessed on January 28, 2018)
[41] Florin TA, Ambroggio L, Brokamp C, Rattan MS, Crotty EJ,
Kachelmeyer A, et al. Reliability of examination findings in sus-
pected community-acquired pneumonia. Pediatrics 2017; 140(3).
pii: e20170310.
[42] Sinaniotis CA, Sinaniotis AC. Community-acquired pneumonia in
children. Curr Opin Pulm Med 2005; 11(3): 218-25.
[43] Jadavji T, Law B, Lebel MH, Kennedy WA, Gold R, Wang EE. A
practical guide for the diagnosis and treatment of pediatric pneu-
monia. CMAJ 1997; 156(5): S703-S11.
[44] Schauner S, Erickson C, Fadare K, Stephens K. Community-
acquired pneumonia in children: A look at the IDSA guidelines. J
Fam Pract 2013; 62(1): 9-15.
[45] Boursiani C, Tsolia M, Koumanidou C, Malagari A, Vakaki M,
Karapostolakis G, et al. Lung ultrasound as first-line examination
for the diagnosis of community-acquired pneumonia in children.
Pediatr Emerg Care 2017; 33(1): 62-66.
[46] Chen IC, Lin MY, Liu YC, Cheng HC, Wu JR, Hsu JH, et al. The
role of transthoracic ultrasonography in predicting the outcome of
community-acquired pneumonia in hospitalized children. PLoS
One 2017; 12(3): e0173343.
[47] Ho MC, Ker CR, Hsu JH, Wu JR, Dai ZK, Chen IC. Usefulness of
lung ultrasound in the diagnosis of community-acquired pneumonia
in children. Pediatr Neonatol 2015; 56(1): 40-45.
[48] Urbankowska E, Krenke K, Drobczyski , Korczyski P, Ur-
bankowski T, Krawiec M, et al. Lung ultrasound in the diagnosis
and monitoring of community acquired pneumonia in children.
Respir Med 2015; 109(9): 1207-12.
[49] Yilmaz HL, Özkaya AK, Sarı Gökay S, Tolu Kendir Ö, enol H.
Point-of-care lung ultrasound in children with community acquired
pneumonia. Am J Emerg Med 2017; 35(7): 964-69.
[50] Johansson N, Kalin M, Backman-Johansson C, Larsson A, Nilsson
K, Hedlund J. Procalcitonin levels in community-acquired pneu-
monia – correlation with aetiology and severity. Scand J Infect Dis
2014; 46(11): 787-91.
[51] Iroh Tam PY, Bernstein E, Ma X, Ferrieri P. Blood culture in
evaluation of pediatric community-acquired pneumonia: A system-
atic review and meta-analysis. Hosp Pediatr 2015; 5(6): 324-36.
[52] Davis TR, Evans HR, Murtas J, Weisman A, Francis JL, Khan A.
Utility of blood cultures in children admitted to hospital with com-
munity-acquired pneumonia. J Paediatr Child Health 2017; 53(3):
232-36.
[53] Neuman MI, Hall M, Lipsett SC, Hersh AL, Williams DJ, Gerber
JS, et al. Utility of blood culture among children hospitalized with
community-acquired pneumonia. Pediatrics 2017; 140(3). pii:
e20171013. doi: 10.1542/peds.2017-1013.
[54] McCulloh RJ. Targeted blood culture testing in pediatric commu-
nity-acquired pneumonia. J Pediatr 2016; 172: 226-27.
[55] Mustafa MI, Al-Marzooq F, How SH, Kuan YC, Ng TH. The use
of multiplex real-time PCR improves the detection of the bacterial
etiology of community acquired pneumonia. Trop Biomed 2011;
28(3): 531-44.
[56] Okada T, Morozumi M, Sakata H, Takayanagi R, Ishiwada N, Sato
Y, et al. A practical approach estimating etiologic agents using
real-time PCR in pediatric inpatients with community-acquired
pneumonia. J Infect Chemother 2012; 18(6): 832-40.
[57] Shoham Y, Dagan R, Givon-Lavi N, Liss Z, Shagan T, Zamir O,
et al. Community-acquired pneumonia in children: Quantifying the
burden on patients and their families including decrease in quality
of life. Pediatrics 2005; 115(5): 1213-19.
[58] Abu-Kishk I, Zohar E, Berkovitch M, Kozer E, Seguier-Lipszyc E,
Klin B, et al. Factors associated with empyema in children with
community acquired pneumonia. Minerva Pediatr 2015; 67(6):
473-79.
[59] Esposito S, Marchese A, Tozzi AE, Rossi GA, Da Dalt L, Bona G,
et al. Bacteremic pneumococcal community-acquired pneumonia in
children less than 5 years of age in Italy. Pediatr Infect Dis J 2012;
31(7): 705-10.
[60] Krenke K, Urbankowska E, Urbankowski T, Lange J, Kulus M.
Clinical characteristics of 323 children with parapneumonic pleural
effusion and pleural empyema due to community acquired pneu-
monia. J Infect Chemother 2016; 22(5): 292-97.
[61] Langley JM, Kellner JD, Solomon N, Robinson JL, Le Saux N,
McDonald J, et al. Empyema associated with community-acquired
pneumonia: A Pediatric Investigator's Collaborative Network on
Infections in Canada (PICNIC) study. BMC Infect Dis 2008; 8:
129.
[62] Don M, Valerio G, Korppi M, Canciani M. Radiologic predictors
of hyponatremia in children hospitalized with community-acquired
pneumonia. Pediatr Nephrol 2008; 23(12): 2247-53.
[63] Don M, Valerio G, Canciani M, Korppi M. Hyponatremia in radi-
ologically confirmed pediatric community-acquired pneumonia.
Pediatr Emerg Care 2014; 30(1): 76.
[64] Nair V, Niederman MS, Masani N, Fishbane S. Hyponatremia in
community-acquired pneumonia. Am J Nephrol 2007; 27(2): 184-
190.
[65] Glatstein M, Rozen R, Scolnik D, Rimon A, Grisaru-Soen G,
Freedman S, et al. Radiologic predictors of hyponatremia in chil-
dren hospitalized with community-acquired pneumonia. Pediatr
Emerg Care 2012; 28(8): 764-66.
[66] Don M, Valerio G, Korppi M, Canciani M. Hyper- and hypogly-
cemia in children with community-acquired pneumonia. J Pediatr
Endocrinol Metab 2008; 21(7): 657-64.
144 Recent Patents on Inflammation & Allergy Drug Discovery 2018, Vol. 12, No. 2
[67] Robson WL, Leung AK, Kaplan BS. Hemolytic-uremic syndrome.
Curr Probl Pediatr 1993; 23(1): 16-33.
[68] Barson W. Community-acquired pneumonia in children: Outpatient [88]
treatment. In: Post TW, ed. UpToDate. Waltham, MA. (Accessed
on January 28, 2018) [89]
[69] Kelly MS, Sandora TJ. community-acquired pneumonia. In:
Kliegman RM, Stanton BM, St. Geme J, Schor NF, Behrman RE,
eds. Nelson Textbook of Pediatrics, 20th edition. Philadelphia: El- [90]
sevier Saunders, 2015, pp2088-94.
[70] Hon KL, Ip M, Chu WC, Wong W. Megapneumonia coinfection:
Pneumococcus, Mycoplasma pneumoniae, and Metapneumovirus.
Case Rep Med 2012; 2012: 310104. [91]
[71] Hon KL, Fu A, Leung TF, Poon TC, Cheung WH, Fong CY, et al.
Cardiopulmonary morbidity of streptococcal infections in a PICU.
Clin Respir J 2015; 9(1): 45-52. [92]
[72] Hon KL, Leung AS, Cheung KL, Fu AC, Chu WC, Ip M, et al.
Typical or atypical pneumonia and severe acute respiratory symp-
toms in PICU. Clin Respir J 2015; 9(3): 366-71. [93]
[73] Hon KL, Luk MP, Fung WM, Li CY, Yeung HL, Liu PK, et al.
Mortality, length of stay, bloodstream and respiratory viral infec-
tions in a pediatric intensive care unit. J Crit Care 2017; 38: 57-61.
[74] Barson W. Community-acquired pneumonia in children: Inpatient [94]
treatment. In: Post TW, ed. UpToDate. Waltham, MA. (Accessed
on January 28, 2018).
[75] Don M, Canciani M, Korppi M. Community-acquired pneumonia [95]
in children: What's old? What's new? Acta Paediatr 2010; 99(11):
1602-08.
[76] Wilder RA. Question 1 Are oral antibiotics as efficacious as intra- [96]
venous antibiotics for the treatment of community acquired pneu-
monia? Arch Dis Child 2011; 96(1): 103-4.
[77] Korppi M. Diagnosis and treatment of community-acquired pneu-
monia in children. Acta Paediatr 2012; 101(7): 702-4. [97]
[78] Lukrafka JL, Fuchs SC, Fischer GB, Flores JA, Fachel JM, Castro-
Rodriguez JA. Chest physiotherapy in paediatric patients hospital-
ised with community-acquired pneumonia: A randomised clinical
trial. Arch Dis Child 2012; 97(11): 967-71.
[79] Weiss AK, Hall M, Lee GE, Kronman MP, Sheffler-Collins S, [98]
Shah SS. Adjunct corticosteroids in children hospitalized with
community-acquired pneumonia. Pediatrics 2011; 127(2): e255-
363. [99]
[80] Stern A, Skalsky K, Avni T, Carrara E, Leibovici L, Paul M. Corti-
costeroids for pneumonia. Cochrane Database Syst Rev 2017 Dec
13;12:CD007720. [100]
[81] Leung AK, Sauve RS. Breast is best for babies. J Natl Med Assoc
2005;97(7):1010-1019.
[82] Hasegawa J, Mori M, Ohnishi H, Tsugawa T, Hori T, Yoto Y, et al. [101]
Pneumococcal vaccination reduces the risk of community-acquired
pneumonia in children. Pediatr Int 2017; 59(3): 316-20.
[83] Naito S, Tanaka J, Nagashima K, Chang B, Hishiki H, Takahashi
Y, et al. The impact of heptavalent pneumococcal conjugate vac-
cine on the incidence of childhood community-acquired pneumonia [102]
and bacteriologically confirmed pneumococcal pneumonia in Ja-
pan. Epidemiol Infect 2016; 144(3): 494-506.
[84] Principi N, Esposito S. Prevention of community-acquired pneu-
monia with available pneumococcal vaccines. Int J Mol Sci 2016
Dec 25;18(1). pii: E30. doi: 10.3390/ijms18010030. [103]
[85] Silva SR, Mello LM, Silva AS, Nunes AA. Impact of the pneumo-
coccal 10-valent vaccine on reducing hospitalization for commu-
nity-acquired pneumonia in children. Rev Paul Pediatr 2016; 34(4):
418-24. [104]
[86] Sterky E, Bennet R, Lindstrand A, Eriksson M, Nilsson A. The
impact of pneumococcal conjugate vaccine on community-acquired
pneumonia hospitalizations in children with comorbidity. Eur J Pe- [105]
diatr 2017; 176(3): 337-42.
[87] Hon KL, Chan KH, Ko PL, Cheung MHY, Tsang KYC, Chan [106]
LCN, et al. Change in pneumococcus serotypes but not mortality or
morbidity in pre- and post-13-valent polysaccharide conjugate vac- [107]
cine era: epidemiology in a pediatric intensive care unit over 10
Leung et al.
years. J Trop Pediatr 2017 Nov 6. doi: 10.1093/tropej/fmx084.
[Epub ahead of print]
Denoel, P., Poolman, J., Verlant, V., Wallemacq, H. Vaccine
against Streptococcus pneumoniae. US20140072622 (2014).
Liapikou A, Cillóniz C, Torres A. Investigational drugs in Phase I
and Phase II clinical trials for the treatment of community-acquired
pneumonia. Expert Opin Investig Drugs 2017; 26(11): 1239-48.
Cannavino CR, Nemeth A, Korczowski B, Bradley JS, O'Neal T,
Jandourek A, et al. A randomized, prospective study of pediatric
patients with community-acquired pneumonia treated with ceftaro-
line versus ceftriaxone. Pediatr Infect Dis J 2016; 35(7): 752-59.
El Hajj MS, Turgeon RD, Wilby KJ. Ceftaroline fosamil for com-
munity-acquired pneumonia and skin and skin structure infections:
A systematic review. Int J Clin Pharm 2017; 39(1): 26-32.
Wieser, J., Sturm, H., Pichler, A., Hotter, A., Martin, N., Langes,
C., et al. Novel crystalline forms of ceftaroline fosamil.
US20160200750 (2016).
Sakata H, Kuroki H, Ouchi K, Tajima T, Iwata S. World's First
Oral Carbapenem Study Group. Pediatric community-acquired
pneumonia treated with a three-day course of tebipenem pivoxil. J
Infect Chemother 2017; 23(5): 307-11.
Shi, Y., Zhang, Di, H., Zhang, Z. Crystalline forms of tebipenem,
preparation methods and uses thereof in the preparation of medi-
cines. WO2012139424 (2012).
Fatheree, P.R., Linsell, M.S., Marquess, D., Trapp, S.G., Moran,
E.J., Aggen, J.B. Cross-linked glycopeptide-cephalosporin antibiot-
ics. JP2013047267 (2013).
Morinaka A, Tsutsumi Y, Yamada M, Suzuki K, Watanabe T, Abe
T, et al. OP0595, a new diazabicyclooctane: mode of action as a
serine
-lactamase inhibitor, antibiotic and
-lactam 'enhancer'. J
Antimicrob Chemother 2015; 70(10): 2779-86.
Morinaka A, Tsutsumi Y, Yamada K, Takayama Y, Sakakibara S,
Takata T, et al. In vitro and in vivo activities of OP0595, a new di-
azabicyclooctane, against CTX-M-15-positive Escherichia coli and
KPC-positive Klebsiella pneumoniae. Antimicrob Agents Che-
mother 2016; 60(5): 3001-16.
Abe, T., Furuuchi, T., Sakamaki, Y., Mitsuhashi, N., Saito, Y.
Crystalline forms of diazabicyclooctane derivative and production
process thereof. US20160272641 (2016).
Abe, T., Furuuchi, T., Sakamaki, Y., Mitsuhashi, N., Saito, Y.
Process for producing of diazabicyclooctane derivative.
US20170283415 (2017).
Ogawa, T., Yokoyama, T., Furuyama, S., Ichiki, M., Fushihara, K.
Production process of crystals of diazabicyclooctane derivative and
stable lyophilized preparation. US20170327499 (2017).
Flamm RK, Rhomberg PR, Sader HS. In vitro activity of the novel
lactone ketolide nafithromycin (WCK 4873) against contemporary
clinical bacteria from a global surveillance program. Antimicrob
Agents Chemother 2017; 61(12). pii: e01230-17. doi:
10.1128/AAC.01230-17.
Rodvold KA, Gotfried MH, Chugh R, Gupta M, Friedland HD,
Bhatia A. Comparison of plasma and intrapulmonary concentra-
tions of nafithromycin (WCK 4873) in healthy adult subjects. An-
timicrob Agents Chemother 2017; 61(9). pii: e01096-17. doi:
10.1128/AAC.01096-17.
Jones TM, Johnson SW, DiMondi VP, Wilson DT. Focus on JNJ-
Q2, a novel fluoroquinolone, for the management of community-
acquired bacterial pneumonia and acute bacterial skin and skin
structure infections. Infect Drug Resist 2016; 9: 119-128.
Viasus D, Ramos O, Ramos L, Simonetti AF, Carratalà J.
Solithromycin for the treatment of community-acquired bacterial
pneumonia. Expert Rev Respir Med 2017; 11(1): 5-12.
Cusak, A., Maras, N. A novel synthetic pathway towards
solithromycin and purification thereof. WO2017118690 (2017).
Shimada, Y., Kubo, Y., Oura, T., Oishi, T. Tablet containing
solithromycin. WO2017061431 (2017).
Langohr, P., Wartenberg-Demand, A., Ulrike, W., Daelken, B.
Treatment of severe community acquired pneumonia.
WO2017157850 (2017).