Community-acquired pneumonia (CAP) occurs more often in early childhood than at almost any other age. Many microorganisms are associated with pneumonia, but individual pathogens are difficult to identify, which poses problems in antibiotic management. This article reviews the common as well as new, emerging pathogens, as well as the guidelines for management of pediatric CAP. Current guidelines for pediatric CAP continue to recommend the use of high-dose amoxicillin for bacterial CAP and azithromycin for suspected atypical CAP (usually caused by Mycoplasma pneumoniae ) in children.
Key points
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The diagnosis of community-acquired pneumonia (CAP) in children is not very sensitive or specific.
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Causative pathogens are challenging to isolate, and age is the best predictor of cause.
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A substantial proportion of CAP is mixed bacterial and viral infections; overdiagnosis of mild to moderate CAP can lead to overtreatment.
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The difficulty in differentiating between bacterial and viral pneumonia often leads to unnecessary antibiotic use.
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Current guidelines by the Pediatrics Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) recommend amoxicillin (90 mg/kg/d orally in 2 doses) as the primary therapy for presumed bacterial pneumonia and azithromycin (10 mg/kg on day 1, followed by 5 mg/kg once daily on days 2–5) as the primary therapy for presumed atypical pneumonia in children younger than 5 years or aged 5 years or older.
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For children aged 5 years or older with presumed bacterial CAP who do not have clinical, laboratory, or radiographic evidence that distinguish bacterial CAP from atypical CAP, PIDS/IDSA guidelines note that a macrolide can be added to the β-lactam antibiotic.
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Much of the pediatric CAP guidelines is based on evidence of poor to moderate quality, and there many gaps in the evidence remain.
Introduction
Community-acquired pneumonia (CAP) is fundamentally different in children and in adults. The evaluation, diagnosis, and treatment that distinguish the approach to management in children from that of adult disease is based on the differing causes of childhood pneumonia, and this microbial spectrum has changed over the past 3 decades with the introduction of conjugate vaccines and improved molecular diagnostic assays.
There are 2 main challenges in the diagnosis of CAP: the first is the definition of CAP, particularly in young children, in whom bacterial and viral infections can occur with similar frequencies, and in whom overdiagnosis of mild symptoms and signs may lead to unnecessary antibiotic use; the second is the identification of a causative pathogen, which is frequently impractical and inadequate in children, and in whom the failure to isolate an organism can result in unnecessary antibiotic use. These problems affect the management of CAP, and lead to emergence of resistance as a result of overtreatment. Management decisions are complicated because there are few randomized controlled trials in children that evaluate different antibiotic therapies and treatment duration. Although guidelines exist, they are often based on poor-quality evidence.
The challenge for the general pediatrician is to recognize lower respiratory tract illness, to refer for hospitalization when it is severe, and to appropriately treat with antibiotics if a bacterial pneumonia is suspected. This review focuses on practical issues of clinical relevance for the general pediatrician, including what to elicit from the patient history and examination, keeping in mind not only the infections that are commonly seen but also emerging infectious diseases and those that are less frequently seen but that are severe when they occur.
Introduction
Community-acquired pneumonia (CAP) is fundamentally different in children and in adults. The evaluation, diagnosis, and treatment that distinguish the approach to management in children from that of adult disease is based on the differing causes of childhood pneumonia, and this microbial spectrum has changed over the past 3 decades with the introduction of conjugate vaccines and improved molecular diagnostic assays.
There are 2 main challenges in the diagnosis of CAP: the first is the definition of CAP, particularly in young children, in whom bacterial and viral infections can occur with similar frequencies, and in whom overdiagnosis of mild symptoms and signs may lead to unnecessary antibiotic use; the second is the identification of a causative pathogen, which is frequently impractical and inadequate in children, and in whom the failure to isolate an organism can result in unnecessary antibiotic use. These problems affect the management of CAP, and lead to emergence of resistance as a result of overtreatment. Management decisions are complicated because there are few randomized controlled trials in children that evaluate different antibiotic therapies and treatment duration. Although guidelines exist, they are often based on poor-quality evidence.
The challenge for the general pediatrician is to recognize lower respiratory tract illness, to refer for hospitalization when it is severe, and to appropriately treat with antibiotics if a bacterial pneumonia is suspected. This review focuses on practical issues of clinical relevance for the general pediatrician, including what to elicit from the patient history and examination, keeping in mind not only the infections that are commonly seen but also emerging infectious diseases and those that are less frequently seen but that are severe when they occur.
Cause and epidemiology
The first key clinical issue is to diagnose CAP in children, and then determine which pathogen is responsible. There are discrepant definitions of CAP depending on whether the consideration is epidemiologic, which has more sensitive criteria, or regulatory, which is more specific ( Table 1 ). Causative agents in children have been difficult to identify; however, clues in the history may help point toward certain infectious pathogens ( Table 2 ). The cause of pediatric pneumonia is usually based on age, because that is the best predictor available ( Table 3 ).
| World Health Organization |
|
| British Thoracic Society | Persistent or repetitive fever >38.5°C together with chest recession and an increased respiratory rate |
| Infectious Diseases Society of America | Presence of signs and symptoms of pneumonia in a previously healthy child caused by an infection that has been acquired outside the hospital |
| Factor | Possible Agent(s) |
|---|---|
| Host factor | |
| Sickle cell disease | Streptococcus pneumoniae |
| Human immunodeficiency virus infection and CD4+ lymphocyte count of <200/μL | Streptococcus pneumoniae, Haemophilus influenzae, Cryptococcus neoformans, Mycobacterium tuberculosis |
| Structural lung disease (bronchiectasis) | Pseudomonas aeruginosa |
| Travel | |
| Travel to southeast Asia | Burkholderia pseudomallei, Mycobacterium tuberculosis |
| Travel to China, Taiwan, Toronto, Canada, Middle East | Coronavirus causing SARS |
| Travel to tuberculosis-endemic countries | Mycobacterium tuberculosis |
| Travel to desert regions of southwestern United States, and Central and South America | Coccidioides immitis |
| Travel to Ohio and St Lawrence River valleys | Histoplasma capsulatum |
| Travel to Peru | Sporothrix schenckii |
| Travel to Vancouver Island, Canada, and Pacific Northwest (camping, residence) | Cryptococcus gattii |
| Other environmental factors | |
| Pneumonia outbreak in a homeless shelter | Streptococcus pneumoniae, Mycobacterium tuberculosis |
| Lawn mowing in an endemic area, including southcentral and western states and Martha’s Vineyard | Francisella tularensis |
| Exposure to parturient cats, sheep, goats, and cattle in an endemic area, including western and plains states where ranching and rearing of cattle are common | Coxiella burnetii |
| Sleeping in a rose garden, playing on bales of hay | Sporothrix schenckii |
| Exposure to windstorm in an endemic area | Coccidioides immitis, Coxiella burnetii |
| Exposure to bats, excavation or residence in an endemic area | Histoplasma capsulatum |
| Camping, cutting down trees in an endemic area, including the Mississippi River and Ohio River valley basins and around the Great Lakes | Blastomyces dermatitidis |
| Exposure to mouse droppings in an endemic area, including the Four Corners and Yosemite National Park | Hantavirus |
| Immunosuppressed and exposure to hot tub; grocery store mist machine; recent stay in a hotel; visit to or recent stay in a hospital with Legionellaceae-contaminated drinking water | Legionella pneumophila , other Legionellaceae |
| Age Grouping, Cause | Associated Testing |
|---|---|
| Birth–20 d | |
| Group B streptococci | Blood cultures should not be routinely performed in fully immunized, nontoxic children in outpatient setting, but should be obtained if children fail to improve or have progressive symptoms or clinically deteriorate after starting antibiotic therapy; blood and pleural fluid culture are insensitive, but there are no established alternatives in children |
| Gram-negative enteric bacteria | |
| Listeria monocytogenes | |
| 3 wk–3 mo | |
| Chlamydia trachomatis | Quadrupling of acute and convalescent serology, NP culture or NP PCR; although IDSA does not recommend diagnostic testing, because reliable and readily available diagnostic tests do not exist |
| RSV | NP swab for PCR or immunofluorescence, viral culture and DFA staining, acute and convalescent serology. Whereas influenza and RSV have winter-spring seasonality, PIV3 is present year-round |
| PIV 3 | |
| Streptococcus pneumoniae | Blood culture (yield <10%), urinary antigen (low specificity, many false-positives because of NP carriage), pneumolysin-based PCR of blood, pleural fluid and secretions |
| Bordetella pertussis | Culture, immunofluorescence assay, PCR assay of NP secretions |
| Staphylococcus aureus | Blood culture, pleural fluid culture |
| 4 mo–4 y | |
| RSV, parainfluenza viruses, influenza virus, adenovirus, rhinovirus | NP swab for PCR or immunofluorescence, viral culture and DFA staining, acute and convalescent serology |
| Streptococcus pneumoniae | Blood culture (yield <10%), urinary antigen (low specificity, many false-positive results because of NP carriage), pneumolysin-based PCR of blood, pleural fluid and secretions |
| Haemophilus influenzae | Blood culture, pleural fluid culture |
| Mycoplasma pneumoniae | Quadrupling of acute and convalescent serology is diagnostic, IgM antibody in acute or early convalescent serum is helpful, throat or NP swab PCR (high specificity and positive predictive value) |
| Mycobacterium tuberculosis | Identify bacteria in culture of sputum or gastric aspirates, with positive tuberculin skin test or interferon γ release assay |
| 5–15 y | |
| Mycoplasma pneumoniae | Quadrupling of acute and convalescent serology is diagnostic, IgM antibody in acute or early convalescent serum is helpful, throat or NP swab PCR (high specificity and positive predictive value) |
| Chlamydia pneumoniae | Quadrupling of acute and convalescent serology, NP culture or NP PCR; although IDSA does not recommend diagnostic testing, because reliable and readily available diagnostic tests do not exist |
| Streptococcus pneumoniae | Blood culture (yield <10%), urinary antigen (low specificity, many false-positive results because of NP carriage), pneumolysin-based PCR of blood, pleural fluid, and secretions |
| Influenza A or B, adenovirus | NP swab for PCR or immunofluorescence, viral culture and DFA staining, acute and convalescent serology |
| Nontypeable Haemophilus influenzae | Blood culture, pleural fluid culture |
| Mycobacterium tuberculosis | Identify bacteria in culture of sputum or gastric aspirates, with positive tuberculin skin test or interferon γ release assay |
| All ages, severe pneumonia requiring admission to intensive care unit: | |
| Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, Haemophilus influenzae type b, Mycoplasma pneumoniae, adenovirus | |
| Uncommon causes of pediatric CAP: | |
| Viruses: varicella zoster virus, coronaviruses, enteroviruses (coxsackievirus and echovirus), cytomegalovirus, Epstein-Barr virus, mumps virus, herpes simplex virus (in newborns), bocaviruses, polyomaviruses, measles virus, hantavirus | Varicella zoster virus: quadrupling of acute and convalescent serology, immunofluorescent assay of skin secretions; cytomegalovirus, Epstein-Barr virus: quadrupling of acute and convalescent serology, IgM antibody in acute serum; measles virus: quadrupling of acute and convalescent serology, immunofluorescent assay of NP secretions; hantavirus: quadrupling of acute and convalescent serology, IgM antibody in acute serum NP secretions or antibody in serum; sufficiently uncommon that IgM or IgG antibody in serum is essentially diagnostic |
| Chlamydia: Chlamydia psittaci | Quadrupling of acute and convalescent serology is diagnostic |
| Coxiella: Coxiella burnetii | Quadrupling of acute and convalescent serology is diagnostic |
| Bacteria: Streptococcus pyogenes , anaerobic mouth flora ( Streptococcus milleri, Peptostreptococcus ), nontype B (but typeable) Haemophilus influenzae, Bordetella pertussis, Klebsiella pneumoniae, Escherichia coli, Listeria monocytogenes, Neisseria meningitides (often group Y), Legionella, Burkholderia pseudomallei, Francisella tularensis, Brucella abortus, Leptospira | Francisella tularensis: quadrupling of acute and convalescent serology is diagnostic (blood or sputum culture requires special medium and may pose danger of infection to laboratory workers and they should be notified before handling specimen); Legionella pneumophila and other Legionella species: sputum or tracheal aspirate culture, urinary antigen (urinary antigen tests detect only Legionella pneumophila antigen); Brucella abortus: blood culture, quadrupling of acute and convalescent serology |
| Fungi: Coccidioides immitis , Histoplasma capsulatum, Blastomyces dermatitidis | Urinary Histoplasma or Blastomyces antigen, stain or culture of respiratory tract secretions, serum IgM antibody; quadrupling of acute and convalescent serology |
Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) have been characterized as 2 bacteria predominately responsible for cases of fatal pneumonia in children. However, widespread introduction of Hib and pneumococcal conjugate vaccines has led to significant declines, especially of Hib, although Streptococcus pneumoniae is still the predominant bacteria isolated from bacterial CAP in children. There is increasing recognition of the prevalence of mixed bacterial and viral infections, which have been documented in 23% to 33% of cases of pneumonia.
Atypical organisms (eg, Mycoplasma pneumoniae, Chlamydia pneumoniae ) account for up to a third of cases. A new Chlamydia -like organism, Simkania negevensis , has been associated with bronchiolitis and pneumonia in children, and has also been found in healthy, asymptomatic individuals and may be an opportunistic organism rather than a true pathogen.
Viral pathogens are responsible for most clinical disease in younger children, accounting for 77% of clinical pneumonia in children younger than 1 year compared with 59% in those older than 2 years. Viruses account for 30% to 67% of pediatric CAP, with influenza A, respiratory syncytial virus (RSV), and parainfluenza virus (PIV) 1, 2, and 3 most commonly identified. A study by Singleton and colleagues recovered respiratory viruses from 90% of Alaskan children younger than 3 years hospitalized with respiratory infections. In that case-control study of 865 children, RSV, PIV, human metapneumovirus (hMPV), and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not.
The high occurrence of asymptomatic carriage, such as in up to a third of asymptomatic children harboring rhinovirus, complicates the frequent detection of these respiratory viruses ; the causative nature of many respiratory viruses in pneumonia, particularly ones identified by sensitive new molecular diagnostics, remain unclear. However, rhinovirus identification has been associated with bronchiolitis, asthma, and wheezing. hMPV, isolated in 2001, has been recovered in 3.8% to 8.3% of isolates of nasopharyngeal and throat specimens of hospitalized children or children with CAP. Human bocavirus, first described in 2005, has been detected in up to 19% of clinical samples, mainly in infants and young children ; its detection in serum and stool suggests that the virus may cause systemic disease. In 2007, WU and KI polyomaviruses were detected in the respiratory tract samples of adults and children, and subsequently shown to be present in respiratory secretions in patients with acute respiratory illness.
Severe acquired respiratory syndrome (SARS)-associated coronavirus was the first novel coronavirus to be characterized among a succession of other novel coronaviruses that decade. Using sensitive reverse transcription polymerase chain reaction (PCR) assays, Dominguez and colleagues detected coronavirus RNAs in 5% of pediatric respiratory specimens, and 41% of coronavirus-positive patients had evidence of a lower respiratory tract infection. Twenty-six percent of that group presented with vomiting or diarrhea, and 8% with meningoencephalitis or seizures, which suggests that coronavirus may have more systemic involvement than previously believed.
Fungal pathogens such as Histoplasma, Coccidioides, Blastomyces, and Cryptococcus can cause pneumonia the immunocompromised patient population and may cause clinical illness in immunocompetent hosts, but usually not with the presentation of CAP. Blastomyces can cause prolonged fever and respiratory symptoms that mimic a prolonged CAP; however. Cryptococcus gattii, which can infect immunocompetent hosts, has caused an increasing number of infections in the US Pacific Northwest since 2004 and has been detected in the southeastern United States. The pathogen can cause cryptococcomas in the lungs, and in 1 report, 54% of infected patients had documented pneumonia. Mycobacterium tuberculosis and nontuberculous mycobacteria can likewise cause CAP, but tend to be limited to people with high-risk exposures. Similarly, other high-risk exposures suggest specific causes, as outlined in Table 2 .
Patient history
Symptoms (fever, chills, cough) of pneumonia can overlap significantly with a spectrum of conditions, such as bacterial sepsis or severe anemia, making differentiation between these diagnoses challenging. Signs such as crackles and egophony are more specific, but are often absent in clinical pneumonia in children. Chest radiography is considered the gold standard for confirmation of pneumonia, but is also of questionable benefit in children, as discussed later. The limitation in diagnosis is reflected in the various definitions of pediatric CAP that exist (see Table 1 ), none of which is considered sufficiently sensitive or specific, and few of which have been validated in children. For example, the World Health Organization (WHO) criteria for mild to moderate CAP are based on cough or breathing difficulties and age-adjusted tachypnea; such a definition places CAP with all other types of lower respiratory tract disease.
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