Community-Acquired Pneumonia in Children (aged older than 3 months)

Terminology

Clinical Clarification

• Community-acquired pneumonia is an acute infection of the pulmonary parenchyma that occurs in a child who has not resided in a hospital or health care facility in the preceding 14 days

Classification

• By cause

  • Typical versus atypical

    • Terms coined in the 1930s when diagnostic tests were limited and 90% of cases of community acquired pneumonia were caused by Streptococcus pneumoniae ^[2]

      • Typical presentation characterized by an abrupt onset of fever and shaking chills, cough, pleurisy, and lobar consolidation on chest radiograph

      • Other bacteria that cause pneumonia with a typical presentation include Haemophilus influenzae, Staphylococcus aureus, group A streptococci_, Moraxella catarrhalis,_ anaerobes, and aerobic gram-negative bacteria

  • Atypical pneumonia ^[2]

    • Caused by other infectious agents that present more gradually and exhibit more systemic symptoms (headache, myalgias), with cough and low- grade fever without chills

    • Atypical causes of community-acquired pneumonia include Mycoplasma pneu moniae, Chlamydia pneumoniae, Chlamydia psittaci, Legionella species, Coxiella burnetii, fungi, protozoa, and the respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, adenovirus, measles, COVID-19, SARS, Middle East respiratory syndrome [virus])

  • In practice it is difficult to distinguish atypical from typical pneumonia on the basis of clinical or radiographic features ^[2]

• By severity and site of care

  • Pneumonia that can be managed on an outpatient basis ^[1]

  • Moderate to severe community-acquired pneumonia, as defined by respiratory distress and/or hypoxemia, that should be managed with general ward admission ^[1]

    • Respiratory distress

      • Tachypnea, retractions, grunting, and nasal flaring

      • Apnea

      • Altered mental status

    • Hypoxemia

      • Pulse oximetry measurement less than 90% on room air

  • Severe pneumonia that meets at least 1 major or 2 minor severity criteria that require ICU admission (from Pediatric Infectious Diseases Society-Infectious Diseases Society of America) ^[1]

    • Major criteria

      • Need for invasive mechanical ventilation

      • Fluid refractory shock

      • Acute need for noninvasive positive pressure ventilation

      • Hypoxemia requiring FiO₂ (fraction of inspired oxygen) greater than inspired concentration or flow feasible in general care area

    • Minor criteria

      • Respiratory rate higher than WHO classification for age

      • Apnea

      • Increased work of breathing (eg, retractions, dyspnea, nasal flaring, grunting)

      • PaO₂ to FiO₂ ratio less than 250

      • Multilobar infiltrates

      • Pediatric Early Warning score (bedside nursing assessment tool based on vital signs and neurologic examination) greater than 6 ^[3]

      • Altered mental status

      • Hypotension

      • Presence of effusion

      • Comorbid conditions (eg, sickle cell anemia, immunosuppression, immunodeficiency)

      • Unexplained metabolic acidosis

    • A validation study of these criteria found them to be sensitive, but with poor specificity; over half of children classified as having severe community-acquired pneumonia did not require hospital admission ^[4]

Diagnosis

Clinical Presentation

History

• Common symptoms

  • Fever

  • Cough

  • Respiratory distress (eg, tachypnea, nasal flaring, grunting, retractions)

  • Poor feeding

  • Irritability

• Less common symptoms

  • Abdominal pain

  • Nausea or vomiting

  • Chest pain

• Headache and/or sore throat are common in children presenting with SARS-CoV-2 infection ^[5][6]

• Receipt of conjugate pneumococcal vaccine decreases probability of bacterial pneumonia ^[7]

Physical examination

• Fever

• Tachypnea alone is a sensitive sign of pneumonia ^[8]

  • Age 2 to 12 months: more than 50 breaths per minute ^[1]

  • Age 1 to 5 years: more than 40 breaths per minute ^[1]

  • Older than 5 years: more than 20 breaths per minute ^[1]

  • Less sensitive in early illness (within first 3 days) ^[8]

• Nasal flaring, retractions, and reduced oxygen saturation increase likelihood of pneumonia diagnosis

• Abnormal lung examination findings

  • Localized rales on auscultation in younger children

  • Rales, bronchial breathing, and pleural rub on auscultation in older children

  • Wheezing more commonly associated with atypical or viral pneumonia

  • Absent breath sounds and dull percussion raise concern for an effusion ^[7]

Causes and Risk Factors

Causes

• Most common, by age group

  • Neonatal

    • Bacterial ^[9]

      • Group B streptococci

      • Listeria monocytogenes

      • Gram-negative bacilli

      • Chlamydia trachomatis

  • Children older than 1 month

    • Viral (up to 70% of cases) ^[9]

      • Human respiratory syncytial virus (more common among children younger than 5 years) ^[10]

      • Parainfluenza viruses 1, 2, and 3

      • Influenza A and B viruses

      • SARS-CoV-2

        • Limited data suggest that SARS-CoV-2 is responsible for up to 20% of community-acquired pneumonia cases among children requiring hospital admission during pandemic conditions ^[5]

      • Human adenovirus (more common among children younger than 5 years) ^[10]

      • Human rhinovirus

      • Human herpesviruses 1 and 2

      • Human metapneumovirus (more common among children younger than 5 years) ^[10]

      • Human enterovirus

    • Bacterial ^[9]

      • Streptococcus pneumoniae (routine childhood vaccination has led to reduced incidence)

      • Haemophilus influenzae type b (routine childhood vaccination has led to reduced incidence)

      • Moraxella catarrhalis

      • Staphylococcus aureus

      • Mycoplasma pneumoniae (more common among older children and adolescents)

      • Chlamydia pneumoniae (more common among older children and adolescents)

Risk factors and/or associations

Age

• Highest incidence among children younger than 2 years ^[10]

• Higher incidence among premature infants ^[11]

Sex

• Male children have higher incidence at all ages ^[11]

Other risk factors/associations

• Chronic respiratory conditions leading to infection (eg, cystic fibrosis, bronchiectasis)

• Immune deficiency

• Chronic lung disease of prematurity

• Congenital heart disease

• Use of gastric acid inhibitors ^[12]

• Risk factors in resource-limited countries: ^[13]

  • Definite risk factors

    • Malnutrition

    • Low birth weight (2500 g or less)

    • Nonexclusive breastfeeding (especially during first 4 months of life)

    • Lack of measles immunization within first 12 months of life

    • Indoor air pollution

    • Crowding

    • Lack of proper sanitation, clean water, and handwashing ^[14]

  • Likely risk factors

    • Parental smoking

    • Zinc deficiency

    • Other coexisting diseases (eg, diarrhea, heart disease, asthma)

Diagnostic Procedures

Primary diagnostic tools

• History and physical examination are primary diagnostic tools

  • WHO criteria for pneumonia require only findings of cough and tachypnea on physical examination ^[13]

    • WHO definition of tachypnea

      • Age 2 to 12 months: more than 50 breaths per minute

      • Age 1 to 5 years: more than 40 breaths per minute

  • Perform pulse oximetry for all children with suspected hypoxemia

• Suspected or probable infection with SARS-CoV-2

  • Implement early and strict transmission-based precautions using contact, respiratory droplet, and airborne precautions during aerosol-generating procedures

  • Chest imaging is not usually necessary for most children with lower respiratory tract infection with SARS-CoV-2 because imaging does not often change clinical management and poses risk to infection control measures ^[15]

  • Confirm SARS-CoV-2 infection with nucleic acid amplification test or antigen test performed on respiratory specimen ^[16]

• Additional testing for patients admitted to hospital (those meeting requirements for moderate to severe pneumonia)

  • Chest radiograph

  • Blood and sputum cultures

  • Viral pathogen testing

  • Testing for Mycoplasma infection (if suspected)

  • CBC

  • Acute phase reactants (eg, erythrocyte sedimentation rate, C-reactive protein, serum procalcitonin concentration) may be helpful for some patients

Laboratory

• Blood cultures

  • Obtain if child has probable bacterial pneumonia that is moderate to severe, associated with complications, or requires admission ^[1]

  • Not routinely needed for children with community-acquired pneumonia who have nontoxic appearance, are fully immunized, and are being treated in outpatient setting ^[1]

    • Obtain if child deteriorates or symptoms worsen after antibiotics are started ^[1]

• Sputum culture

  • Obtain culture and Gram stain for children who are hospitalized and can produce sputum ^[1]

• Tracheal aspirates ^[1]

  • Obtain if child requires endotracheal intubation

    • Gram stain and culture

    • Viral pathogens, including influenza virus

• Viral pathogen testing

  • Obtain select studies for specific pathogens in hospitalized patients as clinically indicated for isolation measures and when treatment may be affected for certain pathogens (eg, influenza viruses, SARS-CoV-2 )^[17][16]

  • Use sensitive and specific tests for rapid diagnosis of influenza virus, SARS-CoV-2, and other respiratory viruses

    • Influenza viruses

      • Positive influenza virus test result reduces additional diagnostic studies and antibiotic use, and it guides use of antiviral agents ^[1]

      • Initial negative test results, especially from rapid antigen tests, do not exclude influenza viruses ^[1]

    • SARS-CoV-2

      • Confirm infection with detection of either viral nucleic acid (nucleic acid amplification test) or protein (antigen test) on respiratory specimen ^[16]

• Atypical bacterial testing

  • Polymerase chain reaction

    • If suspicion exists for Mycoplasma pneumoniae, a variety of diagnostic tests are available, but polymerase chain reaction is most rapid and accurate method ^[1][18]

    • Testing for Chlamydia pneumoniae is not recommended ^[1]

• CBC

  • Obtain for hospitalized patients ^[1]

• Acute phase reactants (eg, erythrocyte sedimentation rate, C-reactive protein concentration, serum procalcitonin concentration)

  • No need to measure routinely for fully immunized children with community-acquired pneumonia who will be treated as outpatients but may be helpful to measure for children with more serious disease or complications ^[1]

    • May help in monitoring response to therapy and course of disease

    • May help distinguish between bacterial and viral disease but should not be sole criteria used ^[1]

      • Elevated levels of procalcitonin are associated with greater likelihood of bacterial cause for pneumonia; however, predictive thresholds are not well established ^[19]

      • Low levels of procalcitonin help exclude bacterial pneumonia ^[19]

        • In the CDC EPIC trial, none of the 120 children with very low procalcitonin levels (less than 0.1 nanograms/mL) had typical bacteria detected, and only 3.6% with low procalcitonin levels (less than 0.25 nanograms/mL) had typical bacteria detected

Imaging

• Chest radiography

  • Not necessary for patients with suspected community-acquired pneumonia with mild symptoms who do not require admission ^[1][20]

  • Use posteroanterior and lateral radiographic views for patients with hypoxemia, respiratory distress, or other indications for hospitalization and for patients who do not respond to initial outpatient antibiotic therapy ^[1][20]

    • British Thoracic Society guidelines do not advocate for routine lateral films ^[7]

  • Lobar consolidation is typically seen in pneumococcal pneumonia

  • Hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing is seen in most instances of viral pneumonia

  • Findings in patients with COVID-19 pneumonia

    • Common findings include unilateral focal consolidation or bilateral patchy pulmonary infiltrates ^[16]

    • Pleural effusions are rare and findings frequently noted in other lower viral respiratory tract infections are uncommon (eg, increased perihilar markings, hyperinflation) ^[21]

  • Repeat chest radiography for children who do not improve, have worsening of symptoms, or have clinical deterioration within 48 to 72 hours of starting antibiotic therapy

• Lung ultrasonography

  • Indicated as first line imaging for patients with complicated pneumonia ^[20][22]

    • Valuable for diagnosis and assessment of pleural effusions

  • Evidence supports lung ultrasonography (which does not require radiation exposure) as alternative to chest radiography for initial diagnosis of pneumonia in children ^[23][24][25]

• Chest CT

  • Reserve chest CT for complicated pneumonia cases in which chest ultrasonography is technically limited or discrepant with clinical findings ^[22]

  • Indicated for investigation of suspected bronchopleural fistula, lung abscess, or recurrent pneumonia ^[20]

Functional testing

• Pulse oximetry

  • Perform for all children with pneumonia and suspected hypoxemia

    • Hypoxemia guides admission and discharge decisions and need for further diagnostic evaluation ^[1]

Differential Diagnosis

Most common

• Bronchitis

  • Occurs in older adolescents; acute bronchitis is not usually diagnosed in young children

  • Afebrile or low-grade fever (lower than 38 °C), malaise, chest pain, and protracted dry, hacking cough (which may be productive) lasting for 1 to 3 weeks

  • Chest radiographs usually show no abnormalities or may have increased bronchial markings

  • Absence of tachycardia, tachypnea, and high fever helps to differentiate from pneumonia

• Bronchiolitis

  • Acute infection of lower respiratory tract resulting in small airway obstruction

  • Respiratory syncytial virus is most common cause of bronchiolitis in children younger than 2 years and can be confirmed with rapid viral antigen or polymerase chain reaction, but diagnosis is clinical

  • Commonly occurs in infants aged 1 to 3 months, with peak incidence during winter and early spring

  • Usually starts with sneezing and clear rhinorrhea; fine crackles or overt wheezes with prolongation of expiratory phase of breathing can be heard on auscultation

  • Chest radiographs may show hyperinflated lungs with patchy atelectasis

• COVID-19

  • Spectrum of illness caused by SARS-CoV-2 is quite variable

    • Most children exhibit either asymptomatic or mild disease; when symptomatic, most common manifestations are fever, cough, and sore throat

    • Common presenting syndromes include acute respiratory tract infection; asthma exacerbation; influenzalike illness; isolated fever, gastroenteritis, and vomiting; and community-acquired pneumonia

    • Up to about 40% of children develop moderate disease (eg, evidence of lower airway disease by clinical assessment or imaging without hypoxia), about 2% develop severe illness (eg, lower airway disease with hypoxia), and about 0.7% develop critical illness (eg, shock, respiratory failure, multiple organ failure) ^[26]

  • May have known exposure to confirmed case (typically within own household)

  • Infection with respiratory pathogens other than SARS-CoV-2 (eg, influenza, respiratory syncytial virus, Mycoplasma pneumoniae) does not exclude diagnosis because coinfection with additional respiratory pathogens occurs in up to 6% ^[27]

  • Findings may be present on chest imaging before symptoms manifest; approximately 44% of children with COVID-19 in 1 systematic review data set show evidence of radiographic abnormalities on chest radiograph or chest CT ^[28]

    • Chest imaging ^[21]

      • May reveal unilateral or bilateral pulmonary infiltrates

      • Pleural effusions are rare

      • Findings frequently noted in other lower viral respiratory tract infections are uncommon (eg, increased perihilar markings, hyperinflation)

  • Diagnosis is confirmed by rapid antigen or polymerase chain reaction for SARS-CoV-2 on specimens from upper respiratory tract ^[29]

• Pertussis (whooping cough)

  • Symptoms occur in 3 phases:

    • Catarrhal

      • Low-grade fever, upper respiratory tract infection symptoms, and cough

      • Apnea may occur

    • Paroxysmal

      • Coughing episodes; whoop occurs in older children

      • Vomiting

      • Infants typically do not produce whoop but have paroxysmal cough and/or apnea with color change

    • Convalescent

      • Persistent cough

  • Differentiate by cough history and polymerase chain reaction

• Asthma

  • Symptoms include episodic dry cough, expiratory wheezing, chest tightness, feeling of discomfort in chest, and shortness of breath in response to physical exertion or airway irritants

  • Severe exacerbations are associated with inspiratory and expiratory wheezing, retractions, nasal flaring, and use of accessory respiratory muscles

  • Dyspnea is present, but signs of infection are usually absent

  • Airway obstruction reversible with bronchodilators in setting of clear chest radiograph is diagnostic

• Tuberculosis

  • Suspect when child is from endemic area or has had contact with persons who are at high risk of having the disease, including those who are urban homeless, are incarcerated, and have HIV infection

  • Presents subacutely with anorexia, weight loss, and night sweats

  • Differentiate based on history of either being from endemic area or having exposure to high-risk people

• Acute respiratory distress syndrome

  • Mild respiratory distress with tachypnea, dyspnea, and increased oxygen requirement progresses rapidly to severe hypoxia accompanied by carbon dioxide retention and respiratory failure

  • Chest radiograph may reveal interstitial and alveolar pulmonary edema

  • Patients with measured PaO₂ to percentage of FiO₂ (fraction of inspired oxygen) ratio of less than 200 are considered to have severe hypoxia and are classified as having acute respiratory distress syndrome

Treatment

Goals

• Reduce respiratory symptoms

• Eradicate infection with antimicrobials, if indicated

• Prevent complications

Disposition

Admission criteria

Respiratory distress ^[1]

• Tachypnea

  • Age 0 to 2 months: more than 60 breaths per minute

  • Age 2 to 12 months: more than 50 breaths per minute

  • Age 1 to 5 years: more than 40 breaths per minute

  • Older than 5 years: more than 20 breaths per minute

• Retractions (ie, suprasternal, intercostals, subcostal)

• Grunting

• Nasal flaring

• Apnea

• Altered mental status

Hypoxemia (defined by pediatric pneumonia guidelines as sustained oxygen saturation less than 90% on room air) ^[1]

Age younger than 6 months and suspected bacterial community-acquired pneumonia ^[1]

Suspected or documented community-acquired pneumonia caused by potentially virulent pathogen (eg, community-associated MRSA) ^[1]

Moderate (clinical or radiographic evidence of lower airway disease without hypoxia) or severe COVID-19 disease (hypoxia, more than 50% lung infiltrates, significant tachypnea, or severe respiratory distress)

Concern about observation at home, inability to comply with therapy, or unavailability for follow-up ^[1]

Criteria for ICU admission

• Need for noninvasive positive pressure ventilation or endotracheal intubation ^[1]

• Impending respiratory failure ^[1]

• Sustained tachycardia, hypotension, or need for pharmacologic support of blood pressure or perfusion ^[1]

• Inspired oxygen greater than 50% results in pulse oximetry measurement of 92% or less ^[1]

• Altered mental status due to hypercarbia or hypoxemia resulting from pneumonia ^[1]

• Do not use severity of illness scores as only criteria for ICU admission; use them in context of other clinical, laboratory, and radiologic findings ^[1]

Recommendations for specialist referral

• Refer to pediatric infectious disease specialist for:

  • Age younger than 6 months

  • No improvement while receiving antibiotics

  • Recurrent or complicated pneumonia

• Refer to pediatric surgeon for:

  • Pleural effusion

Treatment Options

Empiric antibiotic therapy ^[1]

• Prescribe empiric antibiotic therapy according to age and care setting; typical duration is 5 to 7 days ^{[9][30][31][32]}

  • Shorter courses may be equally effective for mild illness managed on outpatient basis ^[1]

    • Meta-analysis of studies using high-dose amoxicillin or amoxicillin-clavulanic acid for outpatient treatment of pediatric community-acquired pneumonia in high-income countries found no difference in failure rate between 3 to 5 day and 7 to 10 day treatment courses ^[33]

    • The SAFER trial demonstrated that 5 days of therapy was comparable to longer courses in previously healthy children not requiring hospitalization ^[32]

    • The SCOUT-CAP trial found that 5 days of treatment was superior to 10 days for outpatient therapy ^[30]

    • Single-center comparative effectiveness study of hospitalized children aged 6 months and older found a 5 to 7 day course did not increase the odds of 30-day treatment failure compared with longer courses (eg, 8 to 14 days) ^[31]

    • Shorter courses of antibiotics may be associated with reduced development of antibiotic-resistant bacteria ^[34]

  • Investigate further if deterioration or failure to improve occurs after 48 to 72 hours of antibiotic therapy ^[9]

• Outpatient ^[1]

  • Older than 3 months to younger than 5 years

    • Antimicrobial therapy not routinely required for preschool-aged children with community-acquired pneumonia because majority of cases are viral

    • Amoxicillin is first line therapy for appropriately immunized infants or preschool-aged children with suspected typical bacterial community-acquired pneumonia

    • Azithromycin is first line therapy for children with community-acquired pneumonia suspected to be caused by atypical organisms

  • Age 5 to 17 years

    • Amoxicillin is first line therapy for appropriately immunized school-aged children and adolescents with suspected typical bacterial community-acquired pneumonia

      • Combination therapy with a macrolide in addition to a β-lactam antibiotic can be prescribed if no features to distinguish bacterial from atypical pneumonia are present

    • Azithromycin is first line therapy for children with community-acquired pneumonia suspected to be caused by atypical organisms

• Inpatient (older than 3 months) ^[1]

  • Ampicillin or penicillin G is first line therapy for fully immunized infant or school-aged child admitted to hospital ward with community-acquired pneumonia when no local substantial high-level penicillin resistance for invasive Streptococcus pneumoniae is present

  • Third-generation parenteral cephalosporin (eg, ceftriaxone, cefotaxime) is first line therapy for hospitalized infants and children who are not fully immunized, in regions where invasive pneumococcal strains show high-level penicillin resistance (minimum inhibitory concentrations 4.0 mcg/mL or higher), and for infants and children with life-threatening infection, including those with empyema

    • Consider adding vancomycin for children with potential resistant or life-threatening infection

  • Add antistaphylococcal coverage (eg, clindamycin or vancomycin) if MRSA is suspected

    • Consider Staphylococcus aureus superinfection in patients with influenza

  • Add a macrolide (oral or parenteral) in addition to a β-lactam antibiotic if atypical organisms are significant considerations

    • However, empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia in prospective study, including subset of children with confirmed atypical bacteria ^[35]

Pathogen-directed therapy ^[1]

• Adjust antibiotic therapy, if necessary, based on culture results ^[1]

• Recommended antibiotic regimens for specific pathogens are available in clinical practice guidelines by Pediatric Infectious Diseases Society and Infectious Diseases Society of America ^[1]

Influenza antiviral therapy ^[1]

• Indicated for children of any age hospitalized with suspected or confirmed influenza-induced community-acquired pneumonia regardless of duration of symptoms ^[36]

  • Also offer to outpatients with severe, complicated, or progressively worsening illness attributable to influenza and those at high risk for complications due to influenza ^[36]

• Start treatment as soon as possible; however, even after 48 hours of symptomatic infection treatment, may still provide clinical benefit to those with more severe disease ^[1]

  • Do not delay treatment in case of positive influenza test results ^[1]

• Options include oseltamivir, zanamivir, baloxavir, and peramivir ^[36]

  • Oseltamivir is the preferred agent of the American Academy of Pediatrics based on cumulative experience, cost, and ease of administration

• Consult CDC Influenza Surveillance Report for recent drug resistance information to aid drug selection ^[37]

COVID-19 therapy

• Treat in accordance with hospital isolation policy and standard transmission-based precautions; minimum includes strict contact, respiratory droplet, and airborne precautions during aerosol-generating procedures

• NIH classifies patients to be at high risk for progression to severe COVID-19 in the following circumstances: ^[38]

  • Moderate or severe immunocompromise (vaccination status irrelevant)

  • Unvaccinated patients with any one of the following conditions:

    • Obesity (BMI at or above the 95th percentile for age)

    • Medical complexity with dependence on respiratory technology

    • Severe disability that results in impaired airway clearance or self-care

    • Severe asthma or other chronic lung disease

    • Severe cardiac disease

    • Multiple moderate to severe chronic diseases

• Ritonavir-boosted nirmatrelvir (Paxlovid) ^[38]

  • Available under emergency use authorization for children 12 years and older weighing 40 kg or more

  • Only oral antiviral agent available for children

  • Has significant drug-drug interactions

  • Recommended for the following:

    • Nonhospitalized children aged 12 years or older with mild to moderate COVID-19 at high risk for progression to severe COVID-19, within 5 days of disease onset

• Remdesivir

  • FDA approved for use in nonhospitalized and hospitalized pediatric patients aged 28 days or older and weighing 3 kg or more ^[38]

  • Recommended for the following populations based on criteria:

    • Nonhospitalized children ^[38]

      • Children aged 12 years or older with mild to moderate COVID-19 at high risk for progression to severe COVID-19

        • As an alternative to ritonavir-boosted nirmatrelvir ^[38]

      • Initiate therapy within 7 days of symptom onset

      • NIH found insufficient evidence to recommend either for or against routine use in nonhospitalized children younger than 12 years with mild to moderate COVID-19 at high risk for progression to severe COVID-19; consider treatment based on age and other risk factors ^[38]

    • Children hospitalized for COVID-19 ^[39]

      • Children aged 12 years or older not requiring oxygen but at high risk for progression to severe COVID-19 ^[39]

        • There is insufficient evidence for children between the ages of 28 days and 12 years

      • All children requiring conventional oxygen ^[39]

      • All children requiring oxygen through high-flow device or noninvasive ventilation ^[39]

        • As additional therapy to dexamethasone

      • Greatest clinical benefit if initiated within 10 days of symptom onset

• Dexamethasone

  • Corticosteroids are not indicated for nonhospitalized children with COVID-19 ^[38]

    • Children with asthma or croup triggered by COVID-19 should receive corticosteroids per usual standards of care

    • Children with COVID-19 receiving steroids for an underlying condition should continue this therapy as directed by their health care professionals

  • Recommended for hospitalized pediatric patients with COVID-19 who require any of the following: ^[39]

    • Increasing supplemental oxygen

    • High-flow oxygen

    • Noninvasive or invasive ventilation

    • Extracorporeal membrane oxygenation

  • Consider addition of dexamethasone for increasing oxygen needs, especially for adolescents ^[39]

• Children who do not demonstrate improvement in oxygenation within 24 hours of starting dexamethasone can be considered for the immunosuppressant drugs baricitinib, tofacitinib, or tocilizumab in consultation with an infectious disease specialist ^[39]

Drug therapy

• Antibiotics

  • Penicillins

    • Oral dosage

      • Amoxicillin

        • Amoxicillin Trihydrate Oral suspension; Infants and Children 4 months to 12 years: 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 5 to 7 days.

        • Amoxicillin Trihydrate Oral capsule; Adolescents: 90 mg/kg/day (Max: 4 g/day) PO divided every 8 to 12 hours for 5 to 7 days.

    • IV dosage

      • Ampicillin

        • Empiric therapy

          • Ampicillin Sodium Solution for injection; Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 8 g/day) IV/IM divided every 6 hours for 5 to 7 days.

        • For resistant strains of Streptococcus pneumoniae (penicillin minimum inhibitory concentration 4 mcg/mL or higher)

          • Ampicillin Sodium Solution for injection; Infants, Children, and Adolescents: 300 to 400 mg/kg/day (Max: 8 g/day) IV/IM divided every 6 hours for 5 to 7 days.

      • Penicillin G

        • Penicillin G Sodium Solution for injection; Infants, Children, and Adolescents: 100,000 to 250,000 units/kg/day IV/IM divided every 4 to 6 hours for 5 to 7 days.

  • Cephalosporins

    • Ceftriaxone

      • Ceftriaxone Sodium Solution for injection; Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) IV/IM divided every 12 to 24 hours for 5 to 7 days.

    • Cefotaxime

      • Cefotaxime Sodium Solution for injection; Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 5 to 7 days.

  • Macrolides

    • Azithromycin

      • Oral dosage

        • Azithromycin Oral suspension; Infants 1 to 5 months†: 10 mg/kg/dose PO for 1 day, followed by 5 mg/kg/dose PO once daily for 4 days.

        • Azithromycin Oral suspension; Infants and Children 6 months to 12 years: 10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

        • Azithromycin Oral tablet; Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO for 1 day, followed by 5 mg/kg/dose (Max: 250 mg/dose) PO once daily for 4 days.

      • IV dosage

        • Azithromycin Solution for injection; Infants, Children, and Adolescents 4 months to 15 years†: 10 mg/kg/dose (Max: 500 mg/dose) IV once daily for 2 days, followed by oral therapy to complete a 5-day treatment course.

        • Azithromycin Solution for injection; Adolescents 16 to 17 years: 500 mg IV once daily for at least 2 days, followed by oral therapy to complete a 5-day treatment course.

    • Clarithromycin

      • Clarithromycin Oral suspension; Infants 1 to 5 months†: 7.5 mg/kg/dose PO every 12 hours for 5 to 7 days.

      • Clarithromycin Oral suspension; Infants, Children, and Adolescents 6 months to 17 years: 7.5 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 5 to 7 days.

    • Erythromycin

      • Erythromycin Lactobionate Solution for injection; Infants, Children, and Adolescents: 20 mg/kg/day (Max: 4 g/day) IV divided every 6 hours for 5 to 7 days.

• Glycopeptide

  • Vancomycin

    • Vancomycin Hydrochloride Solution for injection; Infants and Children 3 months to 11 years: 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day) for at least 7 days; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients.

    • Vancomycin Hydrochloride Solution for injection; Obese Infants and Children 3 months to 11 years: 20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day) for at least 7 days; adjust dose based on target PK/PD parameter.

    • Vancomycin Hydrochloride Solution for injection; Children and Adolescents 12 to 17 years: 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day) for at least 7 days; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients.

    • Vancomycin Hydrochloride Solution for injection; Obese Children and Adolescents 12 to 17 years: 20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day) for at least 7 days; adjust dose based on target PK/PD parameter.

• Lincosamide

  • Clindamycin

    • Oral

      • Clindamycin Palmitate Hydrochloride Oral solution; Infants, Children, and Adolescents: 40 mg/kg/day (Max: 1,800 mg/day) PO divided every 6 to 8 hours for 5 to 7 days.

    • Intravenous

      • Clindamycin Solution for injection; Infants, Children, and Adolescents: 40 mg/kg/day (Max: 1,800 mg/day) IV divided every 6 to 8 hours for 5 to 7 days.

• Antivirals

  • For the treatment of influenza

    • Oseltamivir

      • Oseltamivir Phosphate Oral suspension; Infants 1 to 8 months: 3 mg/kg/dose PO twice daily for 5 days.

      • Oseltamivir Phosphate Oral suspension; Infants 9 to 11 months: 3.5 mg/kg/dose PO twice daily for 5 days.

      • Oseltamivir Phosphate Oral suspension; Children weighing 15 kg or less: 30 mg PO twice daily for 5 days.

      • Oseltamivir Phosphate Oral suspension; Children weighing 16 to 23 kg: 45 mg PO twice daily for 5 days.

      • Oseltamivir Phosphate Oral suspension; Children weighing 24 to 40 kg: 60 mg PO twice daily for 5 days.

      • Oseltamivir Phosphate Oral suspension; Children and Adolescents weighing more than 40 kg: 75 mg PO twice daily for 5 days.

    • Baloxavir

      • Baloxavir Marboxil Oral suspension; Children 5 to 12 years weighing less than 20 kg: 2 mg/kg PO as a single dose.

      • Baloxavir Marboxil Oral suspension; Children and Adolescents 5 to 17 years weighing 20 to 79 kg: 40 mg PO as a single dose.

      • Baloxavir Marboxil Oral suspension; Children and Adolescents 5 to 17 years weighing 80 kg or more: 80 mg PO as a single dose.

    • Zanamivir

      • Zanamivir Inhalation powder; Children and Adolescents 7 to 17 years: 10 mg by oral inhalation every 12 hours for 5 days. Administer 2 doses on the first day provided there are at least 2 hours between doses.

    • Peramivir

      • For the treatment of uncomplicated acute influenza (eg, influenza A virus infection or influenza B virus infection)

        • Peramivir Solution for injection; Infants and Children 6 months to 12 years: 12 mg/kg/dose (Max: 600 mg/dose) IV as a single dose.

        • Peramivir Solution for injection; Adolescents: 600 mg IV as a single dose.

      • For the treatment of novel influenza A viruses associated with severe human disease, including avian influenza A virus infection

        • Peramivir Solution for injection; Children 2 to 12 years who are outpatients with uncomplicated, mild-to-moderate illness: 12 mg/kg (Max: 600 mg) IV as a single dose.

        • Peramivir Solution for injection; Hospitalized children 2 to 12 years who are unable to tolerate or absorb oseltamivir: 12 mg/kg/dose (Max: 600 mg/dose) IV once daily for 5 days. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.

        • Peramivir Solution for injection; Adolescent outpatients with uncomplicated, mild-to-moderate illness: 600 mg IV as a single dose.

        • Peramivir Solution for injection; Hospitalized adolescents who are unable to tolerate or absorb oseltamivir: 600 mg IV once daily for 5 days. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients.

  • Nirmatrelvir/Ritonavir

    • Nirmatrelvir Oral tablet, Ritonavir Oral tablet; Children and Adolescents 12 to 17 years weighing 40 kg or more†: 300 mg nirmatrelvir and 100 mg ritonavir PO twice daily for 5 days.

    • Nirmatrelvir Oral tablet, Ritonavir Oral tablet; Children and Adolescents 12 to 17 years weighing 40 kg or more†: 300 mg nirmatrelvir and 100 mg ritonavir PO twice daily for 5 days.

  • For the treatment of COVID-19

    • Remdesivir

      • For hospitalized patients requiring invasive mechanical ventilation or extracorporeal membrane oxygenation

        • Remdesivir Solution for injection; Infants weighing 3 kg or more: 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 9 days.

        • Remdesivir Solution for injection; Children and Adolescents: 5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 9 days.

      • For hospitalized patients not requiring invasive mechanical ventilation or extracorporeal membrane oxygenation

        • Remdesivir Solution for injection; Infants weighing 3 kg or more: 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 4 days; may extend treatment for up to 5 additional days if no clinical improvement.

        • Remdesivir Solution for injection; Children and Adolescents: 5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 4 days; may extend treatment for up to 5 additional days if no clinical improvement.

      • For the treatment of nonhospitalized patients with mild to moderate COVID-19 who are at high risk for progression

        • Remdesivir Solution for injection; Infants weighing 3 kg or more: 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 2 days.

        • Remdesivir Solution for injection; Children and Adolescents: 5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 2 days.

• Corticosteroids

  • For the treatment of COVID-19

    • Dexamethasone

      • For hospitalized patients requiring high-flow oxygen, noninvasive or invasive mechanical ventilation, or ECMO

        • IV

          • Dexamethasone Sodium Phosphate Solution for injection; Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) IV once daily for up to 10 days.

        • Oral

          • Dexamethasone Oral solution; Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) PO once daily for up to 10 days.

Nondrug and supportive care

IV fluids

• Indicated for patients who are unable to tolerate oral fluids, have oxygen requirement, or have moderate to severe disease

Supplemental oxygen

• Indicated for patients with pulse oximetry readings lower than 90% ^[1]

Procedures

Noninvasive positive pressure ventilation

General explanation

• Delivery of mechanical respiratory support without use of endotracheal intubation ^[40]

• Goal of ventilatory support is to unload work of respiratory muscles, increase ventilation, and thus reduce dyspnea and respiratory rate and improve gas exchange

Indication

• When FiO₂ (fraction of inspired oxygen) greater than 0.5 is necessary to maintain adequate oxygenation

Contraindications

• Best predictive factors for noninvasive positive pressure ventilation failure within setting of acute respiratory failure appear to be level of FiO₂ (greater than 0.6) and higher PaCO₂ on admission or within first hours after starting noninvasive positive pressure ventilation ^[40]

Comorbidities

• Children with the following comorbidities require more careful evaluation for pneumonia (in addition to consultation with appropriate subspecialist):

  • Congenital heart disease

  • Chronic lung disease of prematurity

  • Chronic respiratory conditions leading to infection, such as:

    • Cystic fibrosis

    • Bronchiectasis

  • Immune deficiency

• Threshold for admission of patients with these comorbidities is lower, and they should be monitored for possible worsening of disease

Monitoring

• Arrange clinical follow-up for outpatient-treated patients within 24 to 48 hours; consider hospitalization if condition has deteriorated

• Follow-up chest radiographs are not typically required for uncomplicated cases

• Monitoring of patients for discontinuation of COVID-19 isolation measures depends on disease severity and whether patient has significant immunocompromise ^[41]

  • Symptoms-based strategy is recommended for most immunocompetent children with mild or moderate disease severity

    • Isolate for 5 days and if symptoms are resolving (without fever for 24 hours), then follow by 5 days of wearing mask when around others

  • Test-based strategy may be necessary in consultation with infectious disease specialist for patients with severe to critical COVID-19 and patients with significant immunocompromise

    • Patients may require up to 20 days after onset of first symptom and negative results from nucleic acid amplification testing for SARS-CoV-2 RNA

Complications and Prognosis

Complications

• Necrotizing pneumonia

  • Rare complication; occurs most commonly in preschool-aged children ^[42]

  • Streptococcus pneumoniae is most common cause ^[42]

  • May also occur with other common bacterial pathogens

  • Patient develops parapneumonic effusion, pleural empyema, or bronchopleural fistula ^[42]

  • Predisposing conditions include congenital cysts, sequestrations, bronchiectasis, neurologic disorders, and immunodeficiency ^[43]

  • Consult infectious disease specialist and surgeon; may require chest tube/surgical intervention

• Empyema and pleural effusions

  • Uncommon in outpatients, but incidence increased in patients admitted to hospital ^[7]

  • Treatment options include therapeutic thoracentesis, drainage catheter placement, fibrinolytic therapy, pleurodesis, and surgery

• Bacteremia/sepsis

  • More likely to occur in patients with pneumonia complicated by moderate to large pleural effusion, empyema, or bronchopleural fistula

  • Blood cultures can guide need for antibiotic change

• Pneumatoceles

  • Occurs in approximately 2.4% of all infants and children with pneumonia ^[44]

  • Most commonly associated with Staphylococcus aureus and Streptococcus pneumoniae infections ^[45]

  • Thin-walled, air-filled intraparenchymal cysts develop secondary to localized bronchiolar and alveolar necrosis, allowing 1-way passage of air into interstitial space

  • With mechanical ventilation, patients have increased risk for developing complications related to pneumatoceles ^[44]

  • Most cases of pneumatoceles (more than 85%) resolve spontaneously, partially, or completely over weeks

• Recurrent pneumonia

  • Most patients have an underlying condition, such as: ^[46]

    • Oropharyngeal incoordination with aspiration syndrome (respiratory symptoms with feeding in those with gastroesophageal reflux)

    • Immune disorder (recurrent infections at other locations and failure to thrive)

    • Foreign body (consider if pneumonia in same anatomical location)

Prognosis

• Prognosis is good for children treated for community-acquired pneumonia on outpatient basis

• Morbidity and mortality are higher in hospitalized children

• Pediatric pneumonia is leading cause of mortality worldwide in children younger than 5 years ^[13]

Screening and Prevention

Prevention

• Interventions to prevent community-acquired pneumonia include breastfeeding, frequent handwashing, and avoidance of exposure to tobacco smoke

• Immunizations

  • Administer pneumococcal conjugate vaccine to prevent invasive pneumococcal disease in children aged 6 weeks to younger than 6 years ^[47][48]

  • Administer influenza, Haemophilus influenzae type b, pertussis, varicella, and measles vaccines according to recommended schedules ^[49]

  • Vaccination against COVID-19 is recommended for children aged 6 months and older ^[50]