Pneumonia in children: Inpatient treatment

INTRODUCTION — Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from hospital-acquired (nosocomial) pneumonia. CAP is a common and potentially serious illness with considerable morbidity.

The inpatient treatment of CAP and hospital-acquired pneumonia in children will be reviewed here. Our recommendations are largely consistent with practice guidelines provided by the Pediatric Infectious Diseases Society/Infectious Diseases Society of America and the British Thoracic Society [1,2]. (See 'Society guideline links' below.)

The outpatient treatment of CAP; the epidemiology, etiology, clinical features, and diagnosis of CAP in children; and the management of coronavirus disease 2019-related pneumonia are discussed separately:

●(See "Community-acquired pneumonia in children: Outpatient treatment".)

●(See "Pneumonia in children: Epidemiology, pathogenesis, and etiology".)

●(See "Community-acquired pneumonia in children: Clinical features and diagnosis".)

●(See "COVID-19: Management in children".)

HOSPITALIZATION

Indications — The decision to hospitalize a child with community-acquired pneumonia (CAP) is individualized based upon age, underlying medical problems, and clinical factors including severity of illness (table 1) [1-3]. Hospitalization generally is warranted for infants younger than three to six months of age, unless a viral etiology or Chlamydia trachomatis is suspected and they are not hypoxemic and relatively asymptomatic. Hospitalization is also warranted for a child of any age whose caregivers cannot provide appropriate care and assure compliance with the management plan. Additional indications for hospitalization include [1,2]:

●Hypoxemia (peripheral capillary oxygen saturation [SpO₂] <90 percent in room air at sea level)

●Dehydration, or inability to maintain hydration orally; inability to feed in an infant

●Moderate to severe respiratory distress: Respiratory rate >70 breaths/minute for infants <12 months of age and >50 breaths per minute for older children; retractions; nasal flaring; difficulty breathing; apnea; grunting

●Toxic appearance (more common in bacterial pneumonia and may suggest a more severe course) [4]

●Underlying conditions that may predispose to a more serious course of pneumonia (eg, cardiopulmonary disease, genetic syndromes, neurocognitive disorders), may be worsened by pneumonia (eg, metabolic disorder) or may adversely affect response to treatment (eg, immunocompromised host)

●Complications (eg, effusion/empyema, necrotizing process, abscess)

●Suspicion or confirmation that CAP is due to a pathogen with increased virulence, such as Staphylococcus aureus or group A Streptococcus (GAS)

●Failure of outpatient therapy (worsening or no response in 48 to 72 hours)

Indications for intensive care — The decision to treat a child with pneumonia in an intensive care setting is individualized, based upon clinical, laboratory, and radiologic findings. Treatment in an intensive care setting generally is warranted for children who manifest [1,2]:

●The need for ventilatory support beyond that which can be provided outside the intensive care unit (ICU; eg, mechanical ventilation, noninvasive positive pressure ventilation, failure to maintain SpO₂ >92 percent in fraction of inspired oxygen [FiO₂] >0.5)

●Signs of impending respiratory failure (lethargy, increasing work of breathing, and/or exhaustion with or without hypercarbia)

●Recurrent apnea or slow irregular respirations

●Cardiovascular compromise with progressive tachycardia and/or hypotension that requires or is refractory to fluid management

Care in the ICU also may be warranted for children with two or more of the following [1]:

●Respiratory rate >70 breaths/minute for infants <12 months of age and >50 breaths/minute for older children

●Apnea

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

●Partial pressure of oxygen in arterial blood (PaO₂):FiO₂ ratio <250

●Multilobar infiltrates

●Altered mental status

●Hypotension

●Pleural effusion

●Comorbid condition (eg, sickle cell disease, immune deficiency, immunosuppression)

●Unexplained metabolic acidosis

●Pediatric Early Warning Score >6 [5]

Infection control — CAP can be caused by a variety of microbial agents requiring a variety of infection-control measures [6]. If possible, rapid diagnostic tests should be performed at the time of admission to facilitate decisions regarding appropriate precautions. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Approach to microbiologic testing'.)

Hand washing is the single most important procedure to prevent the spread of infection. Guidelines for hand hygiene in health care settings can be accessed through the Centers for Disease Control and Prevention.

Additional infection control measures depend upon the likely pathogen(s), as follows [6,7]:

●Respiratory syncytial, parainfluenza, and human metapneumovirus – Gown and gloves (ie, contact precautions)

●Influenza and rhinoviruses, GAS (for the first 24 hours of treatment), methicillin-susceptible S. aureus, Bordetella pertussis (until patient has received five days of effective therapy), and Mycoplasma pneumoniae – Mask within 3 feet (ie, droplet precautions)

●Adenovirus – Contact and droplet precautions

●Methicillin-resistant S. aureus and other multidrug resistant organisms – Special organism precautions; contact and droplet precautions and dedicated patient equipment

Because isolation precautions are different for different pathogens, we favor simplifying the approach for viral respiratory pathogens by placing all patients with suspected viral respiratory tract infection on both contact and droplet precautions. These precautions are discussed separately. (See "Infection prevention: Precautions for preventing transmission of infection".)

SUPPORTIVE CARE — Supportive care includes ensuring adequate antipyresis, analgesia, respiratory support, and hydration.

Antipyresis and analgesia — Children hospitalized with pneumonia usually have fever and may have pleuritic chest pain, which can lead to shallow breathing and impaired ability to cough. Administration of antipyretics and/or analgesics (eg, acetaminophen, ibuprofen) can be used to keep the child comfortable; opioid analgesia is rarely necessary in children without a chest tube in place. Adequate pain control may promote coughing, which facilitates airway clearance. Antitussives should be avoided as none have been found to be effective in pneumonia [8]. Symptomatic treatment of cough is discussed separately. (See "The common cold in children: Management and prevention", section on 'Cough'.)

Respiratory support — Children hospitalized with pneumonia should receive ventilatory support as indicated by their clinical condition [1,2]. A supported sitting position may help to expand the lungs and improve respiratory symptoms [2].

We suggest that children with oxygen saturation [SpO₂] <95 percent in room air be treated with supplemental oxygen to maintain oxygen saturation ≥95 percent while they are in respiratory distress. Different thresholds for supplemental oxygen are suggested by other experts (eg, the British Thoracic Society guidelines suggest supplemental oxygenation to maintain oxygenation saturation >92 percent) [2]. Gentle bulb suction of the nares may be helpful in infants and children whose nares are blocked with secretions. Minimal handling seems to reduce oxygen requirements. (See "Continuous oxygen delivery systems for the acute care of infants, children, and adults".)

In children who are severely ill, it may be necessary to monitor carbon dioxide tension via blood gas analysis in addition to SpO₂ by oximetry. Hypercarbia is an important sign of impending respiratory failure, particularly in the young infant who is tiring but may have preserved oxygenation.

Fluid management — Children who cannot maintain adequate fluid intake because of breathlessness, fatigue, or risk of aspiration [9] may require intravenous (IV) fluid therapy. Nasogastric tubes should be avoided if possible because they may compromise breathing; if necessary, the smallest nasogastric tube possible should be used [2]. (See "Maintenance intravenous fluid therapy in children".)

Children with pneumonia are at risk for inappropriate secretion of antidiuretic hormone (SIADH) [10,11]. Serum electrolytes, fluid balance, and urine specific gravity should be monitored if there is clinical suspicion of SIADH [11]. Confirmation of SIADH is discussed separately. Isotonic, rather than hypotonic, IV fluids should be provided if SIADH is suspected. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)", section on 'Pulmonary disease' and "Maintenance intravenous fluid therapy in children".)

Chest physiotherapy — Chest physiotherapy is not beneficial for children with uncomplicated community-acquired pneumonia (CAP) [2]. In randomized and observational studies in children and adults, chest physiotherapy had no conclusive effect on length of hospital stay, duration of fever, or radiographic resolution [12-17].

Adjunctive glucocorticoid therapy — We do not routinely provide adjunctive glucocorticoid therapy to children hospitalized with pneumonia. Although a systematic review and meta-analysis of two small heterogeneous trials suggested that glucocorticoids reduce clinical failure (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) and time to clinical cure, additional studies in children are necessary before glucocorticoids can be routinely recommended [18-20]. A retrospective study evaluating adjunctive glucocorticoid therapy for children being treated for CAP in the outpatient setting found an association between adjunctive glucocorticoid therapy and treatment failure in children without underlying asthma [21].

Adjunctive glucocorticoids for adults with pneumonia are discussed separately. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Adjunctive glucocorticoids'.)

EMPIRIC THERAPY

Overview — Prompt initiation of antimicrobial therapy is crucial in children with community-acquired pneumonia (CAP). The initial treatment of children who are hospitalized with pneumonia is empiric (table 2A-B). Factors that must be considered include the spectrum of likely pathogens, antimicrobial susceptibility, simplicity, tolerability, palatability, safety, and cost [22].

The recommendations of most guidelines are based on in vitro susceptibilities of the most likely pathogen or pathogens, rather than evidence of the superiority of one antibiotic over another. Clinical response to empiric therapy and results of microbiologic studies, when available, help to determine whether additional evaluation or changes in therapy are necessary [1,2]. (See 'Specific therapy' below and 'Response to therapy' below and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Etiologic diagnosis'.)

There are few randomized controlled trials to guide the choice of empiric antibiotics in children with CAP. Decisions regarding empiric therapy are complicated by the substantial overlap in the clinical presentation of bacterial and nonbacterial pneumonias [23-25]. Treatment decisions usually are based upon algorithms that include patient age, epidemiologic and clinical information, and diagnostic laboratory and imaging studies (table 2A-B) [4]. The scope of empiric therapy (ie, narrow or broad) depends upon the severity of illness and presence of complications. Agents other than those suggested in the table may be more appropriate if there are clinical or epidemiologic features strongly suggestive of a specific cause (eg, mediastinal or hilar lymphadenopathy, residence in the central United States, and exposure to caves and/or bat guano suggestive of pulmonary histoplasmosis).

Consultation with a specialist in infectious disease may be helpful in children with medication allergies, comorbid conditions, failure of outpatient therapy, or multiple-drug-resistant organisms. Consultation with a pediatric pulmonologist may be helpful in children with recurrent pneumonia. (See "Community-acquired pneumonia in children: Clinical features and diagnosis" and "Community-acquired pneumonia in children: Outpatient treatment", section on 'Treatment failure'.)

Etiologic clues — Certain clinical and epidemiologic features can be used to determine the most likely pathogen(s) to aid in decisions regarding empiric therapy. Because these features often overlap, they cannot be used with complete confidence but are helpful in guiding empiric therapy until results of microbiologic tests are available (table 3). These features are discussed in greater detail separately. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clues to etiology' and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Etiologic clues'.)

Neonates — The treatment of neonatal pneumonia is discussed separately. (See "Neonatal pneumonia".)

Viral pneumonia — Most children younger than three to five years of age who are admitted to the hospital with pneumonia have viral pneumonia (eg, respiratory syncytial virus [RSV]) [26]. This is particularly true in the absence of lobar (or lobular) infiltrate and pleural effusion [4]. Viral pneumonia does not require antibiotic therapy unless a mixed infection or secondary bacterial infection is suspected. (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children", section on 'Clinical manifestations' and "Respiratory syncytial virus infection: Treatment in infants and children".)

No effective antivirals are available for most viral pneumonias, with a few important exceptions, described below.

COVID-19 pneumonia — The management of coronavirus 2019 (COVID-19)-related pneumonia is discussed separately. (See "COVID-19: Management in children", section on 'Management of hospitalized children'.)

Influenza pneumonia — Initiation of antiviral treatment for influenza (eg, oseltamivir) as soon as possible is recommended for children hospitalized with presumed influenza pneumonia; laboratory confirmation should not delay initiation of antiviral therapy. The diagnosis and treatment of influenza in children are discussed separately. (See "Seasonal influenza in children: Management", section on 'Antiviral therapy' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Diagnosis'.)

For children with influenza pneumonia in whom secondary bacterial pneumonia is suspected, empiric antibiotic therapy should include coverage for S. aureus, including methicillin-resistant S. aureus (MRSA). Coinfection with S. aureus may be particularly severe and rapidly fatal. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Empiric antimicrobial therapy'.)

Other viral pneumonias — Acyclovir can be used in the treatment of pneumonia due to herpes simplex virus or varicella zoster virus. Ganciclovir can be used in the treatment of pneumonia due to cytomegalovirus (CMV). (See "Treatment of varicella (chickenpox) infection", section on 'Individuals with complications'.)

Common respiratory viruses may cause serious infections in immunocompromised children and require consideration of antiviral therapy: ribavirin for RSV or parainfluenza and cidofovir for adenovirus. Concomitant immunotherapy is an additional consideration: palivizumab for RSV, CMV immune globulin for CMV, and intravenous immunoglobulin for the other viral etiologies. (See "Diagnosis, treatment, and prevention of adenovirus infection", section on 'Treatment' and "Respiratory syncytial virus infection: Treatment in infants and children".)

Uncomplicated bacterial pneumonia — Streptococcus pneumoniae is the most common bacterial cause of pneumonia in children of all ages [4,27]. Other potential bacterial pathogens that may need to be included in empiric therapy for hospitalized children include S. aureus, including MRSA, Streptococcus pyogenes (group A Streptococcus), Haemophilus influenzae type b (Hib; if unimmunized), other typeable non-b and nontypeable H. influenzae, and Moraxella catarrhalis [2,4,27-32].

The table provides several suggested parenteral empiric antibiotic regimens for uncomplicated bacterial pneumonia in hospitalized children when S. aureus is not a consideration (table 2A-B) [4,33,34]. The treatment of complicated CAP and severe CAP (particularly when S. aureus is a consideration) are discussed below. (See 'Complicated CAP' below and 'Severe CAP' below.)

Ampicillin or penicillin G generally provides adequate coverage for the fully immunized child (table 4) in communities without substantial prevalence of penicillin-resistant S. pneumoniae [1,35,36].

We suggest a third-generation cephalosporin (eg, cefotaxime, ceftriaxone) for children younger than 12 months and those who are not fully immunized because third-generation cephalosporins provide coverage for the beta-lactamase producing pathogens (eg, H. influenzae and M. catarrhalis) that may occur in these children. We also suggest third-generation cephalosporins for children with more severe illness (table 1) because third-generation cephalosporins provide coverage for a broader range of pathogens, including penicillin-resistant S. pneumoniae, than ampicillin [1,37,38].

When community-associated-MRSA (CA-MRSA) is considered a potential pathogen for CAP in children, we usually add clindamycin or vancomycin (depending upon local susceptibility patterns). The fifth-generation cephalosporin, ceftaroline, is an alternative. In the United States, ceftaroline is available for the treatment of pediatric CAP due to S. pneumoniae, methicillin-susceptible S. aureus, and H. influenzae in children ≥2 months of age [39]. Although ceftaroline has good in vitro activity against MRSA isolates [40] and has been effective in the treatment of pediatric CAP in randomized trials, few children included in the trials had documented MRSA [41,42].

A macrolide may be added (table 2A-B) if M. pneumoniae, Chlamydia pneumoniae, or legionellosis is suspected, although the benefits of combination therapy are uncertain. In a prospective population-based study of 1418 children hospitalized with radiographically confirmed CAP, the addition of a macrolide to beta-lactam antimicrobial therapy was not associated with decreased length of stay, intensive care admission, rehospitalization, or self-reported recovery [43]. In subgroup analysis, combination therapy was not associated with decreased length of stay in children in whom atypical bacteria were detected, children older than five years, children admitted to the intensive care unit (ICU), or children with wheezing. (See 'Atypical pneumonia' below.)

We suggest that children who require hospitalization for treatment of CAP be treated initially with parenteral antibiotics. However, oral amoxicillin may be an alternative for infants and children fully immunized against Hib and S. pneumoniae with uncomplicated pneumonia that is not thought to be due to S. aureus [44]. In a multicenter randomized trial, treatment with amoxicillin was equivalent to treatment with penicillin G in children with CAP who required hospital admission but did not have wheezing, hypotension, chronic pulmonary conditions (other than asthma), immunodeficiency, pleural effusion requiring drainage, or oxygen saturations <85 percent in room air [45]. The British Thoracic Society guidelines suggest that oral antibiotics are safe and effective even for children with severe pneumonia as long as they are able to tolerate oral fluids, are not vomiting, and do not have signs of septicemia or complicated pneumonia [2].

Atypical pneumonia — Atypical bacterial pathogens include C. trachomatis in afebrile infants, and M. pneumoniae and C. pneumoniae in older children and adolescents. The table provides several suggested empiric regimens for atypical bacterial pneumonia in hospitalized children (table 2A-B) [4,33].

For children older than four years with suspected atypical pneumonia, coverage for typical bacterial pathogens (eg, ampicillin or a third-generation cephalosporin) may be added to empiric coverage for atypical pathogens if there is strong evidence of a bacterial cause. Strong evidence of a bacterial cause includes white blood cell count >15,000/microL, C-reactive protein >35 to 60 mg/L (3.5 to 6 mg/dL), chills, or no response to outpatient therapy with a macrolide or doxycycline [4,46].

Fluoroquinolones (eg, levofloxacin, moxifloxacin) may be reasonable empiric therapy for the older child and adolescent with suspected atypical pneumonia who could possibly have pneumococcal pneumonia. The fluoroquinolones also may be used in the older child or adolescent who is unable to receive beta-lactam antibiotics (eg, history of immunoglobulin [Ig]E-mediated reaction or serious delayed reaction (table 5)). In addition to their excellent gram-negative spectrum, the fluoroquinolones are active against a number of the pathogens responsible for CAP, including beta-lactam-susceptible and nonsusceptible S. pneumoniae, M. pneumoniae (including macrolide-resistant M. pneumoniae), and C. pneumoniae [47]. However, S. pneumoniae resistant to levofloxacin have been identified [48].

Severe CAP

Severe CAP not requiring ICU admission — Children with severe CAP who do not require admission to the ICU (table 1) may benefit from combination empiric therapy with a macrolide and a beta-lactam antibiotic (eg, ampicillin or third-generation cephalosporin) (table 2A-B). Combination therapy improves coverage for resistant organisms and mixed bacterial/atypical bacterial infections.

If S. aureus is an etiologic consideration, options include:

●Adding either vancomycin or clindamycin (depending upon local susceptibility patterns) to the combination macrolide and beta-lactam, or

●Switching from the combination macrolide and beta-lactam to ceftaroline plus azithromycin

Antimicrobial therapy can be adjusted as necessary when results of microbiologic testing become available. Invasive diagnostic testing, including bronchoscopy with bronchoalveolar lavage, may be necessary for specific microbiologic diagnosis. (See 'Uncomplicated bacterial pneumonia' above and 'Atypical pneumonia' above and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Invasive studies'.)

Severe CAP requiring ICU admission — Children who are admitted to the ICU for serious or life-threatening infections require broad-spectrum empiric coverage that addresses potential beta-lactam resistance and CA-MRSA. (See 'Indications for intensive care' above.)

A suggested regimen for such children may include (table 2A-B) [49-51]:

●Vancomycin (table 6), and

●A third-generation cephalosporin (cefotaxime 150 mg/kg per day IV in four divided doses up to a maximum of 8 g/day or ceftriaxone 100 mg/kg per day IV in two divided doses up to a maximum dose of 4 g/day), and

●Azithromycin 10 mg/kg once per day IV for two days (maximum 500 mg/day), followed by 5 mg/kg once per day IV (maximum 250 mg/day), and possibly

●Nafcillin or oxacillin 150 to 200 mg/kg per day IV in four divided doses; maximum 12 g/day if S. aureus is likely (methicillin-susceptible S. aureus is more rapidly killed by nafcillin than by vancomycin), and possibly

●Antiviral therapy for influenza, if the child is hospitalized during influenza season; laboratory confirmation of influenza should not delay initiation of antiviral therapy (see "Seasonal influenza in children: Management", section on 'Antiviral therapy')

This combination is necessary because of reports of treatment failure resulting from treatment of nonsusceptible S. pneumoniae with beta-lactams, clindamycin resistance among S. pneumoniae (which, however, is becoming less prevalent), and concern for MRSA [49]. Virtually all strains of MRSA are susceptible to vancomycin [50]. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'MRSA infections'.)

When treating with vancomycin, renal function and serum trough levels or dosing to achieve an area under the curve/minimum inhibitory concentration (AUC:MIC) ratio >400 should be monitored in an attempt to assure therapeutic efficacy and limit toxicity. In adults, vancomycin trough levels between 15 and 20 microgram/mL have been suggested to improve clinical outcomes for complicated infections due to S. aureus [51-53]. Similar trough levels may not be needed in children to achieve an AUC:MIC >400, and further studies are needed to evaluate the clinical effectiveness and safety of these dosing recommendations in children [53-58].

For children in whom S. aureus is likely, linezolid could be substituted for vancomycin and nafcillin in the above regimen. Linezolid is an oxazolidinone antibiotic with activity against gram-positive cocci, including beta-lactam-resistant S. pneumoniae and MRSA. However, against S. aureus it is only bacteriostatic. Linezolid is dosed according to age as follows:

●Age <12 years – 10 mg/kg per dose IV every 8 hours (maximum 600 mg/dose)

●Age ≥12 years – 600 mg every 12 hours

An alternative non-vancomycin-containing regimen for children in whom S. aureus is a consideration consists of:

●Ceftaroline

•Age ≥2 months and <2 years – 8 mg/kg per dose IV every 8 hours

•Age ≥2 years and <18 years:

-Weight ≤33 kg – 12 mg/kg per dose IV every 8 hours

-Weight >33 kg – 400 mg/dose IV every 8 hours or 600 mg/dose IV every 12 hours

•Age ≥18 years – 600 mg/dose IV every 12 hours

●Plus azithromycin 10 mg/kg once per day IV for two days (maximum 500 mg/day), followed by 5 mg/kg once per day IV (maximum 250 mg/day), and possibly

●Antiviral therapy for influenza, if the child is hospitalized during influenza season; laboratory confirmation of influenza should not delay initiation of antiviral therapy (see "Seasonal influenza in children: Management", section on 'Antiviral therapy')

Complicated CAP — Complicated CAP (eg, parapneumonic effusion, necrotizing process, lung abscess) requires a broader spectrum of antibiotic coverage if etiologies other than S. pneumoniae are being considered. The expanded spectrum should include coverage for beta-lactam-resistant isolates including CA-MRSA. Coverage for anaerobes and gram-negative organisms also may be necessary for children with lung abscess [59]. Antimicrobial therapy can be adjusted as necessary when results of microbiologic testing become available. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Complications' and "Management and prognosis of parapneumonic effusion and empyema in children".)

Complicated CAP requires a prolonged course of antimicrobial therapy, usually initiated parenterally [60]. Appropriate regimens may include [33]:

●Either ceftriaxone 100 mg/kg IV in two divided doses (maximum 4 g/day) or cefotaxime 150 mg/kg per day IV in four divided doses (maximum 8 g/day)

If S. aureus or anaerobes are a consideration, add clindamycin 30 to 40 mg/kg per day IV in three or four divided doses (maximum 2.7 g/day).

Vancomycin (table 6) is an alternative to clindamycin if the patient is allergic to clindamycin or if clindamycin-resistant S. aureus is prevalent in the community. The threshold prevalence of clindamycin-resistant MRSA (constitutive plus inducible) for choosing vancomycin varies from center to center, usually ranging from 10 to 25 percent, in an effort to balance the benefit of definitive therapy for the patient with the risk of increasing vancomycin resistance in the community. Additional considerations in the decision to choose vancomycin include the prevalence of MRSA in the community, severity of illness, renal function and/or use of other nephrotoxic agents, and turnaround time for susceptibilities. When treating with vancomycin, renal function and serum trough levels or dosing to achieve an AUC:MIC ratio of >400 should be monitored in an attempt to assure therapeutic efficacy and limit toxicity. In adults, vancomycin trough levels between 15 and 20 microgram/mL have been suggested to improve clinical outcomes for complicated infections due to S. aureus [51-53]. Similar trough levels may not be needed in children to achieve an AUC:MIC >400, and further studies are needed to evaluate the clinical effectiveness and safety of these dosing recommendations in children [53-58]. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'MRSA infections'.)

●Monotherapy with ceftaroline is an alternative if S. aureus is a consideration:

•Age ≥2 months and <2 years – 8 mg/kg per dose IV every 8 hours

•Age ≥2 years and <18 years:

-Weight ≤33 kg – 12 mg/kg per dose IV every 8 hours

-Weight >33 kg – 400 mg/dose IV every 8 hours or 600 mg/dose IV every 12 hours

•Age ≥18 years – 600 mg/dose IV every 12 hours

In a multicenter randomized trial in 40 children with complicated community-acquired bacterial pneumonia (only one had documented MRSA), clinical cure rates at the end of treatment were similar with ceftaroline monotherapy and combination ceftriaxone and vancomycin (approximately 80 percent) [42].

●For children with lung abscess that is thought to be secondary to aspiration, ampicillin-sulbactam 150 to 200 mg/kg per day of the ampicillin component IV in four divided doses (maximum 8 g/day for the ampicillin component) alone may be effective. (See 'Aspiration pneumonia' below.)

The duration of therapy and other considerations in the management of complicated pneumonia depend upon the type of complication:

●Parapneumonic effusion/empyema – The treatment of parapneumonic effusion and empyema is discussed in detail separately. (See "Management and prognosis of parapneumonic effusion and empyema in children".)

●Necrotizing pneumonia – Treatment of necrotizing pneumonia requires a prolonged course of antibiotic therapy. The duration is determined by the clinical response but is usually a total of four weeks or two weeks after the patient is afebrile and has improved clinically. Interventional procedures (eg, percutaneous drainage catheter placement) should be performed cautiously in children with necrotizing pneumonia; such procedures increase the risk of complications, such as the development of bronchopleural fistulae [59,61-63].

●Lung abscess – Treatment of lung abscess requires a prolonged course of antibiotic therapy. The duration is determined by the clinical response and radiographic resolution of the abscess or stabilization of a small lesion. The usual course is a total of three to four weeks or two weeks after the patient is afebrile and has clinical improvement [60]. The average duration of fever is four to eight days. Antibiotic therapy can be changed from the parenteral to the oral route when the child is improving clinically and is afebrile. Eighty to 90 percent of lung abscesses in children resolve with antibiotic therapy alone and spontaneous drainage through the tracheobronchial tree, provided that any bronchial obstruction is removed [64].

In cases that fail to resolve with antibiotics alone, needle aspiration or percutaneous catheter drainage may provide diagnostic information and therapeutic benefit without the increased risk of complications that occurs in children with necrotizing pneumonia [59,61,65,66]. Percutaneous drainage may be warranted in children with lung abscess whose condition fails to improve or worsens after 72 hours of antibiotic therapy [67]. At least three weeks of IV antibiotic therapy should be delivered before lobectomy is considered for treatment failure [68].

●Pneumatocele – Most pneumatoceles involute spontaneously [69-71]. However, on occasion, pneumatoceles may result in pneumothorax [72].

Hospital-acquired pneumonia — Empiric treatment of hospital-acquired pneumonia should include coverage for S. aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes. Acceptable broad spectrum regimens usually include an aminoglycoside (for gram-negative pathogens) and another agent to address gram-positive pathogens and anaerobes:

●Aminoglycoside (usually gentamicin; amikacin if extended-spectrum or Amp C beta-lactamase-producing gram-negative rods are possible etiologies) plus one of the following:

•Piperacillin-tazobactam 300 mg/kg per day IV in four divided doses up to a maximum of 12 g/day, or

•Meropenem 60 mg/kg per day IV in three divided doses, up to a maximum of 6 g/day if extended-spectrum or Amp C beta-lactamase-producing gram-negative rods are possible etiologies, or

•Ceftazidime 125 to 150 mg/kg per day in three divided doses; maximum of 6 g/day, or

•Cefepime 150 mg/kg per day in three divided doses; maximum of 4 g/day, or

•Clindamycin 30 to 40 mg/kg per day in three or four divided doses; maximum 2.7 g/day (for patients unable to receive beta-lactam antibiotics [eg, history of IgE-mediated reaction or severe delayed hypersensitivity reaction (table 5)])

The combination of amikacin and meropenem should be used if extended-spectrum beta-lactamase-producing gram-negative rods are a consideration. The combination of amikacin and either meropenem or cefepime should be used if AmpC beta-lactamase-producing gram-negative rods are a consideration.

The cephalosporin/aminoglycoside combination lacks anaerobic coverage, so it should not be used when aspiration pneumonia is a possibility. (See 'Aspiration pneumonia' below.)

Vancomycin should be added to the empiric regimen if MRSA is a consideration. An agent other than piperacillin-tazobactam should be chosen as the second agent, if feasible, when vancomycin is added because the combination of these two drugs has been associated with increased risk of acute kidney injury [73,74]. Ceftaroline is an alternative to vancomycin if MRSA is a consideration.

Aspiration pneumonia — Empiric antibiotic regimens for community-acquired aspiration pneumonia must cover oral anaerobes. Appropriate antibiotic regimens for hospitalized children include [67]:

●Ampicillin-sulbactam 150 to 200 mg/kg per day of the ampicillin component IV in four divided doses; maximum 8 g/day of the ampicillin component, or

●Clindamycin 30 to 40 mg/kg per day IV in three or four divided doses to a maximum of 2.7 g/day if MRSA etiology is suspected or for patients unable to receive beta-lactam antibiotics (eg, history of IgE-mediated reaction or severe delayed hypersensitivity reaction (table 5)).

In neurologically compromised older adolescents prone to aspiration events, empiric treatment for CAP with a fluoroquinolone like moxifloxacin (400 mg once daily) may be reasonable. Moxifloxacin has activity against anaerobic bacteria, as well as the usual treatable causes of CAP (S. pneumoniae, M. pneumoniae, and C. pneumoniae).

Appropriate antibiotic regimens for children with health care-associated aspiration who are known to be colonized with unusual gram-negative pathogens (eg, Klebsiella pneumoniae) include:

●Piperacillin-tazobactam 300 mg/kg per day IV in four divided doses up to a maximum of 12 g/day, or

●Meropenem 60 mg/kg per day IV in three divided doses, up to a maximum of 6 g/day

Vancomycin should be added to the empiric regimen if MRSA is a consideration. Meropenem may be preferred for gram-negative coverage if vancomycin is added because the combination of vancomycin and piperacillin-tazobactam has been associated with increased risk of acute kidney injury [73,74]. However, this risk must be weighed against the development of meropenem resistance, particularly in closed units. Ceftaroline is an alternative to vancomycin if MRSA is a consideration.

Patients with contraindications to beta-lactam antibiotics (eg, history of IgE-mediated reaction or severe delayed hypersensitivity reaction (table 5)) can be treated with a combination of clindamycin and an aminoglycoside.

Immunocompromised host — Empiric treatment for pneumonia in immunocompromised hosts also requires broad-spectrum gram-positive and gram-negative coverage, similar to that required for hospital-acquired pneumonia, with the addition of vancomycin if MRSA is considered, and possibly trimethoprim-sulfamethoxazole for Pneumocystis jirovecii (formerly P. carinii). Empiric regimens may need to be modified once results of cultures and antibiotic susceptibility testing are available. Invasive testing may be required to obtain a satisfactory specimen in such patients (see "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Invasive studies'). Treatment of CAP in the immunocompromised host should occur in consultation with an infectious disease specialist.

An aggressive approach to specific microbial diagnosis is indicated in immunocompromised hosts with clinically significant pneumonias. For patients with an endotracheal tube in place, specific microbial diagnosis may involve early flexible bronchoscopy for bronchoalveolar lavage with viral, fungal, and bacterial diagnostic studies. Although the protected specimen brush technique has been utilized in some settings, quantitative bacterial cultures are more commonly used to differentiate colonization from true lower respiratory tract infection. (See "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Diagnostic indications' and "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic evaluation'.)

SPECIFIC THERAPY — Once results of microbiologic tests are available, antimicrobial therapy can be directed toward the responsible pathogen or pathogens. Specific antimicrobial and/or supportive therapy for the pathogens that commonly cause community-acquired pneumonia (CAP) in children is discussed in the topic reviews listed below.

●S. pneumoniae (see "Pneumococcal pneumonia in children", section on 'Specific therapy')

●Group A Streptococcus – Penicillin G or ampicillin are the preferred parenteral agents for pneumonia caused by group A Streptococcus; the doses are as follows [1]:

•Penicillin G 100,000 to 250,000 units/kg per day intravenously (IV) divided in four or six doses

•Ampicillin 200 mg/kg per day IV divided in four doses

Alternative parenteral agents include cefazolin, ceftriaxone or cefotaxime, clindamycin (if susceptible), and vancomycin (for children unable to receive beta-lactam antibiotics [eg, history of IgE-mediated reaction or severe delayed hypersensitivity reaction (table 5)]) [1].

Amoxicillin or penicillin V are the preferred oral agents; the doses are as follows [1]:

•Amoxicillin 50 to 75 mg/kg per day orally divided in two doses (maximum 4 g/day)

•Penicillin V 50 to 75 mg/kg per day orally divided in three doses (maximum 2 g/day)

Alternative oral agents include cephalexin 75 to 100 mg/kg per day in three or four divided doses (maximum 4 g/day) or clindamycin (if susceptible) 40 mg/kg per day orally divided in three doses (maximum 1.8 g/day) [1].

●Haemophilus influenzae (typeable or nontypeable) (see "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Directed treatment')

●M. pneumoniae (see "Mycoplasma pneumoniae infection in children", section on 'Management')

●C. pneumoniae (see "Pneumonia caused by Chlamydia pneumoniae in children")

●Methicillin-susceptible S. aureus (MSSA) – MSSA pneumonia may be treated with oxacillin, nafcillin, or cefazolin [1,4]

●Methicillin-resistant S. aureus (MRSA) (see "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Definitive antimicrobial therapy')

●Respiratory syncytial virus (see "Respiratory syncytial virus infection: Treatment in infants and children")

●Influenza (see "Seasonal influenza in children: Management", section on 'Antiviral therapy')

●Parainfluenza (see "Parainfluenza viruses in children", section on 'Treatment')

●Adenovirus (see "Diagnosis, treatment, and prevention of adenovirus infection", section on 'Treatment')

●Human metapneumovirus (see "Human metapneumovirus infections", section on 'Treatment')

DURATION OF TREATMENT

Parenteral therapy — There are few data to guide decisions about the duration of parenteral therapy for community-acquired pneumonia (CAP) [2,75]. It is common to switch to oral therapy in patients who have received parenteral antibiotics when the patient has become afebrile for 24 to 48 hours and is not having emesis [76].

Total duration — There are few randomized controlled trials to guide decisions about the appropriate duration of antimicrobial therapy for radiographically confirmed childhood pneumonia [2]. Clinical practice assigns duration of therapy according to the host, causative agent, and severity.

●Uncomplicated cases – For children hospitalized with uncomplicated pneumonia, we generally treat with a seven-day course of combined parenteral and oral therapy, although a course of five to seven days may also be effective.

Although evidence from randomized trials in children is lacking, there is some evidence to support five to seven days of therapy. In a single-center observational study in children ≥6 months of age who were hospitalized with uncomplicated community-acquired pneumonia (CAP), rates of treatment failure were similar among those who received antibiotic therapy for 5 to 7 days and 8 to 14 days (3 versus 6 percent, odds ratio 0.48, 95% CI 0.18-1.20) [77]. Treatment failure was defined as a composite of unanticipated emergency department or outpatient visits, readmission, or death within 30 days after completion of antibiotics. Randomized trials in adult patients with mild to moderate CAP also suggest that outcomes in patients treated for less than seven days are similar to those in patients treated longer. These trials are discussed separately. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Duration of therapy'.)

●Complicated cases – Treatment of complications, such as necrotizing pneumonia and lung abscess, requires a prolonged course of antibiotic therapy, usually initiated parenterally. The duration is determined by the clinical response but usually is either a total of three to four weeks or a total of two weeks after the patient is afebrile and has improved clinically. Some infectious diseases specialists use an erythrocyte sedimentation rate value of <20 mm/hour as a laboratory indicator that the duration of therapy has been sufficient. (See 'Complicated CAP' above.)

RESPONSE TO THERAPY — The following clinical parameters can be monitored to assess response to treatment [1,2]:

●Temperature

●Respiratory rate

●Heart rate

●Peripheral capillary oxygen saturation (SpO₂)

●Work of breathing (eg, retractions, nasal flaring, grunting)

●Chest examination (extent of abnormal or absent breath sounds; extent of dullness to percussion)

●Mental status

●Ability to maintain oral intake and hydration

The frequency of monitoring depends upon the severity of illness. In patients who are receiving oxygen supplementation, oxygen saturation should be evaluated regularly. Evaluation for hypercarbia may be necessary in children with severe respiratory distress, as oxygenation may be preserved.

The respiratory status of children with community-acquired pneumonia (CAP) who are appropriately treated should improve within 48 to 72 hours [1]. However, fevers may persist for several days after initiation of appropriate therapy [67].

Treatment failure — In children who fail to improve as anticipated, the following possibilities must be considered [1,2,78,79]:

●Alternative or coincident diagnoses (eg, foreign body aspiration) (see "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Differential diagnosis')

●Ineffective antibiotic coverage (lack of coverage for the actual etiology or resistant organism)

●Development of complications (see "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Complications')

●Underlying immunodeficiency condition

The history should be reviewed with special attention to the possibility of foreign body aspiration and geographic or environmental exposures associated with pathogens not treated by the empiric regimen (table 7).

Changes in laboratory parameters (eg, peripheral white blood cell count, inflammatory markers [if obtained initially]) may provide information about disease progression. Repeat radiographs or additional imaging studies can help to assess the degree of parenchymal involvement and evaluate for complications or anatomic abnormalities [1]. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Complications' and "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)

Depending upon the severity of illness, more aggressive attempts may need to be made to establish a microbiologic diagnosis (eg, induced sputum [80], bronchoscopy with bronchoalveolar lavage, percutaneous needle aspiration, or lung biopsy). In children with lung abscess whose condition fails to improve or worsens after 72 hours of antibiotic therapy, needle aspiration or percutaneous catheter drainage may provide diagnostic information and therapeutic benefit [61,65-67]. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Invasive studies'.)

DISCHARGE CRITERIA — Discharge criteria for children who have been admitted to the hospital with community-acquired pneumonia (CAP) have not been standardized, but typically include [1,67]:

●Improvement of vital signs

●Ability to maintain adequate fluid and nutrition orally

●Ability to maintain oxygen saturation ≥90 percent in room air

●Improvement in respiratory status

●Overall clinical improvement including level of activity, appetite, and decreased fever for at least 12 to 24 hours

●Stable and/or baseline mental status

●Caregivers' ability to administer and child's ability to comply with home antibiotic regimen

●Safe and compliant home environment

Outpatient parenteral antibiotic therapy — Outpatient parenteral antimicrobial therapy (OPAT) is an option for selected patients who require prolonged treatment (usually for complicated CAP that for some reason cannot be treated with an oral antibiotic) and have stabilized clinically [67,81,82]. Eligibility for OPAT requires a suitable home environment and a pharmacologic agent with a reasonable dosing schedule [83]. Decisions regarding OPAT should involve the caregivers, an infectious disease specialist (or clinician knowledgeable about the use of antimicrobial agents in OPAT), a hospital pharmacist, and the primary care provider. The services of a visiting nurse may be required for home visits, education and observation of caregiver administration, and/or obtaining blood samples for therapeutic monitoring.

FOLLOW-UP

Clinical course — Children with pneumonia should be seen by their primary care provider soon after discharge to ensure that clinical improvement continues and antibiotic therapy is being taken as prescribed [67]. Decisions regarding the timing of clinical follow-up should involve the child's primary care provider and the clinical status of the child at the time of discharge.

Children who are appropriately treated for pneumonia should gradually improve with time. Cough may persist for as long as three to four months after viral pneumonia or pertussis. Children who are recovering from typical or atypical bacterial pneumonia may continue to cough for several weeks and have moderate dyspnea on exertion for two to three months [84]. Symptomatic treatment of cough is discussed separately. (See "The common cold in children: Management and prevention", section on 'Cough'.)

Radiographs — Follow-up radiographs are not necessary in asymptomatic children with uncomplicated community-acquired pneumonia (CAP), including round pneumonia [85]. However, in children with complicated CAP or CAP that required intervention, follow-up radiographs help to ensure resolution [2,86]. Follow-up radiographs also may be helpful in children with recurrent pneumonia, persistent symptoms, severe atelectasis, or unusually located infiltrates [2,67,87]. When follow-up radiographs are indicated, they should be obtained two to three weeks after hospital discharge [67,88]. Other conditions that should be considered if symptoms persist in children with round pneumonia include congenital lung sequestration, pulmonary arteriovenous malformation, metastatic Wilms tumor, cavitary necrosis, pleural pseudocyst, and primary lung carcinoma [85,87,89-92].

Several studies have evaluated the utility of follow-up radiographs in cohorts of children with acute radiologically proven CAP [93-98]. Three of the studies included clinical as well as radiologic follow-up at three to seven weeks after initial diagnosis [93-96]. In each of these studies, follow-up radiographs were normal or improved in asymptomatic children. Residual radiographic findings, even when present, did not result in additional therapy.

PROGNOSIS — Most otherwise healthy children with pneumonia recover without sequelae, even if the pneumonia is complicated [62,63,67,99]. In a multicenter cohort study, approximately 3 percent of 82,566 children hospitalized with pneumonia were readmitted with pneumonia within 30 days of discharge; 8 percent were readmitted for any reason. Readmission was more common among children younger than one year and children with chronic medical conditions [100].

Although some data suggest that nearly one-half of children who are hospitalized for viral pneumonia have symptoms of asthma five years after hospitalization, it is not clear whether this is related to unrecognized asthma at the time of presentation with pneumonia or a tendency to develop asthma after community-acquired viral pneumonia [101,102].

The overall pneumonia mortality rate in developed countries is <1 per 1000 per year [26,103]. Pneumococcal pneumonia case fatality rates (not adjusted for comorbid conditions) for children in the United States were estimated to be 4 percent in children younger than two years and 2 percent in children 2 to 17 years before the introduction of pneumococcal conjugate vaccines [104].

The introduction of pneumococcal conjugate vaccines has resulted in a dramatic reduction (37 to 80 percent) in invasive disease and mortality rates in the countries in which they have been introduced [105]. However, pneumococcal pneumonia mortality rates have not been specifically examined. Data from the United States Pediatric Multicenter Pneumococcal Surveillance Study Group demonstrated overall pneumococcal mortality rates of 1 percent after the introduction of PCV7 (during 2006 to 2009) and 0 percent after the introduction of PCV13 (during 2011 to 2014) [106]. In a study from eastern Gambia, introduction of a nine-valent pneumococcal conjugate vaccine resulted in reduced all-cause mortality (25.2 versus 30.1 per 1000 child-years, a 16 percent reduction) [107]. (See "Pneumococcal vaccination in children", section on 'Efficacy and effectiveness'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric pneumonia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Pneumonia in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Hospitalization and supportive care – The decision to hospitalize a child with community-acquired pneumonia (CAP) must be individualized and is based upon age, underlying medical problems, and severity of illness (table 1). (See 'Indications' above.)

CAP can be caused by a variety of microbial agents, requiring a variety of infection-control measures. (See 'Infection control' above.)

Supportive care for children hospitalized with pneumonia includes provision of adequate respiratory support, hydration, antipyresis, and analgesia. (See 'Supportive care' above.)

●Empiric antimicrobial therapy – Children with CAP who are hospitalized are treated empirically until information from the microbiologic evaluation is available to direct therapy toward a specific pathogen. Decisions regarding empiric antimicrobial therapy for CAP in children are usually based upon age, unless there are other overriding epidemiologic or clinical factors to suggest a specific etiologic agent (table 2A-B). (See 'Overview' above and "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)

•We recommend that empiric antibiotic therapy for presumed bacterial pneumonia in hospitalized children include coverage for Streptococcus pneumoniae (table 2A-B) (Grade 1B). (See 'Uncomplicated bacterial pneumonia' above.)

•Extended empiric coverage may be indicated for children with complicated or severe pneumonia, particularly those who require admission to an intensive care unit (ICU) (table 2A-B). (See 'Complicated CAP' above and 'Severe CAP requiring ICU admission' above.)

●Specific antimicrobial therapy – When results of microbiologic tests are available, antibiotic therapy can be directed toward the specific pathogen recovered. (See 'Specific therapy' above.)

●Switch to oral therapy – Oral therapy typically is initiated when the patient has been afebrile for 24 to 48 hours and can tolerate oral intake. The total duration of antibiotic therapy is usually seven days for uncomplicated CAP, although a course of five to seven days may also be effective. Up to four weeks of antimicrobial therapy may be necessary for complicated CAP. (See 'Duration of treatment' above.)

●Treatment failure – The respiratory status of children receiving appropriate therapy for CAP should improve within 48 to 72 hours. Children who fail to improve as anticipated may be receiving inadequate antibiotic therapy, have developed complications, or have an alternative or coincident diagnosis. (See 'Treatment failure' above.)

●Clinical course and follow-up – Children recovering from CAP may continue to have cough for several weeks to four months, depending upon the etiology. Those recovering from typical or atypical bacterial pneumonia may have moderate dyspnea on exertion for two to three months. (See 'Clinical course' above.)

Follow-up radiographs are not necessary in asymptomatic children with uncomplicated CAP. However, in children with complicated CAP or CAP that required intervention, follow-up radiographs help to ensure resolution. Follow-up radiographs two to three weeks after completion of therapy may be helpful in children with recurrent pneumonia, persistent symptoms, severe atelectasis, or unusually located infiltrates. (See 'Radiographs' above.)

Most otherwise healthy children who develop pneumonia recover without any long-term sequelae. (See 'Prognosis' above.)