Background

Acute infections of the respiratory tract are among the most common infections in children and one of the most common reasons for a visit to the emergency department. Although most of these infections involve the upper respiratory tract, physicians caring for children in the emergency department frequently encounter lower respiratory infections, most notably bronchiolitis and pneumonia. Bronchiolitis is primarily seen in children younger than 2 years and is defined as wheezing and congestion due to a viral or bacterial lung infection. Pneumonia is an inflammation of the lung tissue and is most often due to an infection but occasionally may follow a noninfectious insult. Although the diagnosis of pneumonia may be suggested by clinical signs and symptoms, pneumonia is diagnosed by an abnormal chest radiograph showing pulmonary infiltrates. The clinical picture of pneumonia is highly variable and may range from a mild illness to life-threatening disease. Given the wide variety of agents that can cause pneumonia and the limitations of diagnostic testing, determination of a precise etiologic diagnosis may be difficult. Clinical, laboratory, and radiographic findings sometimes suggest a specific organism, but the definitive etiology often remains unknown.

Epidemiology

Infection rates for pneumonia in children vary inversely with age, averaging 40 per 1000 in preschool-age children and decreasing gradually to 7 per 1000 in 12- to 15-year-olds, with a male predominance of 2 : 1. Three fourths of all deaths from pneumonia result from bacterial infections.

The causative organisms also vary with the age of the child. Because the organism is not definitively identified in most pneumonia cases, it is difficult to determine the true incidence of the specific etiologic agents.¹ Overall, it has been estimated that viral agents cause 60 to 90% of pneumonias.² Viral agents are more common in younger children. Bacteria predominate in neonates but are a less frequent causative agent in toddlers and older children. Outside of the neonatal period, the incidence of bacterial agents is stable throughout different age groups.² Mixed viral and bacterial infections or concomitant bacterial infections may occur in one third of pneumonias.^2,3 Chlamydia trachomatis is a unique cause of pneumonia in infants 3 to 19 weeks old. Bordetella pertussis classically occurs in children younger than 1 year but also occurs in older children and adolescents.^4,5 Mycoplasma pneumoniae is one of the most common causes of pneumonia among children older than 5 years and may play a role in younger children.^6,7 Chlamydia pneumoniae is more often seen in children older than 5 years but also may cause infection in younger children.^7,8

Among bacteria, group B streptococci and gram-negative bacilli predominate in neonates. Ureaplasma urealyticum and Listeria monocytogenes may cause illness in infants younger than 3 months.¹ Streptococcus pneumoniae is the leading bacterial cause of pneumonia in all age groups beyond the newborn period; Haemophilus influenzae and Staphylococcus aureus are less common etiologic agents, most often seen in the first years of life. The incidence of H. influenzae type b disease has decreased by 90% since the onset of immunization of infants and young children.⁹ The heptavalent pneumococcal conjugate vaccine Prevnar (Lederle Laboratories/Wyeth-Ayerst Pharmaceuticals, Wayne, N.J.) was licensed by the U.S. Food and Drug Administration in 2000 and is recommended as a primary series at 2, 4, and 6 months of age, with a fourth booster dose given at 12 to 15 months of age. Clinical trials suggested 85% protection against serotype-specific cases of bacteremic pneumonia.¹⁰ Studies have also shown a decrease in carriage rates of the serotypes included in the daycare setting.¹¹ Pneumococcal polysaccharide vaccines have been recommended for children older than 2 years at high risk for pneumococcal disease since 1985, but they are not immunogenic in younger patients. Pneumococcal vaccine has also been shown to provide some protection against viral pneumonia. One study found a 31% reduction in the incidence of pneumonia associated with seven respiratory viruses in hospitalized children. This may be because viral pneumonia in hospitalized children is often associated with concurrent pneumococcal infection.¹² Other, less common bacterial agents include group A streptococci, Neisseria meningitidis, and anaerobic bacteria, the last being particularly common in the setting of aspiration pneumonia. Unusual causes of pneumonia include Pseudomonas aeruginosa, Legionella pneumophila, Pneumocystis jiroveci, and rickettsial infections. The incidence of Mycobacterium tuberculosis is increasing in the United States, particularly in urban and low-income areas and among nonwhite racial or ethnic groups. Infants and adolescents are at highest risk in the United States.

Respiratory syncytial virus (RSV) and parainfluenza are the most frequent viral agents in infants younger than 1 year. Viruses that may be responsible for neonatal pneumonia include rubella, cytomegalovirus (CMV), and herpes simplex virus. Other viral agents include influenza, adenovirus, rhinovirus, enterovirus, measles, varicella, and Epstein-Barr virus. The immunocompromised host is susceptible to all these causes of pneumonia and mixed and opportunistic infections, including bacterial, viral (CMV, varicella), protozoan (P. jiroveci), and fungal disease.

Pathophysiology

The lung is protected from infection by a variety of local and systemic immune mechanisms. Passively acquired maternal antibodies are important in protection against S. pneumoniae and H. influenzae infections during the first few months of life. Children with altered protective mechanisms are at increased risk for development of pneumonia; this includes children with congenital anatomic abnormalities (cleft palate, tracheoesophageal fistulas, pulmonary sequestration, congenital cystic adenomatoid malformation), immune deficiencies, neurologic alterations that predispose to aspiration (coma, seizures, cerebral palsy, general anesthesia), and alterations in quality of secreted mucus (cystic fibrosis [CF]).

Bacterial pneumonia and mycoplasmal infections are transmitted most often person to person by droplet aspiration. Asymptomatic upper airway colonization often occurs in children and may spread infection to other children.¹³ Less commonly, bacterial pneumonia also may result from hematogenous spread from a distant focus or during primary bacteremia. Viral agents that cause pneumonia proliferate in the upper respiratory tract and spread contiguously to involve the lower respiratory tract. Viruses such as varicella, CMV, herpes simplex, Epstein-Barr, measles, and rubella also may infect the lung through hematogenous spread.

Symptoms and Signs

Bacterial Pneumonia

Viral Pneumonia

Viral pneumonia occurs more commonly in the winter and generally has a gradual onset during several days, often with associated cough, congestion, and low-grade fever. Tachypnea may be the only physical finding; however, retractions, rales, and wheezing are common, with grunting, cyanosis, lethargy, dehydration, and apnea apparent in more severely affected children. The diagnosis of viral pneumonia is often made clinically. A chest radiograph is usually not needed for diagnosis of a child with viral pneumonia who presents during the winter months with fever, cough, congestion, and wheezing. Rapid antigen testing is often used in the diagnosis of RSV infection or influenza A and B, but it is not highly sensitive. However, for cohorting of similar patients in the hospital or when the use of antivirals is being considered, definitive diagnosis may be helpful. Other viral agents may be diagnosed with culture of nasopharyngeal secretions. Although in the past the use of viral cultures was limited by the time required to grow viruses, improved culture techniques may yield results within 2 days and prove useful if a cause needs to be established.

The WBC count is variable but tends to be less than 15,000/mm³ with lymphocyte predominance. Radiographic findings typically include hyperinflation and peribronchial thickening with diffuse increase in interstitial findings. Patchy areas of consolidation may be present, representing lobular atelectasis or alveolar pneumonia. Although lobar consolidation and small pleural effusions may occur in viral pneumonia, these findings are more consistent with a bacterial cause.

Most viral pneumonias resolve without specific therapy. Because of the likelihood of bacterial superinfection and the difficulty in differentiating between bacterial and viral pneumonia, antibiotics should be considered in a more severely ill child. Potential complications include dehydration, local progression of the disease, bronchiolitis obliterans, and apnea (most commonly in the first 3 months of life).²⁵

Mycoplasmal Pneumonia

Mycoplasmal pneumonia accounts for 10 to 20% of all pneumonias and has traditionally been thought to occur most commonly in 5- to 18-year-olds. It is now clear that it also may play a significant role in younger children but is still rare in infants younger than 1 year.²⁵ The onset is classically gradual and insidious, but some patients also may present with abrupt onset of symptoms similar to its bacterial counterpart.⁴ Prodromal symptoms include fever, headache, and malaise, followed several days later by a nonproductive, hacking cough. Patients also may present with pertussis-like illness. Other symptoms of infection may include hoarseness, sore throat, and chest pain; coryza is unusual. Children with mycoplasmal pneumonia generally appear nontoxic. Patients may have rales; wheezing occurs less often. Pharyngitis, cervical lymphadenopathy, conjunctivitis, and otitis media may occur occasionally. Bullous myringitis, although rare, is believed to be indicative of Mycoplasma.²⁵ Rash is present in 10% of patients and may be urticarial, erythema multiforme, maculopapular, or vesicular.²⁶ The course may be complicated by pneumatocele, pleural effusion, pneumothorax, or bronchiectasis. Mycoplasma, typically thought to be a benign and self-limited infection, has been shown to play a significant role in exacerbation of asthma and may cause chronic pulmonary structural abnormalities.⁴

Physical findings generally are less impressive than the radiographic picture; involvement is usually unilateral and in the lower lobes. The radiographic findings are wide ranging, however, and may show lobar consolidation, scattered segmental infiltrates, or interstitial disease. Pleural effusions may occur but are uncommon. The WBC count is usually normal; the erythrocyte sedimentation rate tends to be elevated.

Laboratory diagnosis is problematic. Although it has been used in the past, bedside cold agglutination testing is a poor indication of infection, especially in patients younger than 12 years, and is rarely used today.²⁵ Infection often is diagnosed clinically and treated empirically. Diagnosis may be confirmed with acute and convalescent antibody titers; however, patients may take 4 to 6 weeks to seroconvert, and some patients may fail to mount an immune response.^4,26 Culture is not routinely available; polymerase chain reaction diagnosis at this time is available only from research laboratories.⁴ Complications are varied but unusual and include hemolytic anemia, myopericarditis, neurologic disease (meningoencephalitis, Guillain-Barré syndrome, transverse myelitis, cranial neuropathy), rhabdomyolysis, arthritis, and rash.

Chlamydial Pneumonia

C. trachomatis is a common sexually transmitted organism causing cervical infection in 2 to 30% of pregnant women.⁸ It can be transmitted from the genital tract of infected mothers to their newborn infants, resulting in conjunctivitis in 22 to 44% and pneumonia in 5 to 20%.⁸ An infant with pneumonia caused by C. trachomatis presents at 3 to 19 weeks of age after colonization with the organism at birth. The illness usually begins with nasal congestion followed by cough. In half of the cases, conjunctivitis precedes the onset of respiratory symptoms. The infant is often afebrile and alert but tachypneic, with a repetitive staccato cough that may interfere with feeding or sleeping. It can resemble the paroxysms of pertussis and occasionally precipitates episodes of alarming respiratory distress. Mild retractions and diffuse inspiratory crepitant rales are noted on chest examination; expiratory wheezing is usually absent or minimal. Middle ear abnormalities are present in half of the cases.

The radiograph usually shows hyperinflation with bilateral and symmetrical diffuse interstitial infiltrates (Fig. 170-3). The total WBC count is usually normal but often with an eosinophilia of more than 400/mm³.⁸ Definitive diagnosis is made by isolation of the organism in the tissue culture specimen; diagnostic tests based on polymerase chain reaction are more sensitive than fluorescent antibody stain or tissue culture but may not be as specific. Although it is often a mild illness, chlamydial pneumonia may be complicated by apnea and hypoxemia. Treatment with erythromycin may shorten the course; however, the disease tends to be protracted, with cough and tachypnea often requiring weeks to clear despite the administration of antibiotics.

C. pneumoniae is a species of Chlamydia that is antigenically, genetically, and morphologically distinct from other Chlamydia species. C. pneumoniae infection is readily transmitted from person to person. C. pneumoniae may play a role in respiratory tract infections in infants and young children and may cause mild illness or asymptomatic infection in children and adults. Like Mycoplasma, C. pneumoniae may play a much greater role in pediatric pneumonia than was previously thought. It also commonly may be present as a mixed bacterial infection.⁴ C. pneumoniae has been reported to cause sore throat, fever, headache, pertussis-like cough, pneumonia, and influenza-like illness.²⁷ Outbreaks have been reported in schools, daycare centers, military camps, adolescents, and families.²⁸ Infection with C. pneumoniae can trigger acute episodes of wheezing in children with asthma.

Pertussis

Pertussis, or whooping cough, is a respiratory tract infection seen most commonly in infants younger than 6 months (38% of cases are in children younger than 6 months, and 71% of cases are in children younger than 5 years). The incidence of pertussis increased in the 1980s and 1990s, especially in adolescents and adults, despite high immunization rates.²⁸

The disease is characterized by three clinical stages: catarrhal stage, paroxysmal stage, and convalescent stage.¹² In infants, the disease begins with mild upper respiratory tract symptoms and cough; this catarrhal stage usually lasts 1 to 2 weeks. The disease progresses to severe paroxysms of a staccato cough, followed by post-tussive emesis, and may be accompanied by periods of cyanosis and apnea in infants younger than 6 months.⁶ Classic whoop is rare, occurring in only 6% of patients, and is generally seen in children older than 2 to 3 years. Fever is often absent, and the examination findings are remarkably normal between paroxysms. The paroxysmal stage lasts 2 to 4 weeks and is followed by a convalescent stage, during which symptoms gradually wane. The duration of the illness in more complicated cases may be 6 to 10 weeks.⁶

Immunization is only 80% effective in providing immunity after three doses. Pertussis still must be considered in an immunized infant, although the illness may be mild.¹² The WBC count is usually elevated, exceeding 15,000/mm³ and occasionally 40,000/mm³, with a marked lymphocytosis, although this finding may not be present in infants younger than 3 to 6 months. The chest radiograph may show a “shaggy” right-sided heart border or have clear lung fields. The organism is most easily recovered in the catarrhal or early paroxysmal stages and is rarely found after the fourth week of illness.¹² B. pertussis can be cultured from nasopharyngeal secretions. Cultures may be negative during the first week or after the fourth week of illness in immunized patients or patients treated with antibiotics.¹² Direct fluorescent antibody staining may be used, but this test has low specificity and variable sensitivity.¹² Diagnosis made by direct fluorescent antibody should be confirmed by culture.

Polymerase chain reaction is overall more sensitive and specific. Pertussis is a particularly severe disease in the first year of life; complications are common and include apneic episodes, seizures, secondary bacterial pneumonia, encephalopathy, and death. Pertussis has been increasing in incidence among immunized children and young adults who have waning immunity.⁵ Adults are believed to be a significant source for the disease within the community. The illness in these patients does not follow the classic stages as described here. These patients have a mild but prolonged course. A dry cough is the predominant symptom, often lasting 3 weeks or more. Because of the risk of apnea, all children younger than 6 months with presumed pertussis should be observed in the hospital for monitoring and supportive care and should be treated with erythromycin. Other macrolides and trimethoprim-sulfamethoxazole are possible alternatives.¹² Antimicrobials have no effect on the disease progression after the paroxysmal stage is established but may be beneficial because they limit the spread of organisms. Vaccination of health care workers and the adult population in general with Tdap has been shown to decrease rates of pertussis in infants.⁸

Aspiration Pneumonia

Aspiration pneumonia may be due to mechanical, chemical, or bacterial causes. Bacterial aspiration occurs in children with anatomic abnormalities and central nervous system disturbances that impair normal swallowing or protective airway reflexes. Pulmonary damage results from chemical (e.g., stomach acid) and bacterial (gastrointestinal and upper respiratory organisms) insults. Within several hours of the aspiration, the child may have the onset of cough, tachypnea, and fever. Physical examination commonly reveals rales and wheezing with cyanosis as the disease progresses. Radiographic findings include localized (right middle lobe, right lower lobe) and diffuse infiltrates, which are often bilateral.

Pneumonia in an Immunocompromised Host

Children with chronic disease and congenital, acquired, and iatrogenic immune deficiencies are susceptible to the aforementioned respiratory pathogens and to a multitude of opportunistic organisms, including P. jiroveci, CMV, and fungi. Presenting symptoms may be similar to those in normal hosts; however, the course tends to be more rapid, severe, and fulminant. Rigorous attempts to identify a pathogen are warranted, and patients should be hospitalized for this investigation and to await the results of cultures for monitoring, supportive therapy, and treatment with intravenous antibiotics active against a broad spectrum of organisms. If the patient fails to improve after initial therapy, it is necessary to obtain tissue for diagnosis of potentially treatable organisms.

Laboratory Studies

Any child with pneumonia is at risk for hypoxemia and should have pulse oximetry to determine oxygen saturation. An arterial blood gas study is not needed in most patients but may be considered in a child with severe respiratory distress; it may be useful in following the effectiveness of respiratory status or ventilation. Serum electrolytes, blood urea nitrogen, and creatinine are useful in assessing the degree of dehydration and guiding fluid management when clinically relevant.

Further laboratory studies are obtained only as warranted to help identify the disease process and potential complications. The leukocyte count may be useful in differentiating causes of pneumonia; peripheral WBC counts greater than 15,000/mm³, with predominance of mature and immature granulocytes, suggest bacterial infection; pneumococcal pneumonia typically produces the highest WBC counts.³⁰ Marked leukocytosis and toxic granulation of WBCs also may help identify a child at risk for bacteremia and its potential complications. Normal to elevated WBC counts with lymphocytosis may be seen in viral infections, and eosinophilia suggests chlamydial disease. Increased WBC counts with extreme lymphocytosis typically are associated with pertussis, but this hematologic finding may be absent in infants younger than 6 months. Blood cultures may grow pathogens in only 1 to 10% of cases of bacterial pneumonia. Unfortunately, the contamination rate at most hospitals for cultures is in this range as well. In a well-appearing child with an uncomplicated pneumonia, blood culture is unlikely to be helpful.^1,31 When a blood culture is positive, however, it identifies the specific pathogen, and blood culture should be considered in an ill patient in whom hospitalization with bacterial pneumonia is likely. Sputum cultures may be useful in adolescents but are technically difficult and not useful in younger children.^32,33

Patients with pleural effusions should have lateral decubitus radiographs to assess effusion size and loculation. Computed tomography scan is useful to provide greater detail of effusions and lung abnormalities in critically ill children with complicated pneumonia.³⁴ Routine computed tomography to establish the diagnosis is not recommended. Patients with significant effusions should have thoracentesis for diagnostic and therapeutic purposes. Although parapneumonic effusions are most suggestive of bacterial infection, they also occur with mycoplasmal and occasionally with viral infections.³⁵ The fluid should be sent for Gram’s stain and culture (anaerobic and aerobic bacterial), cell count and differential, total protein level, pH, and glucose concentration. Interpretation of pleural fluid in children follows adult guidelines (see Chapters 76 and 77). Cultures for rare pathogens may be considered if initial assessment is not diagnostic. Bronchoscopy with bronchoalveolar lavage may be useful in a severely ill child.

Nasopharyngeal viral cultures, antigen detection for specific viral or bacterial agents, and serum antibodies for specific agents may be helpful in determining certain etiologic agents. Although most pediatric patients with tuberculosis do not have pulmonary symptoms, skin testing for tuberculosis should be considered for patients with lobar pneumonia, pulmonary effusions, or hilar adenopathy, especially in immunocompromised children or children who have recently immigrated from less developed countries. Acid-fast bacilli often may be shown on an early morning gastric aspirate.³⁶ Sputum specimens generally are not helpful in a child younger than 8 years because of contamination by organisms of the upper respiratory tract.

Bacterial cultures of upper respiratory secretions are of no value and usually grow either normal flora or organisms that reflect only colonization. Although transtracheal sampling and direct aspiration from the lung may permit a more precise diagnosis, the invasiveness of these tests limits their usefulness. Evaluation of potential additional infectious foci should be guided clinically with particular attention to the meninges, pericardium, epiglottis, soft tissue, and joints to identify the offending pathogen and to delineate the disease process fully.

Radiology

A chest radiograph may be obtained to confirm or to rule out an infiltrate. Rarely, a dehydrated child with pneumonia may have a normal study, and once the child is rehydrated, the infiltrate becomes readily apparent. The radiograph also may provide clues to the underlying disease process. Although great variability exists, bacterial pathogens classically produce alveolar infiltrates in a lobar distribution but may produce diffuse interstitial infiltrates.³⁷ Viral and chlamydial infections tend to appear as diffuse interstitial infiltrates, commonly with hyperinflation and atelectasis. Chest radiographs also identify multilobar disease, pleural effusions, pneumatoceles, and pneumothorax (Fig. 170-4). Hilar adenopathy may indicate tuberculosis or malignant neoplasm.

Children without comorbid conditions, who are without fever, unilateral wheezing, or tachypnea, are unlikely to have pneumonia and a chest radiograph is unnecessary. Further, a Cochrane review demonstrated that for non–ill-appearing children with fewer than 14 days of symptoms and clinical signs of pneumonia, chest radiography does not reduce subsequent hospitalization rates or duration of symptoms.38,39 Routine chest radiography is not beneficial in these ambulatory children older than 2 months with acute lower respiratory infections.³⁹

Infants Younger Than 2 Months

Treatment of pneumonia in a pediatric patient consists of appropriate antimicrobial use and supportive therapy (see Table 170-1). Because of the difficulty in identifying an etiologic agent, antibiotic choice is generally empirical. The three most important factors in directing management are the patient’s age, likely pathogen, and degree of illness. An infant younger than 2 months with pneumonia should usually be admitted to the hospital. This age group is immunologically immature, and signs of sepsis may be subtle. Blood, urine, and cerebrospinal fluid cultures generally are indicated before initiation of antibiotics. Ampicillin plus an aminoglycoside or ampicillin and a third-generation cephalosporin would be appropriate initial antibiotic choices for an infant younger than 1 month (although ceftriaxone is contraindicated in infants younger than 1 month).

Infants 2 to 3 Months of Age

In an infant 2 to 3 months old, blood and urine cultures are appropriate. The decision to perform a lumbar puncture depends on clinical suspicion of central nervous system infection. Ampicillin and a third-generation cephalosporin are reasonable for an infant 1 to 3 months old. If C. trachomatis or B. pertussis is suspected, the infant also should be treated with erythromycin after appropriate diagnostic samples have been obtained; other macrolides or sulfonamides (trimethoprim-sulfamethoxazole) may be an alternative in older infants and children.¹² Supportive therapy in this age group consists of fever control and intravenous hydration. A trial of inhaled beta-agonists or racemic epinephrine may be indicated if the patient is wheezing or in significant respiratory distress; supplemental oxygen and respiratory support should be provided as needed. All infants should be monitored with continuous pulse oximetry because apnea and respiratory failure may be precipitous.

Infants and Children Older Than 3 Months

In an older child, pneumonia should be categorized into likely bacterial, viral, or mycoplasmal disease, if possible. Because no single pathognomonic test exists to differentiate bacterial from viral infection, the physician should base the presumptive etiologic diagnosis on clinical, radiographic, and laboratory findings. Although the categorization is not always clear, a toxic child with high fever, lobar consolidation, and leukocytosis is likely to have a bacterial process, whereas a child with a disease of gradual onset, low-grade fever, and interstitial infiltrate with air trapping is more likely to have a viral process.

If a viral agent is suspected and the child is not ill, antibiotics should be withheld. Uncomplicated bacterial pneumonia in immunocompetent children is safe to treat as an outpatient disease. A well-appearing infant or preschool-age child with isolated pneumonia may be treated with oral antibiotics on an outpatient basis. In an infant beyond the neonatal period or a preschool-age child, amoxicillin and amoxicillin–clavulanic acid are considered appropriate first-line agents. Cefuroxime axetil or high-dose amoxicillin (80-100 mg/kg/day) may be used when resistant S. pneumoniae is suspected. Azithromycin is considered an appropriate first-line oral agent in this age group by some researchers.1,33 One study of the treatment of pediatric community-acquired pneumonia showed no difference in clinical cure rate when azithromycin, erythromycin estolate, and amoxicillin–clavulanic acid were compared.⁴¹ A macrolide is the first-line antibiotic choice in a school-age child or adolescent, in whom M. pneumoniae and C. pneumoniae are more common. Every child with bacterial pneumonia treated as an outpatient should be reevaluated within 24 to 48 hours. Patients who are not afebrile, clinically improved, and well hydrated should be evaluated at this time for possible admission to the hospital for parenteral antibiotic therapy. For patients in whom signs of bacteremia are present, a single dose of intramuscular ceftriaxone followed by outpatient oral therapy is recommended. In these cases, close follow-up monitoring is crucial.

For a patient who is admitted to the hospital, intravenous therapy with cefuroxime, cefotaxime, or ceftriaxone is appropriate. Addition of a macrolide should be considered if M. pneumoniae is a possible etiologic agent. Vancomycin should be added if methicillin-resistant S. aureus is suspected.13,23 If an organism has been identified, an antibiotic with a more specific spectrum might be indicated.

Since the 1980s, S. pneumoniae has been developing increasing resistance to penicillin and other antibiotics; in general, this has not been clinically relevant because higher doses overcome the relative resistance. Clinical outcomes with intermediate resistance levels seem to be unchanged.⁴² These patients still respond to penicillin and the cephalosporins at higher doses. If the patient does not respond clinically after a trial of these agents or if the patient is critically ill, use of vancomycin with or without rifampin is recommended.⁴³

Supportive therapy includes hydration and fever control with antipyretics. Appropriate laboratory testing should be performed to attempt identification of more virulent pathogens. The child should be examined for development of an additional infectious focus, and a repeated radiograph may be considered to determine spread or development of a pleural effusion.

Indications for hospitalization at the time of diagnosis include toxic appearance, vomiting or dehydration, respiratory compromise (distress, hypoxia, or inadequate ventilation), multilobar disease, pleural effusions, impaired immune function, and unstable social environments. Strong consideration should be given to hospitalization of children younger than 6 months because they are prone to complications of bacterial pneumonia more than older children are. Supportive therapy for the inpatient should include maintenance of fluid and electrolyte balance and fever control, supplemental oxygen, inhaled bronchodilators, ventilatory assistance, and pleural fluid drainage as indicated. Parenteral antibiotic therapy should be administered until clinical improvement occurs. Other factors that influence duration of parenteral antibiotic treatment include the age of the patient, specific pathogen, presence of bacteremia, and any additional infectious foci.

A trial of bronchodilators may be worthwhile (aerosolized beta₂-adrenergic agent) even in the absence of wheezing and should be considered in a patient with respiratory distress. Although this treatment is not always successful, if the child responds with diminished wheezing, improved aeration, or reduced work of breathing, one may continue with nebulized bronchodilators.

Children with neurologic or anatomic abnormalities who aspirate oral or gastric contents are susceptible to pneumonia predominantly from anaerobes. Penicillin and clindamycin are appropriate first-line antibiotic choices. In seriously ill patients or patients not responding to the first-line treatments, agents such as chloramphenicol, metronidazole, and cefoxitin may be more useful. Nosocomial infections should be treated with antibiotics also active against aerobes and gram-negative bacilli. Children with significant aspiration should be admitted to the hospital, and supportive therapy should include hydration, supplemental oxygen, oropharyngeal suctioning, and intubation of the trachea if airway reflexes are impaired or respiratory failure is manifested.

Long-term management of a child with pneumonia should include a clinical reevaluation 2 to 3 weeks after diagnosis. If the child had a prompt response to therapy and is entirely well at follow-up evaluation with a normal physical examination, a repeated radiograph is unnecessary.⁴⁴ If the child has undergone a complicated disease course (e.g., pleural effusion), has residual symptoms, or manifests any abnormality on examination or if the illness is not the child’s first episode of pneumonia, a chest radiograph should be obtained to ensure complete resolution of the disease. The follow-up radiograph should be performed 6 to 8 weeks after diagnosis.

In management of a child with pneumonia, it is essential to consider the age and clinical presentation of the child in delineating specific etiologic agents. Common pathogens may be treated as an outpatient disease in nontoxic patients; infants and children who exhibit some respiratory compromise may require parenteral antibiotics, support, and hospitalization. During the past several years, the patterns of etiologic organisms have been changing. The spectrum of antimicrobial sensitivities also has changed, particularly with the emergence of penicillin-resistant S. pneumoniae. Repeated chest radiographs are indicated in children who fail to respond to a course of treatment; immunocompetent patients who respond to therapy may be observed clinically, and a repeated chest radiograph is not necessary to document cure.

Perspective

CF is an autosomal recessive disease caused by a mutation in the CF transmembrane conductance regulator (CTFR) gene. In whites, approximately 1 in 25 is a carrier, and the disease has an incidence of 1 in 2500 births.⁴⁴ The disease also is present (in decreasing incidence) in Hispanics, Native Americans, African Americans, and Asians. Progressive lung disease and infection account for most of the morbidity and nearly all of the mortality in CF. Defects in chloride transport across the airway epithelium result in reduced ciliary clearance of thickened mucus, decreased antimicrobial effect of the airway surface, increased bacterial adherence, and innate secretion of inflammatory cytokines. All of these factors result in a unique sensitivity to bacterial infection of the airway.^45,46

Diagnostic Strategies

Chest radiographic findings of CF include emphysema, peribronchial thickening, bronchiectasis, and focal infiltration, which may be linear or nodular in nature (Fig. 170-5). Crucial to the effective treatment of pulmonary infections in CF patients is the identification of pathogens involved, usually through sputum culture. Early childhood pneumonias in patients with CF are predominantly caused by S. aureus and H. influenzae.

Management

With the emergence of methicillin-resistant S. aureus, careful attention should be paid to antibiotic coverage. Patients receiving antistaphylococcal prophylaxis may be at increased risk for pseudomonal infections.⁴⁴ There is emerging evidence that CF patients also are at increased risk for hospitalization with nonbacterial pathogens.⁴⁷

By 18 years of age, 80% of patients are colonized with P. aeruginosa. When colonization is established, it is generally considered permanent.⁴⁸ Acute infective exacerbations generally are managed by oral and intravenous antimicrobial drugs, typically a penicillin (e.g., ticarcillin or piperacillin) or ceftazidime combined with an aminoglycoside for purposes of synergy.⁵ If a patient’s previous sputum culture result is available, care should be taken to ensure coverage of the last known bacterial pathogens. Resistant strains may benefit from imipenem or meropenem. Patients routinely are hospitalized for 10 to 14 days for the course of therapy.⁴⁴

Burkholderia cepacia, a significant pathogen in CF patients, has been associated with an accelerated decline in clinical status and increased mortality. In general, antimicrobial coverage is similar to that for Pseudomonas. Resistance is common, however, and the existence of differing colonization and resistance patterns of patients with CF necessitates respiratory isolation from other susceptible individuals.⁴⁹

Clearance of thick mucoid secretions is vital for treatment. Patients may respond favorably to bronchodilator therapy and to mucolytics, such as inhaled N-acetylcysteine, in the acute setting.⁵⁰ Chest physiotherapy often is provided by a high-frequency oscillator device. A flutter valve or a positive expiratory pressure mask also may be of assistance for improved mucoid clearance. Short-term control of inflammation may be obtained by inhaled corticosteroids.⁵¹