Most pediatric pulmonary parenchymal disease occurs as a result of an infectious agent.
Clinical evaluation for parenchymal lung disease in the pediatric patient should include a search for symptoms and signs associated with pulmonary disease, such as difficulty with feeding, exercise intolerance, chest pain, cough, tachypnea, dyspnea, cyanosis, orthopnea, clubbing of the nail beds, weight loss, and lethargy.
Factors predisposing a child to bacterial pneumonia include having numerous siblings, smoke exposure, preterm delivery, living in an urban environment, poor socioeconomic status, presence of an airway foreign body, impaired immune response, congenital and anatomic lung defects, abnormalities of the tracheobronchial tree, cystic fibrosis, and congestive heart failure.
Viral agents are the leading cause of lower respiratory tract infection in infants and children.
Three major clinical syndromes are associated with lower respiratory tract viral illnesses: (1) bronchitis, (2) bronchiolitis, and (3) pneumonia.
Fungal infections are important in the differential diagnosis of pulmonary infections, particularly in children whose immunity is compromised and in healthy children who are exposed to pathogens in a particular geographic or environmental setting.
Three forms of disease patterns in pneumocystosis are (1) childhood/adult, (2) infantile, and (3) chronic fibrosing, the last observed in some patients infected with the human immunodeficiency virus.
Chemical pneumonitis and/or pneumonia may be acquired by (1) aspiration, (2) inhalation, (3) ingestion, or (4) injection.
Pulmonary hemorrhage is a potentially life-threatening event that can occur at any age. Clinical presentation varies from massive fatal hemoptysis to silent bleeding with respiratory distress and anemia.
Pneumonitis, or inflammation of the lung parenchyma, is perhaps the most common cause of life-threatening lower respiratory tract disease in pediatric patients. Although pneumonitis may result from noninfectious processes ( Box 52.1 ), most pediatric pulmonary parenchymal disease occurs as the result of an infectious agent. Pneumonitis may involve the pleura, interstitium, and airways; pneumonia, by definition, must include alveolar consolidation. Whereas early parenchymal lung injury is associated with increased cellularity with minimal fibrosis, advanced disease is characterized by extensive fibrosis and destruction of gas-exchange units. Physiologic changes may include the following: low lung volumes, diminished lung compliance, impaired gas exchange, and airflow limitation. This chapter addresses the principal potential causes of pediatric pulmonary parenchymal disease, including alveolar and interstitial disorders.
Acute lung injury
Mixed connective tissue disorders
Idiopathic pulmonary fibrosis
Pulmonary hemorrhage syndromes
Pulmonary venoocclusive disease
Desquamative interstitial pneumonia
Lymphocytic infiltrative disorders
Lymphocytic interstitial pneumonitis
Familial erythrophagocytic lymphohistiocytosis
Regardless of the cause, pneumonitis often follows a common pathogenesis. The initial parenchymal injury can result from mechanisms that directly damage the endothelium or epithelial cells. Other agents may injure the lung indirectly by one or more of the following processes:
Generation of toxic radicals
Recruitment of inflammatory cells (e.g., neutrophils)
Activation of complement and/or release of chemotactic factors
If these processes go unchecked, alterations may occur in the lung parenchyma and connective tissues, leading to end-stage fibrosis. This condition is characterized by destruction of gas-exchange units and airways and the development of parenchymal cystic lesions.
Changes in lung volumes in pulmonary parenchymal disease depend primarily on the intensity of the alveolitis and stage of the disease process. Acute severe pneumonitis with intense alveolitis is characterized by moderate to severe reduction in both vital capacity (VC) and total lung capacity. It is also associated with a reduction in pulmonary compliance. In the early stages, patients with chronic interstitial diseases involving the lung parenchyma often have normal VC and total lung capacity. Subsequent reduction in lung volumes and pulmonary compliance occurs as the disease progresses, leading to pulmonary fibrosis. Expiratory flow rates are usually preserved in persons with pneumonitis involving the lung parenchyma, and major obstructive defects, although reported, are rare. Diffusion capacity, one of the earliest and most sensitive tests of parenchymal inflammation, is diminished in persons with interstitial lung disease (ILD). A reduction in diffusion capacity is not specific and may be found with other parenchymal disorders. Early in the course of parenchymal disease, resting arterial oxygen tension may be normal, but there is often mild alveolar hyperventilation with reduction in alveolar carbon dioxide tension and widening of the alveolar-arterial oxygen gradients (P ao 2 – Pa o 2 ). With exercise, hypoxemia and an increased P ao 2 – Pa o 2 become exaggerated because of ventilation/perfusion (V/Q) imbalance. V/Q mismatch is attributed to regional alterations of flow, altered parenchymal compliance, and increased obstruction to pulmonary airflow. Progressive alveolitis and subsequent derangement of gas exchange lead to deterioration of ventilatory efficiency and markedly increased work of breathing. Adequate oxygenation may become impossible even with the use of high-flow supplemental oxygen. Resting hypercapnia, pulmonary hypertension, and eventual right ventricular dysfunction with heart failure are common sequelae.
Diagnosing parenchymal lung disease in the pediatric patient may be quite challenging because of extreme variability in the presentation of disease. Clinical evaluation of the child should include a search for symptoms and signs associated with pulmonary disease, such as difficulty with feeding, exercise intolerance, chest pain, cough, tachypnea, dyspnea, cyanosis, orthopnea, clubbing of the nail beds, weight loss, and lethargy. In the child with diffuse alveolar disease, auscultative findings may be normal unless significant consolidation or small airway involvement is present. Fine crackles that may be heard throughout the chest late in inspiration are a characteristic finding of small airway disease. These rales are produced by the opening of occluded small peripheral airways.
The chest radiograph is critical in the diagnosis and management of pulmonary parenchymal disease. In children with ILD the classic radiographic features that are present in adults may be absent. Computed tomography scanning, gallium lung scanning, and bronchoalveolar lavage (BAL) are useful techniques in the diagnosis and management of diseases involving the lung parenchyma. Pulmonary function testing is important and usually can be performed reliably in children who are older than 4 years. ,
Bacterial infections of the lower respiratory tract continue to account for a significant number of hospital admissions. The frequency of bacteria as etiologic agents of lower respiratory tract infection varies from 10% to 50% depending on the study population and methods of evaluation used. , In a large study of pediatric patients with lower respiratory tract infections, an etiologic agent was identified in nearly 50% of the patients. Bacteria accounted for 10% to 15% of the causative agents identified.
Factors predisposing to bacterial pneumonia include having numerous siblings, smoke exposure, preterm delivery, living in an urban environment, and poor socioeconomic status. Hospitalization also increases the risk of contracting bacterial pneumonia because of the clustering of ill patients in confined areas, administration of immunosuppressive therapy, and various medical and surgical interventions that enhance the opportunity for colonization and infection. Additional factors that increase susceptibility to bacterial pneumonia include the presence of an airway foreign body, impaired immune response, congenital and anatomic lung defects, abnormalities of the tracheobronchial tree, cystic fibrosis, and congestive heart failure.
Bacterial pneumonia is an inflammatory process of the lungs that may involve interstitial tissue and pleura in its evolution but always progresses to alveolar consolidation.
Pneumonia occurs when pulmonary defense mechanisms are disrupted and bacteria invade the respiratory system by aspiration or hematogenous spread. In most instances pneumonia appears to be a consequence of aspiration of a high inoculum of pathogenic bacteria. Viruses are often responsible for enhancing the susceptibility of the respiratory tract to bacterial infection. Less frequently, bacterial pneumonia may be the result of defects in host immunity because of young age, underlying immune dysfunction, or immunosuppressive therapy. Pneumonia may also occur when host defenses are mechanically disrupted because of tracheostomy or endotracheal intubation. The presence of respiratory pathogens in the terminal bronchioles and alveoli induces an outpouring of edema fluid and large numbers of leukocytes into the alveoli. , Macrophages subsequently remove cellular and bacterial debris. The infectious process may extend further within the lung segment or disseminate through infected bronchial fluid to other areas of the lung. The pulmonary lymphatic system enables bacteria to reach the bloodstream or visceral pleura.
With the consolidation of lung tissue, VC and lung compliance markedly decrease. This leads to intrapulmonary right-to-left shunt and V/Q mismatch, resulting in hypoxia. Subsequently, pulmonary hypertension may develop because of significant oxygen desaturation and hypercapnia, often leading to cardiac overload.
Signs and symptoms of bacterial pneumonia vary with the individual pathogen, age and immunologic condition of the patient, and severity of the illness. Clinical manifestations, especially in newborns and infants, may be absent. General or nonspecific complaints include fever, chills, headache, irritability, and restlessness. Individual patients may have gastrointestinal complaints, including nausea, vomiting, diarrhea, abdominal distention, or pain. Specific pulmonary signs include nasal flaring, retractions, tachypnea, dyspnea, and, occasionally, apnea.
Tachypnea is the most sensitive index of disease severity. The sleeping respiratory rate is often a valuable guide to diagnosis. On auscultation, diminished breath sounds are frequently noted. Fine crackles that may be heard in children and older patients are commonly absent in infants. Because of the relatively small size of the child’s thorax and thin chest wall, broad transmission of breath sounds occurs, and the classic findings of consolidation are often obscured. Pleural inflammation may be accompanied by chest pain at the site of inflammation. This pleuritic pain may cause “splinting,” which restricts chest wall movement during inspiration and reduces lung volume.
Extrapulmonary infections that may be present in some children include abscesses of the skin or soft tissue ( Staphylococcus aureus ); conjunctivitis, sinusitis, otitis media, and meningitis ( Streptococcus pneumoniae or Haemophilus influenzae ); and epiglottitis ( H. influenzae ).
Bacterial pneumonia is typically characterized by defined areas of consolidation with either segmental or lobar involvement. Lobar consolidation is the most characteristic, but multilobed disease is not unusual. The findings of pleural effusion, pneumatocele, or abscess are also strongly indicative of a bacterial infection. Staphylococcal pneumonia is suggested by the rapid clinical and radiographic progression of disease, particularly in a young infant. Evidence of an abscess or pneumatocele further suggests a diagnosis of staphylococcal or gram-negative pneumonia, such as Klebsiella. Group A streptococcal pneumonia may initially present with a diffuse interstitial pattern before the development of consolidation. Except for Pseudomonas , which may have a diffuse nodular appearance in the lower lobes, pneumonias caused by gram-negative organisms have no specific radiographic pattern. Anaerobic pulmonary infection is also associated with lung abscesses and air-fluid levels.
Bacterial pneumonia is suggested by fever, leukocytosis (>15,000 white blood cells), and increased band forms on the peripheral blood smear. Examination of the sputum may be helpful in establishing the diagnosis of bacterial pneumonia; however, it is often difficult to obtain a satisfactory sputum sample in pediatric patients unless transtracheal aspiration or bronchoscopy is used. Transtracheal aspiration, although useful in adolescents and adults, is associated with significant complications in infants and young children. If a sputum sample is obtained (an adequate specimen must have more than 25 polymorphonuclear cells and fewer than 25 epithelial cells per high-power field), the Gram stain should be examined for a predominant bacterial pathogen and cultures should be performed with the appropriate antibiotic susceptibility studies. Bacterial pneumonia is accompanied by bacteremia in a significant number of cases; hence, blood cultures should be obtained before initiation of antibiotic therapy. Circulating antigens in S. pneumoniae and H. influenzae may be detected in the blood with counterimmune electrophoresis (CIE), polymerase chain reaction (PCR), or latex agglutination. ,
If a significant pleural effusion is present, a diagnostic thoracentesis should be performed for the purposes of Gram stain and culture. Culturing pleural fluid has a relatively high yield in patients who have not received previous antibiotic therapy. If the Gram stain of pleural fluid is negative, CIE or latex agglutination should be performed because bacterial antigen may be detected in the fluid even after the initiation of antibiotics.
BAL should be considered in the management of a severely ill child in order to make a prompt diagnosis. , Making a prompt diagnosis is essential for the patient with progressive disease who has responded poorly to initial therapy or for the child with underlying immunodeficiency for whom empiric antibiotic treatment may be hazardous. In such instances, if the BAL is nondiagnostic, then lung aspiration or biopsy should be considered. Material may be obtained through closed-needle biopsy, percutaneous needle aspiration, or an open-lung biopsy. Positive results for such procedures in carefully selected cases identify an etiologic agent in 30% to 75% of cases, with open-lung biopsy having the highest yield. ,
Group B streptococci
Group B streptococci can cause infection in people of any age; however, these organisms are common pathogens in infants younger than 3 months. Early-onset illness is often associated with maternal fever at the time of delivery, prolonged rupture of membranes, amnionitis, prematurity, and low birth weight.
Infected neonates usually manifest clinical symptoms within the first 6 to 12 hours of life. Symptoms include fever, respiratory distress, apnea, tachypnea, and hypoxemia. By 12 to 24 hours of age, signs of cardiovascular collapse are often apparent. Frequently, the syndrome of pulmonary hypertension of the newborn is present, and pulmonary or intracranial hemorrhage may become the terminal event.
Isolation of the organism establishes the diagnosis. Cultures from blood and cerebrospinal fluids must be obtained in all instances of suspected group B streptococcal pneumonia. Rapid diagnostic techniques have been helpful in providing early diagnoses. The radiographic findings in neonates with group B streptococcal pneumonia can be either a lobar (40%) or a diffuse reticulonodular pattern with bronchograms similar to findings of respiratory distress syndrome.
Aggressive cardiovascular and ventilatory support is usually required, particularly in the early stages of the disease. Antibiotic therapy should include a combination of ampicillin or penicillin and an aminoglycoside agent.
Although in the past the mortality rate of patients with group B streptococcal pneumonia could be as high as 50% to 60%, recent studies suggest improvement with prompt initiation of therapy and even better outcomes with maternal prophylaxis. Some infants experience a second episode of infection 1 to 2 weeks after discontinuation of antibiotic therapy. Infants with group B streptococcal pneumonia and meningeal involvement (30%) may demonstrate significant neurologic deficits (20%–50%).
S. pneumoniae is a gram-positive diplococcus with at least 84 sera types; however, 80% of the serious infections are caused by only 12 sera types. Streptococci are a major cause of pneumonia in the United States, usually affecting infants younger than 2 years, with a peak age between 3 and 5 months. Patients with asplenia, functional hyposplenia, or malignancy or those receiving immunosuppressive drugs are at special risk of the development of invasive disease.
The radiographic finding in infants is often a patchy bronchopneumonia. Lobar consolidation is not uncommon. Penicillin is the drug of choice in the treatment of persons with streptococcal pneumonia. However, organisms relatively resistant to penicillin occur in 3% to 40% of culture-positive patients recorded in studies from different parts of the United States. In such instances pneumonias have been effectively treated with vancomycin or high-dose β-lactam cephalosporin agents, such as cefuroxime, ceftriaxone, or cefotaxime. Disease resulting from penicillin-resistant pneumococci should be considered in patients who received therapy with β-lactam antibiotics.
The pneumococcal 13-valent conjugate vaccine is recommended for all children aged 5 years and younger. It is also recommended for certain children aged 60 to 71 months with chronic medical conditions, immunosuppressive conditions, functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants. The pneumococcal polysaccharide vaccine, a 23-valent formulation, is recommended in children 2 years and older with an increased risk of invasive pneumococcal disease.
Haemophilus organisms are small, nonmotile, gram-negative rods that occur in both encapsulated and nonencapsulated forms. Approximately 90% to 95% of invasive disease is caused by the encapsulated sera type B. A pleural effusion or empyema is detected in nearly 40% of patients with H. influenzae pneumonia. There is an extremely high incidence of bacteremia in this disease. Serious complications—such as epiglottitis, meningitis, and pericarditis—can be diagnosed in 15% to 20% of patients. Cellulitis, anemia, and septic arthritis occur infrequently.
In a hospitalized patient, administration of β-lactam agents or a second- or third-generation cephalosporin is generally an effective therapy. , The mortality rate in appropriately treated patients is generally considered to be less than 5% and often is related to associated meningitis, epiglottitis, or pericarditis rather than the pneumonic process itself. Hib conjugate vaccine is an important measure in reducing the incidence of Haemophilus -related disease and should be administered to all children. , ,
Primary S. aureus pneumonia has decreased in frequency in recent years but still accounts for approximately 25% of cases in young infants. The incidence of secondary or metastatic dissemination has increased since 1972. Patients with primary pneumonia present with fever and respiratory symptoms, whereas those with metastatic disease often present with fever, generalized toxicity, and musculoskeletal symptoms. In patients presenting with primary staphylococcal pneumonia, the disease is often preceded by an upper respiratory tract infection. Pleural effusion or empyema develops in nearly 80% of the patients with primary staphylococcal pneumonia and is extremely common in patients with metastatic disease. It is not unusual for patients with staphylococcal pneumonia to remain bacteremic long after the initiation of appropriate antibiotic therapy.
Radiographic findings of S. aureus pneumonia differ according to the stage of the disease. They vary from minimal changes to consolidation (most common) and are associated with pleural effusion (50%–60%) or pneumothorax (21%). Pneumatoceles usually appear during the convalescent stage and may persist for prolonged periods in asymptomatic patients. Antibiotic therapy should be administered intravenously and include a drug that is resistant to inactivation. Strong consideration should be given to providing antibiotic coverage for methicillin-resistant S. aureus, which can account for 1% to 30% of isolates depending on the prevalence in the area. The duration of therapy is usually lengthier in patients with staphylococcal disease than for patients with other bacterial pneumonias and consists of 21 days or more of treatment. The mortality rate of staphylococcal pneumonia varies from 23% to 33%. Increased mortality is usually associated with younger age, inappropriate initial antimicrobial therapy, or failure to drain an empyema appropriately.
Mycoplasma organisms are the smallest free-living microorganisms. They lack a cell wall and are pleomorphic. Mycoplasma is an uncommon cause of pneumonia in children younger than 5 years but is the leading cause of pneumonia in school-aged children and young adults. Illness can range from a mild upper respiratory tract infection to tracheobronchitis to pneumonia. Symptoms include malaise, low-grade fevers, and headache. In 10% of children a rash develops that usually is maculopapular. Cough, if it develops, usually occurs within a few days and may continue for 3 to 4 weeks. Initially the cough is nonproductive but then may become productive and is usually associated with widespread rales on physical examination. Radiographic abnormalities vary but are usually bilateral and diffuse.
Isolation of Mycoplasma by culture is complicated by the requirement for special enriched broth or agar media, which are not widely available. It is successful in only 40% to 90% of cases and requires 7 to 21 days. A fourfold increase in antibody titer between acute and convalescent sera is diagnostic, but the time involved is lengthy, providing only a retrospective diagnosis. Complement fixation and immunofluorescent and several enzyme immunoassay antibody tests have been developed but are of limited diagnostic value. Serum cold agglutinins with titers of 1 : 32 or greater are present in more than 50% of patients with pneumonia by the beginning of the second week of illness. The PCR test has become an important means of diagnosing M. pneumoniae infections in clinical practice, allowing for initiation of therapy directed at the causative pathogen. Treatment of upper respiratory tract infections or acute bronchitis is rarely indicated, but treatment with erythromycin or another macrolide, such as azithromycin, is indicated for persons with pneumonia or otitis media.
Pneumonia caused by gram-negative enteric bacteria, especially Pseudomonas, is almost always found in patients with underlying pulmonary disease, compromised immune status, or those receiving prolonged respiratory therapy. , Gram-negative enteric bacteria are a frequent cause of nosocomial infection in critical care units. These organisms can produce a severe necrotizing pneumonia that is associated with an increase in morbidity.
Pneumonia caused by Legionella pneumophila has been reported infrequently in the pediatric age group. The onset of this disease is characterized by high, unremitting fever; chills; and a nonproductive cough. Extrapulmonary manifestations include gastrointestinal symptoms such as diarrhea, liver involvement, and confusion. Chest radiographs typically consist of peripheral nodular infiltrates and pleural effusions. Cavitation occurs only in immunosuppressed individuals. Death in the normal host is unusual if prompt therapy with azithromycin or erythromycin is initiated.
Pneumonia resulting from anaerobic upper respiratory flora is uncommon in healthy children. When it does occur, it is frequently associated with risk factors such as underlying pulmonary disease, a central nervous system (CNS) disorder (including seizures), a postanesthetic state, and aspiration of a foreign body. Lung abscess and empyema are frequent complications in persons with anaerobic bacterial pneumonias.
The mortality rate in persons with uncomplicated bacterial pneumonia is less than 1%. Death is more common in children with a complicated disease or an underlying disorder. The most frequent complications of bacterial pneumonia are pleural effusion and empyema ( Table 52.1 ). Thoracentesis should be performed if fluid is present to facilitate an etiologic diagnosis and establish the character of the fluid. Tube thoracostomy is indicated if a large amount of fluid is present and causes respiratory compromise or if purulent fluid is obtained by thoracentesis. Empyema may extend locally to involve the pericardium, mediastinum, or chest wall. Evidence of empyema extension should be considered in the child who is unresponsive to antibiotic therapy.
|Necrotizing pneumonia||Anaerobic, GNB|
|Shock||GBS, SP, H. influenzae , GNB|
|Pneumatoceles||H. influenzae , anaerobic, staph, SP, GAS|
|Abscess (lung)||Staph, SP, anaerobic|
|Pleural effusion||H. influenzae , GAS, SP, staph|
|Empyema||H. influenzae , staph, SP|
|Epiglottitis||H. influenzae , GAS|
|Meningitis||H. influenzae , GBS, SP|
|Bone/joint||H. influenzae , staph|
When tube thoracostomy/surgical drainage is required, it should be discontinued as soon as drainage has substantially decreased. For patients with staphylococcal empyema, streptococcal pneumonia, or H. influenzae empyema, 3 to 7 days of drainage is usually sufficient. Patients with empyema require prolonged antimicrobial therapy and careful follow-up.
Pneumothorax and pneumatoceles can be seen with almost any bacterial pneumonia but are especially common with staphylococcal disease. Such pneumatoceles require no special therapy and usually resolve. Lung abscess is an infrequent complication of H. influenzae and pneumococcal pneumonia and is most often encountered with staphylococcal disease or anaerobic bacteria.
Prognosis is usually excellent, even in persons with severe bacterial pneumonia complicated by empyema. Long-term follow-up of children with empyema has demonstrated remarkably few if any residual pulmonary function abnormalities and remarkable clearing of chest radiographs. In contrast to adults with empyema, children seldom require surgical procedures such as decortication. However, follow-up chest radiographs should be obtained on all patients with bacterial pneumonia to document complete resolution. Such radiographic follow-up studies are probably not indicated until at least 6 to 8 weeks following the initiation of antibiotic therapy.
Therapy for persons with bacterial pneumonia should include appropriate IV antibiotic treatment directed toward the specific pathogen if it is known ( Table 52.2 ). Localized or compartmental complications—such as empyema, lung abscess, pericarditis, or septic joints—require appropriate surgical drainage and antibiotic therapy. Prevention via immunization or chemoprophylaxis has changed the incidence and epidemiology of pneumonitides significantly. Options for immunization, active or passive, and chemoprophylaxis for various etiologic agents are listed in Table 52.3 .
|Serious, life-threatening pneumonia, nonsuppressed host||Cefotaxime or ceftriaxone + azithromycin + vancomycin |
Bronchial lavage or needle aspiration of lung may be necessary to establish diagnosis.
|Suppressed neutropenic host||Imipenem/meropenem or piperacillin or ceftazidime + aminoglycoside ± clindamycin |
Vancomycin not included in initial therapy unless high suspicion or if patient has indwelling line. Amphotericin not used unless still febrile after 3 days/high suspicion. Bronchial lavage, needle/open biopsy may be necessary to establish diagnosis.
|Lung abscess||Clindamycin or ticarcillin/clavulanate or piperacillin/tazobactam|
|Pneumonia With Empyema|
|Streptococcus pneumoniae, group A strep|
|Penicillin susceptible||Preferred: ampicillin or penicillin + chest tube drainage |
Alternative: ceftriaxone or cefotaxime + chest tube drainage
|Penicillin resistant||Preferred: ceftriaxone + chest tube drainage |
Alternative: ampicillin (increased dosing), levofloxacin or linezolid + chest tube drainage
|Methicillin sensitive||Preferred: cefazolin, nafcillin or oxacillin + chest tube drainage |
Alternative: clindamycin or vancomycin + chest tube drainage
|Methicillin resistant||Preferred: vancomycin + chest tube drainage |
Alternative: linezolid + chest tube drainage
|Pneumonia Without Empyema|
|Haemophilus influenzae||Preferred: ampicillin or cefotaxime or ceftriaxone |
Alternative: ciprofloxacin or levofloxacin
|Klebsiella pneumoniae||Meropenem until susceptibilities are available|
|Escherichia coli , Enterobacter||Aminoglycoside or cephalosporin|
|Legionella||Preferred: azithromycin or erythromycin |
Alternative: ciprofloxacin or levofloxacin
|Pseudomonas||Aminoglycoside + anti- Pseudomonas penicillin or aminoglycoside + ceftazidime|
|Mycoplasma pneumoniae||Preferred: azithromycin |
Alternative: erythromycin or levofloxacin
|Cytomegalovirus||IVIG: prophylaxis in seronegative transplant recipients||Ganciclovir or valganciclovir|
|Haemophilus influenzae type B||Capsular polysaccharide vaccine or conjugate vaccine||Cefotaxime or ceftriaxone|
|Influenza||Inactivated virus produced in chicken embryos||Oseltamivir (A or B) or zanamivir (A or B)|
|Measles||Live virus vaccine or IVIG for immunocompromised patients||None|
|Streptococcus pneumoniae||Capsular polysaccharide antigens of 13 or 23 pneumococcal serotypes vaccine or pneumococcal conjugate vaccine||Penicillin VK for functional or anatomic asplenia until age 5 y|
|Pneumocystis carinii||None||Trimethoprim-sulfamethoxazole or pentamidine or dapsone or atovaquone|
|RSV||Palivizumab (monoclonal antibody)||None|
|Group B strep||None||Intrapartum antibiotics|
Infection is the most common cause of pulmonary interstitial disease in children, and viral agents are the leading cause of lower respiratory tract infection in infants and children. The viral agents listed in Table 52.4 account for the greatest percentage of pediatric pulmonary disease. Nearly 85% of all hospitalizations of children younger than 15 years occur during outbreaks of respiratory syncytial, parainfluenza, or influenza virus.
|Respiratory syncytial virus||+++++|
The diagnosis of viral pneumonia in children is frequently based on the clinical presentation, epidemiologic setting, and exclusion of bacterial pathogens by negative cultures. A specific agent is identified in only approximately 50% of cases of presumed viral pneumonia. Pediatric viral respiratory tract infections occur most commonly during the winter, with distinct peaks during midwinter and early spring in temperate climates. Closed population groups provide for greater spread of respiratory viruses and increased recognition of viral pneumonias.
The mechanism of infection for most respiratory viruses appears to be a progressive spread from the larger airways to the alveoli. The respiratory epithelial cell is the major target of cytopathic effect. The normal ciliated columnar epithelium may become markedly dysplastic with loss of the overlying cilia. , Areas of ulceration then occur as segments of the mucosal surface desquamate into the bronchial lumen. Impaired mucociliary clearance occurs, and altered stimulation of nerves mediating bronchial smooth muscle tone leads to increased airway resistance. Enhanced mucus formation along with mucosal debris may lead to obstruction of the bronchioles, luminal narrowing, distal air trapping, and hyperinflation of various lung segments. In advanced disease with complete small airway obstruction, atelectasis results, causing hypoxemia as a result of intrapulmonary shunting and V/Q imbalance.
In persons with severe viral pneumonia, widespread parenchymal injury caused by a necrotizing alveolitis may develop. Alveolar round cell infiltrates often occur, with subsequent hyaline membrane formation and intraalveolar hemorrhage, which produces extensive parenchymal destruction and diminished lung compliance, decreased lung volumes, and intrapulmonary shunting.
Although the clinical presentations of illness by respiratory viruses overlap, presumptive diagnosis of the specific etiology is based on clinical presentation, setting, and, most importantly, epidemiologic information. In the past, virus isolation or seroconversion was necessary for a definitive diagnosis. Today many respiratory viral infections can be diagnosed using new techniques.
Viral specimens should be obtained as early as possible during the period of greatest viral excretion. Cultures may be negative in up to 40% of patients during acute viral respiratory tract disease; failure to isolate a virus is not definitive evidence against the diagnosis of viral pneumonia. Serologic tests—including complement fixation, hemagglutination inhibition, enzyme-linked solid-phase assays (enzyme-linked immunosorbent assays), and antibody assays—have been used in the diagnosis of viral infection. Histologic evidence of infection in biopsy or postmortem specimens may be helpful, particularly when intranuclear inclusions are documented. Rapid diagnostic techniques focus on detection of the virus or its components in the sample. These new techniques include refinements in the use of immunofluorescence, enzyme immunoassay, time-resolved fluoroimmunoassay, latex agglutination assays, and use of nucleic acid hybridization methods, such as DNA probes and PCR.
Three major clinical syndromes are associated with lower respiratory tract viral illness:
Bronchitis: Acute bronchitis is a febrile illness associated with a new productive cough. Symptoms of upper respiratory tract infection may be present. Acute bronchitis can adversely affect respiratory function, particularly in patients with chronic pulmonary impairment, leading to hospitalization of persons with marginal lung function.
Bronchiolitis: Symptoms result from airflow obstruction caused by localized inflammation of the terminal respiratory bronchioles. The development of cough; tachypnea with intercostal retractions; fine, moist, inspiratory crackles; and expiratory wheezes are characteristic. Hypoxemia and cyanosis are often present.
Pneumonia: Primary viral pneumonia is frequently a mild illness characterized by a mild cough and one or more segmental infiltrates on chest radiograph. Although usually a self-limited process, some patients may progress with extensive parenchymal injury, diffuse interstitial alveolar infiltrates, and severe hypoxemia. Bacterial superinfection is heralded by increased temperature, change in sputum, and signs of localized consolidation several days after the initial onset of symptoms.
Differentiation of bacteria from viral pneumonia cannot be made solely on radiographic appearance. Children with presumed viral pneumonia, however, may have several radiographic findings, including the following:
Peribronchial thickening and perihilar linear densities
Partial lobar or patchy involvement in multiple areas of the lung
Shifting regional infiltrates
Areas of hyperinflation and atelectasis
Hilar adenopathy is usually absent. Diffuse bilateral infiltrates similar to those reported in acute respiratory distress syndrome (ARDS) have been found in persons with severe influenza, adenovirus, and respiratory syncytial virus (RSV) pneumonias. Pleural effusions can occur in both adenovirus and parainfluenza pneumonias. Pulmonary calcifications/nodules have been described in the convalescent phase of varicella and measles.
We review the most common viral pathogens that cause pneumonitis in children but have elected to exclude such viruses as hantavirus, which are beyond the scope of this chapter. There continue to be viruses that are identified as pathogens in viral pneumonitis but as of yet do not have effective chemoprophylaxis or therapy, such as the human metapneumovirus or the bocavirus. Thus, their inclusion would not add to our discussion. Consult up-to-date journal articles for specific pathogens of interest. ,
Respiratory syncytial virus
RSV is the most common cause of bronchiolitis and pneumonia in the United States in children between the ages of 6 months and 3 years. The disease produced by RSV varies from upper respiratory tract infection to severe bronchiolitis and pneumonia with wheezing and respiratory failure. Higher mortality rates and greater severity with prolonged symptoms occur in infants and children younger than 6 weeks of age and in those who have a history of prematurity, chronic lung disease, cardiopulmonary disease, congenital heart disease, pulmonary hypertension, or neuromuscular impairment, as well as in those receiving chemotherapy or immunosuppressive therapy. , Signs of RSV pneumonia include wheezing, dyspnea, pulmonary infiltrates, and areas of atelectasis and hyperinflation on the chest radiograph. RSV infection may result in increased airway reactivity and airway resistance that persists for months. Significant respiratory tract shedding of virus continues for up to 21 days from the onset of illness. Nosocomial spread of RSV infection is common; early diagnosis and appropriate isolation techniques are critical in hospitalized patients.
Methods for diagnosis of RSV include viral isolation in cell culture, immunofluorescence of exfoliated nasopharyngeal epithelial cells for detection of RSV antigens, and enzyme immunoassay for detection of RSV antigens in nasal secretions. , PCR technology is also commonly used.
All hospitalized patients with bronchiolitis and RSV pneumonia should be monitored for hypoxia, hypercarbia, and the need for ventilatory assistance. Supportive care includes the use of humidified oxygen, secretion clearance, and hydration. , Mechanical ventilation for respiratory failure is usually well tolerated. Extracorporeal membrane oxygenation has been used successfully in infants who do not respond to conventional ventilation. , The routine administration of bronchodilators and corticosteroids is not warranted; use should be individualized on the basis of clinical response. , Passive immunoprophylaxis has proved useful in high-risk populations in preventing RSV infection, as has palivizumab, a humanized mouse monoclonal antibody. , The incidence of bacterial superinfection in persons with RSV disease is low; therefore, prophylactic antibiotics are not recommended for RSV disease. , , It is not unusual for an infant with RSV to require hospitalization for 7 to 10 days following the onset of illness. Long-term complications of RSV infection may include persistent bronchial reactivity, with lower respiratory tract symptoms in more than 70% of infants in the year following hospitalization. Whether moderately severe RSV infection predisposes a person to asthma later in life remains controversial.
Parainfluenza virus (types 1 and 2) is more often associated with laryngotracheobronchitis and croup than with pneumonia (usually type 3). Parainfluenza is second only to RSV as an etiology of lower respiratory tract disease responsible for the hospitalization of children. The pneumonia associated with parainfluenza is typically mild; however, fatal cases with prolonged viral shedding have been reported in patients with severe combined immunodeficiency disease. Conferred immunity following infection is low; repeat infection occurs in nearly 50% of patients by age 30 months, although it results in progressively milder illness. Parainfluenza virus, like RSV, has demonstrated the ability to elicit an immunoglobulin E–specific antibody response. Rapid identification of parainfluenza virus by either fluorescent or enzyme-linked immunologic techniques is possible, but results are variable depending on the viral type and antisera used. A viral culture may take up to 1 week. PCR methods are available for detection and differentiation, with high sensitivity and specificity. Treatment is supportive.
Adenoviruses are responsible for approximately 3% of the pneumonias occurring in children. Clinical features are similar to other viral pneumonias except that the onset of illness is often gradual, occurring over several days. Of the 51 serotypes, types 3, 4, and 7 are the most common causes of lower respiratory tract disease in children. Adenovirus type 7 is most commonly associated with severe pneumonitis in infants and children and has a significant incidence of mortality and morbidity. , In 2007, a new strain of adenovirus 14 was isolated in previously healthy infants and young adults in the United States in whom fatal pneumonia developed. A clinical presentation similar to that of bacterial pneumonia—with massive pleural effusion, rhabdomyolysis, and myoglobinuria—has been reported with adenovirus type 21. In many infants with documented adenovirus respiratory tract infection, chronic pulmonary disease develops, which manifests as persistent atelectasis, bronchiectasis, and recurrent pneumonitis with areas of hyperinflation and interstitial fibrosis. Bronchiectasis and restrictive lung disease have been documented in children following acute adenovirus infection. Adenovirus pneumonia is the most common cause of bronchiolitis obliterans in children, and unilateral hyperlucent lung syndrome has been reported. Disseminated adenovirus occurs and is usually associated with infection by serotype 3, 7, or 21. It occurs most frequently in infants younger than 18 months and usually involves the heart, pericardium, liver, pancreas, kidneys, CNS, and skin. Fatal cases of adenovirus and pneumonia can occur in previously healthy young individuals. Diagnosis is made by cell culture and antigen and DNA detection by PCR. Adenovirus typing is available from some reference and research laboratories. Treatment is mainly supportive in immunocompetent patients, but cidofovir and intravenous immunoglobulins (IVIGs) have been used in some immunocompromised patients.
Three antigenically distinct influenza viruses exist—types A, B, and C. All three have hemagglutinin surface antigen, but only types A and B have neuraminidase surface antigen. Antigenic drift for types A and B produces minor changes in the surface antigens, resulting in endemic illness. Antigenic shift occurs only with influenza type A, resulting in a major change or new surface antigen for which there may be low or no immunity in the population. Influenza type A is subtyped by its surface antigens; currently, three influenza strains are circulating worldwide, including influenza A/H1N1, H1N2, and H3N2. ,
Clinical signs of uncomplicated influenza pneumonia include coryzal symptoms followed by dyspnea, fever, cyanosis, cough, and wheezing. Children with influenza typically have a more sudden onset of “toxic” signs than do those with other viral diseases. Infection is associated with myalgia, encephalopathy, and cardiac involvement. Pathologically, influenza virus infection is similar to RSV in that the virus destroys ciliated respiratory epithelial cells with subsequent edema and an acute inflammatory response. Influenza has been associated with Reye syndrome and significant bacterial suprainfections. In patients in whom bacterial infection develops, there often is a period of apparent improvement before a sudden worsening that is heralded by the production of purulent sputum, return of fever, and development of pulmonary consolidation. Fatal outcomes have been reported in previously healthy children as well as in high-risk groups.
Prevention of influenza disease is possible with either administration of multivalent influenza vaccine (influenza A/H1N1, A/H3N2, and B) or chemoprophylaxis with oseltamivir or inhaled zanamivir (influenza A, B, and A/H1N1). One study showed the efficacy of aerosolized ribavirin in the treatment of persons with influenza B. , Diagnosis of influenza pneumonia may be made by a culture of the virus from respiratory secretions or with serologic techniques. Rapid diagnosis by means of immunofluorescence of exfoliated nasopharyngeal cells may be helpful, as well as by PCR. Treatment includes supportive care, monitoring of respiratory status, and administration of antiviral medications.
Measles is a highly contagious disease that is preventable by vaccine; the incidence fell below the endemic threshold in the United States in 2000. Endemic outbreaks continue in developing countries and when international travelers import measles to nonimmunized persons in the United States. , Typical disease manifests as high fever, cough, runny nose, and generalized rash. Respiratory symptoms are nearly universal in this illness, making the prevalence of measles pneumonia difficult to determine. Moist crackles develop in most children, and approximately 20% have expiratory wheezes and hypoxia. In cases in which radiographs have been obtained, a fine reticular infiltrate was present, compared with the nodular infiltrates in children with atypical measles. Although the clinical syndrome usually resolves over 1 to 2 weeks, both radiographic and pulmonary function abnormalities may persist for months. Severe life-threatening tracheitis may occur during the course of measles or bacterial suprainfection. In fatal cases, severe respiratory and nervous system diseases are manifested, and lung tissue demonstrating interstitial pneumonitis with diffuse endothelial cells, pneumatocyte degeneration, and presence of multinucleated giant cells has been reported.
Diagnosis is made by isolation of the virus, standard serology, or identification of viral ribonucleic acid by reverse transcription PCR. All suspected cases should be reported to local and state health departments. No antiviral agent is available; treatment is supportive. Two doses of vitamin A (200,000 International Units on consecutive days) have been shown to reduce pulmonary-specific and overall mortality rates in patients up to 2 years of age. Administration of IVIG may be of benefit to high-risk or immunosuppressed patients when it is started within 6 days of exposure.
Human immunodeficiency virus
Human immunodeficiency virus (HIV) infection in children most commonly presents with recurrent bacterial infections. The major causes of morbidity and mortality in pediatric AIDS patients are associated with lung disease, ranging from opportunistic infections such as Pneumocystis jiroveci pneumonia to entities such as chronic interstitial pneumonitis. , Treatment for specific pulmonary pathogens is discussed throughout this chapter, but specific guidelines for HIV/AIDS treatment are lengthy, rapidly changing, and beyond the scope of this chapter.
The actual mechanisms by which viruses predispose the lung to secondary bacterial infection are not precisely understood. Viruses are capable of altering both cellular and noncellular defenses of the respiratory tract. , , Viral infection of the epithelial cells appears to predispose the upper respiratory tract mucosa to bacterial colonization by allowing bacterial pathogens to adhere to injured cells. , Viral infection may cause significant impairment of both intracellular killing and ingestion of bacteria by the pulmonary macrophage. Significant defects in polymorphonuclear leukocyte chemotaxis and phagolysosome fusion occur during acute viral infection. The greatest impairment of macrophage function occurs 1 week after the onset of viral infection, which correlates with the peak incidence of bacterial superinfection. Thus, superinfection during the course of viral lower respiratory tract disease appears to be the result of a combination of the cytopathic effects of the virus on the respiratory mucosa and various alterations in host immune response.
Significant life-threatening complications of viral lower respiratory tract disease are noted in Table 52.5 . Respiratory failure with viral pneumonitis resembling ARDS is frequently seen in patients in the pediatric critical care unit. It is often associated with influenza or adenovirus but can occur with varicella, cytomegalovirus, and RSV.
|Subacute sclerosing panencephalitis||Measles|
|Guillain-Barré syndrome||Influenza, varicella|
|Reye syndrome||Influenza, VZV|
|Encephalitis||Adenovirus, measles, RSV, CMV|
|Bacterial superinfection||Influenza, VZV, Epstein-Barr virus, measles|
|Asthma||RSV, parainfluenza, rhinovirus|
|Bronchiolitis obliterans||Influenza, adenovirus, measles|
|Chronic obstructive pulmonary disease||RSV|
|Fatal pneumonitis||Influenza, measles, adenovirus, RSV, parainfluenza, CMV|
|Tracheitis, life-threatening||Measles, parainfluenza|
|Hepatitis||Adenovirus, influenza, measles, CMV|
|Nephritis||Adenovirus, influenza, measles|
|Myocarditis||Adenovirus, influenza, measles|
|Pericarditis||Adenovirus, influenza, measles|
Several techniques are available for establishing a viral diagnosis. In the critical care setting, the decision to undertake these diagnostic measures should be guided by how awareness of the specific viral illness will affect clinical management. Potential benefits include (1) a guide to the selection of appropriate antiviral therapy and avoidance of unnecessary treatments with antibiotics and (2) initiation of appropriate infection control measures and the use of a vaccine or drug prophylaxis. Direct isolation of viruses is a sensitive method of diagnosis early in the course of a disease when a large number of infectious particles are present in respiratory secretions. Nasopharyngeal washings are the preferred specimens for viral cultures because large quantities of secretions for culture are easily available. Unfortunately, viral isolation may require up to 2 weeks for positive culture results. Serologic testing or diagnosis depends on the demonstration of a rising antibody titer between acute and convalescent sera. Although serologic data may provide a diagnosis, they are of little value in guiding therapeutic critical care interventions. The more commonly used methods for viral diagnosis involve the detection of viral antigens present in respiratory secretions. These antigen-detection techniques using radioimmune or enzyme-linked assays can detect all riboviruses and adenoviruses that commonly produce lower respiratory tract infections. Antibody detection has also been used successfully in the diagnosis of lower respiratory tract viral disease (cytomegalovirus pneumonia). A major advantage of tests capable of detecting viral components is that these studies can be performed rapidly and the results made available to the critical care physician in hours, allowing timely management.
Prevention and treatment
Guidelines for influenza chemoprophylaxis and treatment are lengthy and rapidly changing. Specific and current information regarding the use of antiviral drugs is available at www.aapredbook.org/flu or www.cdc.gov/flu/professionals/antivirals/index.htm .
Passive immunization is also available for some viruses that can be associated with pneumonitis, but recommendations are ever-changing. Check the Centers for Disease Control and Prevention (CDC) recommendations and see Table 52.3 .
Amantadine, rimantadine, oseltamivir, and zanamivir are approved for prophylaxis of viral respiratory tract infection caused by influenza. Amantadine and rimantadine have been shown to be effective prophylaxis for influenza type A. However, they are not active against influenza type A/H1N1 or influenza type B. Therefore, they are no longer recommended for prophylaxis. Oseltamivir and zanamivir have activity against influenza types A, B, and A/H1N1. Oseltamivir resistance has been reported among persons with influenza type A/H1N1 strains globally, but no significant resistance has been reported among persons with influenza type A/H1N1 strains circulating in the United States. Oseltamivir and zanamivir are recommended for persons at high risk for serious influenza infection who have not been vaccinated or who have received the vaccine within 2 weeks of the onset of an epidemic. They are also recommended for persons in whom appropriate immune response may not develop following vaccination and for persons who cannot receive the influenza vaccine because of allergic reactions. , ,
Several antiviral agents inhibit the replication of respiratory viruses in vitro. Some of these drugs have been used clinically in both experimental and naturally occurring respiratory infections ( Table 52.6 ). Most influenza A and B virus strains are susceptible to oseltamivir and zanamivir. , These neuraminidase inhibitors have been shown to reduce the severity and duration of illness. Resistance to oseltamivir has been reported in persons with influenza type A/H1N1 strains but not A/H3N2 or B strains. Zanamivir is effective against influenza types A, B, and A/H1N1, but it has not been approved for therapeutic use in children younger than 7 years. Peramivir was approved to treat influenza infection in adults in December 2014. Peramivir is the first neuraminidase inhibitor approved in IV form. Peramivir is a neuraminidase inhibitor and should not be administered if the patient has a severe allergy to oseltamivir, zanamivir, or one of their metabolite components. Oral baloxavir is effective against influenza types A and B but has a different mechanism of action than neuraminidase inhibitors. Resistance patterns are perpetually changing; for the most up-to-date information regarding resistance patterns, see the CDC website at www.cdc.gov/flu/professionals/antivirals/ .
|Acyclovir||HSV, varicella |
|IV, PO||Phlebitis, seizures, leukopenia, renal dysfunction|
|Valacyclovir||HSV, varicella |
|PO||Bone marrow suppression, renal failure|
|Ganciclovir||CMV in immunocompromised host |
|IV, PO||Renal failure, bone marrow suppression, seizure|
|Valganciclovir||CMV prophylaxis||PO||Same as ganciclovir|
|Baloxavir||Influenza types A and B |
|PO||None more common than placebo in clinical trials|
|Zanamivir||Influenza types A and B |
Treatment, prophylaxis under study
|Oseltamivir||Influenza types A and B |
|PO||Nausea, vomiting, vertigo|
|Peramivir||Influenza type A and limited type B treatment||IV||Stevens-Johnson syndrome, erythema multiforme, neuropsychological events, and diarrhea|
|RSV-IVIG||RSV prophylaxis (high-risk population)||IV||Allergic, fluid overload, not approved for CCHD|
|Ribavirin||RSV (parainfluenza, influenza types A and B, measles)||Small-particle aerosol||Conjunctival edema|
|Foscarnet||CMV retinitis, HSV resistant to acyclovir||IV||Renal dysfunction, nausea, bone marrow suppression|
|Pleconaril (under investigation)||Enterovirus and rhinovirus |
Ribavirin is a synthetic nucleoside analog licensed for use in aerosol form for the treatment of persons with severe RSV infection. This therapy may shorten the course of the illness and improve oxygenation in high-risk patients. A few children with severe combined immune deficiency have been treated with ribavirin with resulting clinical improvement and decrease in viral shedding. , Ribavirin aerosol may be effective in shortening the course of both influenza types A and B in infections in college students, and it is possible that parainfluenza and the measles virus can be treated with ribavirin. Various case reports of treatment in seriously ill adults with complicated viral infections suggest that ribavirin may be an effective treatment. Overall, the documented therapeutic benefit of antiviral agents has been inconclusive. Improvement is most apparent when the therapy was initiated early after the onset of infection. Future investigations are necessary to define the optimum dose/route of antiviral agents for each respiratory virus/pneumonia and to clarify the ability of antiviral therapy to modify serious lower respiratory tract infection in high-risk infants and children.
In persons with varicella or zoster, acyclovir reduces the period of viral shedding and the time needed to heal skin lesions. It can also prevent the dissemination of localized zoster in immunocompromised children. Thus, the use of acyclovir in immunosuppressed patients can be justified by the low toxicity of the drug and the potential severity of the illness. Ganciclovir is an antiviral drug with significant activity against cytomegalovirus. It has been used successfully in immunocompromised patients with disseminated cytomegalovirus and pneumonia. Symptomatic infection of the lower airway with herpes viruses is rare. When it occurs, it usually does so in an immunosuppressed child. Antiviral therapy for herpes viruses includes acyclovir, foscarnet, and adenine arabinoside. ,
Fungal infections are becoming increasingly important in the differential diagnosis of pulmonary infections, particularly in immunocompromised hosts. The majority of pulmonary mycotic infections occur in two microbiologic and clinical groups ( Box 52.2 ). In general, different patient groups are at risk for infection because of either opportunistic or pathogenic dimorphic pulmonary fungi. Primary pulmonary mycotic infections generally infect healthy children exposed to the pathogen in a particular geographic or environmental setting, whereas the opportunistic mycoses occur in children whose immunity is compromised. , The increase in opportunistic fungal infections can be attributed to numerous factors, including the following:
Selection of fungal organisms as flora by the use of broad-spectrum antibiotics
Leukopenia secondary to use of cytotoxic agents
Suppression of humoral and cell-mediated immunity by cytotoxic and suppressive therapy
Increased use of immunosuppressive drugs in patients with an organ transplant or collagen vascular disease
An increasing number of patients with AIDS
An increased number of invasive surgical procedures in hospitalized children, which create portals of entry for fungi
Primary pulmonary fungi
Fungi that cause primary pulmonary infection in otherwise healthy hosts are generally endemic mycoses found in a particular geographic distribution. The four major mycoses in this group are histoplasmosis, blastomycosis, coccidiomycosis, and paracoccidiomycosis. Chemiluminescent DNA probes are available for identification of blastomycosis, coccidioidomycosis, and histoplasmosis. We review these primary pulmonary mycoses in the following section but exclude paracoccidiomycosis because this infection occurs primarily in South America, Central America, and Mexico. Consult up-to-date journal articles for information regarding paracoccidiomycosis infections.
The dimorphic fungi cause infection following inhalation of spores (conidia) into the pulmonary system. In the lower respiratory tract the conidia transform into the yeast phase, which is susceptible to phagocytosis by the pulmonary macrophages. These yeast forms may persist in the nonimmune host. As the yeast-laden macrophages are transported via the lymphatics to the peribronchial and mediastinal lymph nodes, hematogenous dissemination may occur. However, with the primary pulmonary infection in the immunocompetent host, extrapulmonary infection is rare.
Progressive primary pulmonary infection in the absence of host defenses (such as in a patient who is immunocompromised or an infant) may lead to seeding of extrapulmonary sites, dissemination, and death if left untreated. Cellular immunity is the primary host defense against these deep mycoses, many of which are subclinical and require no therapy. However, children with severe life-threatening infections should be treated ( Table 52.7 ).