Abinash Virk MD
Walter R. Wilson MD
ACUTE BRONCHITIS
Essentials of Diagnosis
General Considerations
Acute bronchitis is a common inflammatory condition of the tracheobronchial tree that results in many physician visits worldwide. By definition the inflammation is limited to the trachea and large and medium-sized bronchi, with absence of infection of the alveoli or lower respiratory tract.
Community-acquired respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus, coronavirus, adenovirus, influenza viruses, and parainfluenza viruses, are the most common causes of acute bronchitis (Box 10-1). Occasionally, herpes viruses and, more rarely, measles virus cause acute bronchitis. Less often, nonviral etiologies are implicated, such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and, more rarely, Bordetella pertussis. Sputum cultures from patients with acute bronchitis may be positive for Streptococcus pneumoniae or Haemophilus influenzae; however, the role of these organisms in pathogenesis is unclear and may represent oral or upper respiratory tract colonization with no etiologic role. A small proportion of acute-bronchitis cases may be caused by noninfectious injury to the bronchial epithelium, eg, by exposure to pollution or other toxic substances.
Infection of the tracheobronchial epithelium results in various degrees of epithelial injury (depending on the infecting organism), which in turn results in a local acute polymorphonuclear (PMN) inflammatory response, edema, and hyperemia of the mucous lining. The mucous and serous glands of the bronchial lining secrete abundant mucus during this inflammation. Normally, ciliated epithelium of the bronchi aid in the upward passage of mucus, thereby preventing infection of the bronchioles and alveoli. This protective mechanism may not occur in infants or patients with other comorbid conditions such as chronic obstructive pulmonary disease. Smoking or exposure to air pollutants can increase the severity of attack.
Clinical Findings
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BOX 10-1 Microbiology of Acute Bronchitis |
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Differential Diagnosis
Cough is a common symptom of a number of cardiopulmonary diseases. Diagnosis of acute bronchitis should be made after appropriate evaluation and exclusion of other causes of cough. New onset of cough caused by pneumonia, presence of a foreign body, toxic-fume injury, drug side effects such as angiotensin-converting enzyme inhibitors, endobronchial malignancy, or congestive heart failure may be mistaken initially for acute bronchitis. Tuberculosis should be excluded in cases with chronic cough, particularly in patients with high-risk profiles, including immigrants, intravenous drug abusers, homeless populations, and those with previous tuberculosis exposure or immunocompromised status.
Complications
Most episodes of acute bronchitis resolve spontaneously. However, patients with underlying chronic cardiopulmonary diseases, such as chronic obstructive lung disease (COPD), congestive heart failure, or severe immunosuppression, may develop respiratory compromise that requires hospitalization and, in severe cases, mechanical ventilation. Cough in otherwise healthy persons may persist for 6–8 weeks because of increased airway reactivity.
Treatment
Because acute bronchitis is most often a viral infection, the majority of the episodes of community-acquired acute bronchitis require only symptomatic therapy and do not need antibiotic therapy. Nonetheless, studies have shown that 66% of patients with acute bronchitis are prescribed antibiotics for this self-limited disease. Antibiotic therapy for acute bronchitis should be reserved only for select patients, including the elderly, those with underlying cardiopulmonary disease and persistent cough (lasting >7–10 days), or immunocompromised patients. The choice of antibiotics in such patients should be directed against S pneumoniae, H influenzae, Mycoplasma spp., or C pneumoniae. Antibiotics that can be administered on an outpatient basis and adequately cover these organisms include newer-generation macrolides such as clarithromycin, azithromycin, and doxycycline or a fluoroquinolone such as levofloxacin, administered for a 7- to 10-day course (Box 10-2). Hospitalized patients with acute bronchitis warrant antimicrobial therapy more often than do ambulatory patients. The choice of empiric antimicrobial therapy is the same for outpatients and inpatients.
Symptomatic therapy includes cough suppressants, adequate hydration, and antipyretics as necessary. Occasionally, patients may require β-adrenergic bronchodilators such as albuterol inhalers for bronchospasm associated with acute bronchitis.
Prognosis
Prognosis for patients with acute bronchitis is excellent. Morbidity and mortality are higher among patients with an underlying comorbid condition.
Prevention
Hand washing is an important measure in preventing the acquisition of viruses that cause viral lower respiratory tract infections (LRTIs) (Box 10-3). Care must also be taken in handling fomites from a person who is ill. Annual administration of influenza A/B vaccine is important for the prevention of influenza virus infection. Amantadine or rimantadine should be administered to exposed nonimmunized individuals. Active immunization with 23 polyvalent pneumococcal vaccine should be administered to high-risk patients. Droplet isolation for hospitalized patients, especially for infants and children, with Mycoplasma, influenza, RSV, and parainfluenza infections is recommended.
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BOX 10-2 Empiric Therapy of Acute Bronchitis1 |
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BOX 10-3 Control of Acute Bronchitis |
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CHRONIC BRONCHITIS & ACUTE EXACERBATIONS
Essentials of Diagnosis
General Considerations
Chronic bronchitis is defined as chronic productive cough present for ≥3 months during 2 consecutive years. Chronic bronchitis and acute exacerbations are clinical syndromes associated with COPD. COPD is characterized by obstruction to airflow in the distal airways. Pulmonary-function tests, especially forced expiratory volume at 1 s, are used to assess the severity and prognosis of the disease.
The essential pathological change in chronic bronchitis is the alteration of the epithelial lining of the bronchi. Initially, because of cigarette smoking, dust, or other chemical irritants, attacks of acute bronchitis occur. The initial airway changes include acute inflammatory PMN cell infiltration, hyperemia, edema, and increases in mucous and serous gland secretion that lead to mucus production. Over time and with repeated attacks of bronchitis, loss of the serous glands and hypertrophy of mucous secreting glands occur. The increase in tenacious secretions and ongoing destruction of the ciliated epithelium of the bronchi lead to inability to clear the bronchial lumen and further retention of mucus. The retained secretions encourage bacterial growth, which may result in repeated attacks of infection and inflammation.
The role of bacterial infection in chronic bronchitis and exacerbation is unclear. Bacteria do not seem to cause the initial bronchitis; however, they may play a role in acute exacerbations (Box 10-4). Randomized, placebo-controlled studies evaluating the role of antibiotic therapy and of bacteria in acute exacerbations show improved outcomes with antibiotic therapy, which suggests a causal relationship of the bacteria with AECB. Pathogenic bacteria may be recovered from normally sterile bronchi in the majority of patients with chronic bronchitis or during exacerbations. Chronic pathologic changes in the bronchi occur as cycles of recurrent bronchitis continue and are worsened by persistent exposure to noxious agents such as cigarette smoking or air pollutants. Ciliated epithelium disappears; goblet cells, which are normally not present, appear, resulting in partial obstruction of bronchi and atelectasis or consolidation distal to the obstructed lumen. Pathologically, severity of disease is measured by the Reid index, which is the ratio of the submucous layer (layer containing the mucous glands) to the thickness of the bronchial wall. The normal Reid index is 0.3; in chronic bronchitis the index is higher. In the later stages of the disease, the bronchial wall may become atrophic and thin.
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BOX 10-4 Microbiology of Acute Exacerbation of Chronic Bronchitis |
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Sputum may be chronically colonized with Haemophilus spp., S pneumoniae, or M catarrhalis in more than half of these patients. Bacteria such as Staphylococcus aureus or gram-negative bacilli occur less frequently. AECB may be precipitated by a viral infection. Viruses account for 25–50% of the acute exacerbations. These are usually the seasonal community-acquired viruses, such as influenza, parainfluenza, adenovirus, or RSV. Other microorganisms such as M pneumoniae or C pneumoniae are infrequent causes of infection.
Clinical Findings
Patients have accompanying symptoms and signs of COPD. In some patients, chronic bronchitis predominates, whereas others have symptoms of emphysema alone or a combination of both. Patients with chronic bronchitis develop severe functional, bronchitis-mediated structural damage to bronchioles and alveoli and have minimal compensatory mechanisms or increase in lung capacity. Spasm and stenosis of the bronchioles lead to difficulty in inspiration, hyperinflation, reduced inspiratory flow, and reduced oxygen tension in the alveoli. Patients with these changes that result in chronic reduced oxygenation, cyanosis, and severe dyspnea are referred to as the “blue bloaters.” Patients complain of dyspnea, lethargy, and somnolence. Daily cough is accompanied by copious amounts of sputum. On physical examination, clubbing of the extremities and cyanosis are common. Rhonchi, coarse crepitations, and wheezing may be heard on chest auscultation. Eventually, chronic hypoxemia and respiratory acidosis lead to increased pulmonary vascular resistance and pulmonary artery hypertension, which may result in right-heart failure or cor pulmonale. On physical examination, cor pulmonale results in peripheral edema, jugular venous engorgement, and hepatomegaly.
Patients with primarily emphysema, as opposed to those with primarily bronchitis, lose alveolar elasticity, which results in increased lung capacity, slowing of alveolar gas movement, and diminished oxygen exchange. Compensatory mechanisms lead to an increase in the respiratory rate to maintain normal oxygen and carbon dioxide exchange. As a result, these patients are described as “pink puffers,” who are dyspneic but not cyanotic. Eventually, with progressive destruction of the alveoli, this compensatory mechanism fails. These patients are characteristically thin and barrel-chested, and they have hypertrophied accessory respiratory muscles. Expiration is prolonged and may be through pursed lips. Percussion of the chest is hyperresonant. Auscultation reveals diminished breath sounds, prolonged expiration, and often wheezing. Cor pulmonale is relatively uncommon in these patients but occurs in terminal stages.
Differential Diagnosis
Congestive heart failure or acute myocardial infarction can be mistaken for AECB. An electrocardiogram, cardiac enzymes, and echocardiography can help to exclude cardiac causes of symptoms. Pulmonary malignancy should be considered in smokers. Other conditions that may present in a manner similar to chronic bronchitis are chronic aspiration or recurrent asthma attacks. In younger patients, cystic fibrosis, epithelial ciliary defect, immunoglobulin deficiency (IgA or subclasses of IgG), or defects in neutrophil function should be considered in the differential diagnosis.
Complications
Repeated attacks of chronic bronchitis can lead to right-heart failure or cor pulmonale. In acute cases, patients with minimal pulmonary reserve may develop respiratory failure that requires mechanical ventilation. Mechanical ventilation is required for 20–60% of hospitalized patients with AECB.
Treatment
Management of chronic bronchitis can be divided into two broad categories—symptomatic and antimicrobial therapy.
Airway management includes clearance of secretions and use of bronchodilators. Secretions may be tenacious and difficult to clear. A good cough is the best mechanism for clearing secretions. Mobilization of secretions can be increased by the use of bronchodilators followed by chest physiotherapy and postural drainage. Mucolytics and cough suppressants are not recommended. Mucolytics can be irritants and can increase sputum production.
Inhaled-bronchodilator therapy with β-adrenergic or anticholinergic agents, either alone or in combination, is useful in patients with chronic bronchitis, particularly during acute exacerbations. Aerosol nebulization can be used to administer bronchodilators such as albuterol and ipratropium bromide. Patients with acute exacerbations may require supplemental oxygen. However, excessive oxygen may cause hypercarbia by overriding the hypoxic ventilatory drive. Therefore, if oxygen is used, levels of partial arterial O2 (PaO2) and partial arterial CO2 (PaCO2) should be carefully monitored.
Parenteral corticosteroids have been shown to improve pulmonary-function tests more rapidly than placebos among patients with acute exacerbations.
Patients with progressive disease and repeated hospitalizations are more prone to colonization with nosocomial gram-negative bacilli instead of or in addition to the usual oropharyngeal bacteria. It is prudent to choose empiric antibiotics to cover these organisms in such circumstances. Use of a fluoroquinolone such as levofloxacin or gatifloxacin is appropriate until sputum culture and susceptibility data can help guide further modification.
Administration of prophylactic antibiotics in patients with chronic bronchitis is usually not recommended unless a high-risk patient has >4 exacerbations/year. Options include monthly rotation of antibiotics, daily antibiotic therapy during winter, or antibiotics started as soon as there is a change in pulmonary symptoms or onset of an upper respiratory infection. The use of prophylactic antibiotics should be individualized for each patient, based on factors such as the development of antimicrobial resistance, cost, and side effects. Patients on chronic antibiotic therapy are likely to become colonized with resistant bacteria that reduce therapeutic options for subsequent oral antibiotic therapy.
Prognosis
Advanced age (>65 years), presence of other underlying diseases such as cardiac disease, multiple previous episodes of AECB, especially those requiring steroids, and severity of underlying COPD are poor prognostic factors. The mortality of hospitalized patients with AECB is ~10–30%.
Prevention
Smoking cessation is the most important factor in prevention of AECB (Box 10-6). Patients should be immunized with influenza vaccine and the 23 polyvalent pneumococcal vaccine.
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BOX 10-5 Empiric Therapy of Acute Exacerbation of Chronic Bronchitis1 |
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BOX 10-6 Control of Acute Exacerbation of Chronic Bronchitis |
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BRONCHIOLITIS
Essentials of Diagnosis
General Considerations
Bronchiolitis is defined as inflammation of the bronchioles as a response to injury because of infections, vasculitis, chemical exposure such as that from cigarette smoking, or transplant-associated airway injury. Infectious bronchiolitis is mainly a disease of infants and young children. Of infants < 1 year of age, ~1–6% will develop viral bronchiolitis. Viruses are the most common infectious causes of bronchiolitis (Box 10-7). These include RSV, parainfluenza virus types 1 and 3, influenza virus types A and B, adenovirus, rhinovirus, and enteroviruses. RSV is the most common cause, accounting for 45–75% of all bronchiolitis among infants, followed by parainfluenza virus. RSV is the most common cause of nosocomial bronchiolitis. Bronchiolitis has seasonal distribution with highest incidence in the winter, when RSV activity increases. Parainfluenza infections occur during the fall and spring. Risk factors for severe bronchiolitis and possible hospitalization include male sex (male:female = 1.5:1), prematurity, overcrowding, comorbidities such as congenital heart disease or chronic lung disease such as bronchopulmonary dysplasia, and lack of breast-feeding.
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BOX 10-7 Microbiology of Acute Bronchiolitis |
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Acute bronchiolar inflammation occurs. Peribronchial mononuclear inflammation and resultant edema of the submucosa and adventitia may develop, resulting in bronchiolar epithelial necrosis. These changes may result in partial or complete bronchiolar obstruction and distal atelectasis, especially in infants. Positive pressure during expiration increases the degree of obstruction in the bronchioles. Inflammation and bronchospasm may be the result of virus-specific IgE, leukotriene C4, or other inflammatory mediators.
Clinical Findings
Differential Diagnosis
The differential diagnosis of bronchiolitis includes asthma or aspiration. The diagnosis is more likely to be bronchiolitis if wheezing occurs at < 1 year of age, RSV is detected, and there is no prior history of wheezing or family history of atopy. Other conditions that may simulate bronchiolitis include cystic fibrosis, lymphoid interstitial pneumonia as seen in HIV/AIDS patients, and congestive heart failure in very young infants.
Complications
Immediate complications include apneic spells, dehydration, hypoxia, and respiratory failure. Apnea occurs more frequently among premature or very young infants. Dehydration results from diarrhea, anorexia, or repeated coughing spells that cause vomiting. Mucus plugging, atelectasis, pneumonia, and ventilation-perfusion mismatch may cause respiratory failure. Immunocompromised children or those with comorbidities such as chronic pulmonary or cardiac disease or prematurity are more likely to develop a severe infection that requires ventilatory support.
Late complications include an increased tendency to develop recurrent hyperactive airways. This may occur in as many as two-thirds of the patients and persist ≤2–7 years after the episode, but this tendency gradually resolves. The risk of this late complication is less in children with mild disease that does not require hospitalization.
Treatment
Therapy of bronchiolitis is based on the severity of disease (Box 10-8). In mild cases, outpatient management can be initiated with adequate hydration, feeding, and close follow-up. Children should be hospitalized if there is a history of underlying disease or prematurity; they are < 3 months of age; or they have pulse oximetry of < 93% on room air, apnea, severe dehydration, or signs of severe respiratory distress.
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Figure 10-1. Respiratory syncytial virus (RSV) bronchiolitis and pneumonitis. A. Chest radiograph shows patchy perihilar infiltrates, overinflated lungs, and atelactasis in the right upper lobe. The radiograph depicts the airway distribution of the RSV infection. Consolidation, pleural effusion, and hilar adenopathy are rare. B. Follow-up chest radiograph taken 3 months later shows complete resolution of the infiltrates. |
The cornerstone of inpatient management of bronchiolitis is the judicious use of oxygen and supportive care, including hydration and feeding. Oxygen saturation should be maintained above 95%. Some high-risk infants will require mechanical ventilation.
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BOX 10-8 Empiric Therapy of Acute Bronchiolitis1 |
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The use of bronchodilators in bronchiolitis is controversial. Some studies show a benefit; others do not. Numerous studies have shown no benefit from corticosteroid therapy.
There is considerable debate regarding the use of aerosolized ribavirin for patients with RSV bronchiolitis. Ribavirin inhibits viral protein synthesis and is active in vitro against RSV. Initial studies that compared ribavirin with a placebo indicated significant improvement in oxygenation and decreased length of hospitalization in patients treated with aerosolized ribavirin. However, recent studies comparing ribavirin with a placebo did not show the same benefits for ribavirin therapy and, in fact, indicated that ribavirin therapy may prolong hospitalization. Accordingly, because of lack of clear benefit, high cost, and difficult delivery systems, the American Academy of Pediatrics recommends use of ribavirin only for a select population and at the discretion of the physician caring for the child with RSV bronchiolitis. Aerosolized ribavirin may be considered for high-risk patients such as those with a chronic underlying disease (pulmonary or cardiac), those in a severe immunocompromised state (organ transplant patients or patients with AIDS), those with severe RSV disease either with or without the need for mechanical ventilation, and those born prematurely at < 37 weeks gestational age or for infants < 6 weeks old.
Prognosis
Overall, the prognosis of patients with bronchiolitis is good. The prognosis is worse in an immunocompromised host or in children with chronic cardiopulmonary diseases. Mortality among hospitalized infants with RSV bronchiolitis ranges from 0.5% to 1.5%.
Prevention
Children, especially those with high-risk factors, should avoid contact with individuals with respiratory infections (Box 10-9). The American Academy of Pediatrics recommends the use of RSV immunoglobulin prophylactic therapy (RSV-IGIV) for patients at high risk for severe RSV disease. These include premature infants (infants with a gestational age < 28 weeks or between 29 and 32 weeks may benefit from RSV-IGIV therapy until 12 months or 6 months of age, respectively), children with bronchopulmonary dysplasia who are < 24 months postnatal age and are currently using oxygen or have used oxygen within in the last 6 months, or severely immunocompromised children. RSV-IGIV has been shown to decrease RSV-related hospitalizations by 41–63%. RSV-IGIV is given monthly at the onset of the RSV season between October and April. RSV-IGIV is not approved or recommended for children with cyanotic heart disease because of possible higher mortality associated with RSV-IGIV prophylactic use in these patients. A new humanized RSV monoclonal antibody, palivizumab, is being studied as prophylaxis for high-risk patients. Palivizumab was effective in reducing the incidence of RSV hospitalization from 10.6% in the placebo group to 4.8% in the palivizumab group (a 55% decrease in RSV hospitalizations) and decreasing intensive-care unit admissions. The Food and Drug Administration has approved palivizumab for preventive use in patients at high risk of severe RSV infections.
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BOX 10-9 Control of Acute Bronchiolitis |
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Hospitalized patients with bronchiolitis should be placed in contact isolation to prevent nosocomial spread of the virus.
PNEUMONIA
Essentials of Diagnosis
General Considerations
Entry of a pathogen into the lower respiratory tract induces a host inflammatory response that results in a fibrino-cellular exudate and consolidation of alveoli and smaller airways. This process is referred to as pneumonia. Patients present with symptoms and signs of an acute infection with associated radiographic findings. Pneumonia may be classified by microbiologic etiology, community versus hospital or nursing home setting, severity of onset (acute or chronic), or histologic appearance.
Certain host factors predispose patients to LRTIs. These include extremes of age; underlying diseases such as congestive heart failure, chronic renal disease, diabetes mellitus, chronic obstructive pulmonary disease, malnutrition, alcoholism, malignancy, cystic fibrosis or tracheobronchial obstruction; and institutionalization. Cerebrovascular diseases, dementia, and seizure disorders are also associated with an increased risk for LRTI. Risk factors for pediatric pneumonia include attendance at a day-care center, low birth weight, low maternal age, absence of breast-feeding, or a previous history of pneumonia or wheezing.
Neonates are at an increased risk of CAP caused by gram-positive cocci, particularly group B streptococcal or staphylococcal pneumonia. There is also a predisposition to gram-negative bacillary pneumonia in this population. The risk for S aureus or gram-negative bacilli decreases with age. In children >1 month old, viruses such as RSV, adenovirus, and influenza viruses play an important role in LRTI. Bacterial causes of pneumonia in children include S pneumoniae, H influenzae, and, occasionally, group A streptococci. The latter may complicate primary varicella infection. M pneumoniae is an important etiology of CAP, especially in school-aged children.
Among adults, no pathogen is identified in 33–47% of patients with CAP. S pneumoniae (30%) is the most common bacterial cause of CAP. Elderly patients, HIV-infected patients, and immunosuppressed, asplenic patients with immunoglobulin deficiencies or chronic cardiovascular, pulmonary (COPD, chronic bronchitis), or renal diseases are particularly predisposed to pneumococcal pneumonia. CAPs by encapsulated organisms like S pneumoniae, H influenzae, and Neisseria meningitidis are more common among patients with sickle cell disease, AIDS, asplenia, and immunoglobulin deficiencies.
C pneumoniae is the second most common cause of CAP requiring hospitalization. H influenzae type B or nontypable H influenzae is a common cause of CAP. M pneumoniae, M catarrhalis, and L pneumophila are other bacterial etiologies of CAP. Occasionally, S aureus, Chlamydia psittaci, Coxiella burnetii (the agent of Q fever), anaerobes, or aerobic gram-negative bacilli are the etiologic agents for CAP. Legionnaires' disease is caused by various Legionella spp., L pneumophila being the most common. Legionella spp. probably account for 2–6% of all hospitalized cases of CAP. They are associated with exposure to contaminated air-conditioning cooling towers or other contaminated water sources. S aureus pneumonia usually results from bacteremic spread to the lung and is often associated with endocarditis.
S pneumoniae, H influenzae, or M catarrhalis often causes pneumonia among patients with chronic pulmonary disease (COPD, chronic bronchitis). Nursing home residents are predisposed to pneumonia caused by S pneumoniae, gram-negative bacilli, influenza virus, RSV, and S aureus. Patients with structural pulmonary disease (cystic fibrosis or bronchiectasis) are commonly colonized and infected with gram-negative bacilli such as P aeruginosa, Stenotrophomonas maltophilia, or Ralstonia (Burkholderia) cepacia (Box 10-11). Alcohol use is also associated with pneumonia and colonization with aerobic gram-negative organisms such as Klebsiella pneumoniae; however, S pneumoniae is the most common cause of CAP among alcoholics. Children and adults with recurrent sinopulmonary infections should be suspected of having specific congenital or acquired conditions, such as abnormal leukocyte function, mucociliary defect (Kartagener syndrome), or immunoglobulin deficiencies.
Influenza virus accounts for 7–8% of all CAP, whereas community viruses such as RSV, cytomegalovirus (CMV), adenovirus, and others such as hantavirus are seen in specific epidemiologic settings. RSV pneumonia is more common in young infants, particularly those with cardiopulmonary diseases, or in patients with severe immunosuppression, as in bone marrow transplantation. CMV pneumonia is most often associated with patients with bone marrow transplantation, solid organ transplantation, or, occasionally, AIDS. Seasonal variation such as the predilection of RSV and influenza viruses for winter may help differentiate the etiology. Influenza pneumonia has a higher incidence of secondary infection with S pneumoniae or S aureus.
HIV-infected patients have predisposition for pneu-monia caused by unusual pathogens such as Pneumocystis carinii, Rhodococcus equi, or fungi such as Histoplasma capsulatum or Cryptococcus neoformans. Mycobacterium tuberculosis causes CAP and should be considered among HIV-infected patients, homeless populations, intravenous drug abusers, immigrants, and institutionalized and nursing home patients.
Specific exposures provide clues to the microbiologic agent, such as Coccidioides immitis pneumonia in the southwest United States. Histoplasmosis is associated with exposure to bird droppings or bats. Psittacosis, caused by C psittaci, occurs after exposure to birds. Exposure to parturient cats or other animals is an epidemiological risk for C burnetii pneumonia. Hunting and skinning of rabbits, deer, or other wild animals are associated with F tularensis pneumonia. Recent or remote travel to Southeast Asia is associated with Pseudomonas pseudomallei pneumonia.
Aspiration pneumonia is predominantly caused by the oral flora, including aerobes and anaerobes such as Peptostreptococcus spp., Prevotella spp., and Bacteroides spp., that form a large percentage of the microorganisms found in the mouth. Aspiration pneumonia must be considered among patients with seizures, neurological disease that impairs swallowing, altered mentation, vomiting, gastroesophageal reflux disease, and periodontal disease.
Mechanical factors that impair cough and epiglottic reflexes predispose patients to aspiration. These include an impaired gag reflex that may be caused by neurologic disease, seizures, gastroesophageal reflux disease, anesthesia, or mental retardation.
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BOX 10-10 Microbiology of Community-Acquired Pneumonia |
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BOX 10-11 Microbiology of Infections in Patients with Cystic Fibrosis |
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BOX 10-12 Microbiology of Nosocomial Pneumonia |
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Clinical Findings
Lack of temperature elevation and confusion may occur in elderly patients. Patients with pneumococcal pneumonia typically develop sudden shaking, chills, fever, and mucopurulent, blood-tinged sputum, and they often have pleuritic chest pain. Gastrointestinal symptoms such as diarrhea may occur in pneumonia caused by Chlamydia or Legionella spp. A dry cough, an earache, aural discharge, and occasionally the presence of altered mental status may suggest pneumonia caused by M pneumoniae. Headache is common in patients with Legionella pneumonia. Patients with Chlamydia pneumonia may have a protracted upper respiratory infection with laryngitis that resembles a viral infection.
On examination, patients with a mild infection may not have acute distress, whereas patients with severe pneumonia often have severe respiratory distress and may appear toxic. The most common signs of pneumonia are tachycardia (heart rate >100/min) and tachypnea. Temperature is commonly elevated but does not have a specific pattern. Pulse-temperature dissociation may be noted in viral, Legionella, mycoplasmal, or chlamydial pneumonia. To decrease pleuritic pain, splinting of the involved side may be noted. Pulmonary auscultation reveals crepitations and rhonchi. Signs of consolidation, such as dullness to percussion, increased vocal fremitus, bronchial breath sounds, and egophony, may be present. Signs of lobar consolidation are more likely in bacterial pneumonia. A pleural effusion may be detected. Use of accessory respiratory muscles, cyanosis, confusion, and severe tachypnea indicates severe respiratory distress. Hypotension and circulatory collapse occur in severe cases.
Assessment of the severity of infection and need for hospitalization must be done for all patients. Certain clinical signs predict higher morbidity and mortality. These include respiration rate >30 breaths/ min, diastolic blood pressure ≤60 mm Hg or a systolic blood pressure ≤90 mm Hg, temperature ≥38.3°C, extrapulmonary complications (such as the presence of septic arthritis or meningitis), confusion and altered mental status, requirement for vasopressors for >4 h, need for mechanical ventilation, decreased urine output to < 20 mL/h or total urine output < 80 mL in 4 h (except in patients with chronic renal disease), or acute renal failure. Occasionally, physical signs may suggest specific etiology such as bullous myringitis, central nervous system symptoms, or erythema multiforme in M pneumoniae infection; erythema nodosum is associated with C pneumoniae, M tuberculosis, or fungal infections. Physical findings among patients with Mycoplasma, P carinii, or viral pneumonia may be minimal despite significant changes on the chest radiographs. Pulmonary histoplasmosis may be associated with oral ulcers and is frequent among patients with AIDS.
Gram stain examination and culture of sputum should be done in most outpatients and in all hospitalized patients. Sputum Gram stain provides a rapid and inexpensive method for a microbiologic diagnosis and aids in the selection of an appropriate management of pneumonia. A satisfactory sputum specimen is one that has < 10 epithelial cells and >25 neutrophils in a low power (× 100) field. Sputum specimens that do not meet these strict criteria should be rejected for culture and the Gram stain results disregarded. For optimum sputum collection, patients must be alert and able to follow instructions. They should first rinse their mouths with water to decrease the oropharyngeal contamination and then collect expectorated material from a deep cough. Induced sputum is a more appropriate sample in patients unable to expectorate. Sputum induction is done with hypertonic saline aerosol. This method is useful for the diagnosis of P carinii pneumonia, M tuberculosis, or fungal disease.
Interpretation of the Gram stain of a sputum sample is dependent on knowledge of the normal flora of the mouth. Normal mouth flora includes abundant aerobic and anaerobic bacteria. Asymptomatic patients frequently harbor potentially pathogenic bacteria such as S pneumoniae, H influenzae, S aureus, and N meningitidis in the oropharynx. In healthy persons, ≤9% are colonized with S pneumoniae, and the carrier rate is higher in persons with preschool-aged children. Colonization with S aureus and gram-negative bacilli increases after 2 weeks of hospitalization and is frequent among nursing home residents and patients with chronic illnesses such as alcoholism, diabetes, or malignancies. Oropharyngeal colonization by gram-negative organisms increases the likelihood of a gram-negative bacillary pneumonia. However, isolation of gram-negative bacilli from sputum does not always implicate these organisms as the etiologic agent. Similarly, although Candida spp. are frequently recovered from sputa of normal individuals or from patients in intensive-care units, it rarely if ever causes LRTI.
Direct examination of the sputum is done by a Gram stain, by special stains such as acid fast (AFB) or KOH stain, or by immunofluorescence. Predominance of an organism on the sputum Gram stain examination sometimes identifies the causative agent. Abundant pathogenic bacteria with a characteristic morphology, such as the small lancet-shaped gram-positive diplococci of S pneumoniae, gram-negative coccobacillary forms of H influenzae, or gram-negative cocci of M catarrhalis, help in making the diagnosis. Polymicrobial bacteria suggest anaerobic gram-negative bacillary or aspiration pneumonia. Using an adequate sputum specimen, the sensitivity and specificity of the Gram stain approaches 50–60% and >80% respectively, especially for S pneumoniae. Special stains must be performed on specimens to identify organisms not ordinarily seen on the Gram stain. P carinii is identified by using either methenamine silver staining or fluorescent Calcofluor stain. Mycobacteria are visualized with AFB, Kinyoun stain, or fluorescent auramine rhodamine stain. Modified AFB is required for the detection of Nocardia spp. Direct fluorescent antibody stains may detect Legionella spp.; KOH preparations may be necessary to identify fungi such as Histoplasma, Blastomyces, or Coccidioides.
Sputum cultures are not as sensitive or specific as Gram stains and are likely to be nondiagnostic in 50% of instances despite a highly suggestive Gram stain. In bacteremic pneumococcal pneumonia, only 40–50% of cases have a positive sputum culture for S pneumoniae. The recovery of some microorganisms from sputum culture usually implies their definitive role in pneumonia, and they do not usually represent contamination. These organisms include L pneumophila, M tuberculosis, H capsulatum, Coccidioides immitis, Cryptococcus neoformans, Blastomyces spp., C burnetii, Nocardia spp., Francisella tularensis, and Yersinia pestis. Anaerobic cultures of sputum are of no value owing to oropharyngeal contamination. M pneumoniae isolation from sputum cultures is technically difficult, and it may take ≤30 days to grow the microorganism.
Direct immunofluorescence assay (DFA) and EIA of sputum are useful in rapid diagnosis. DFA can detect Legionella spp. in respiratory secretions from 25% to 75% of patients with pneumonia caused by this organism. The sensitivity of the DFA varies with the antibody used, pathogenic species, and expertise of the personnel performing the test. Throat or nasopharyngeal swabs are the preferred specimens for DFA and cultures in suspected viral or Chlamydia pneumonia. DFA for C trachomatis has a sensitivity of 90%. Antigen detection tests for influenza A and B, parainfluenza, and RSV viruses have a sensitivity of 80%. DFA for RSV is more sensitive than cultures.
Blood cultures should be obtained from all hospitalized patients with pneumonia. Bacteremia occurs in 20–30% of patients with pneumococcal pneumonia.
Positive blood cultures have a high specificity in providing a definitive diagnosis. Blood cultures are particularly useful in chronically ill, immunocompromised patients and in patients with a history of alcoholism or malignancies. Positive cultures from other infected body fluids such as pleural, joint, or cerebrospinal fluid also may be diagnostic.
Thoracentesis should be performed in patients with a pleural effusion who are not responding to appropriate antibiotics, or in seriously ill patients who are suspected of having empyema. Small pleural effusions should be considered for aspiration if fever persists for >3 days on appropriate antimicrobial therapy. Pleural effusions occur more frequently in infections caused by group A streptococci, gram-negative bacilli, anaerobes, S aureus, or S pneumoniae. Pleural fluid should be promptly analyzed for pH, glucose, protein, and lactate dehydrogenase (LDH) and should be Gram stained and cultured for bacteria, mycobacteria, and fungi.
Serologies are not helpful in rapid etiologic diagnosis of pneumonia. They may be important in hospitalized patients with undiagnosed pneumonia, in which serology may be the only practical way to diagnose infections such as hantavirus or Q fever. Serologic tests are available for Chlamydia spp., Legionella spp., Mycoplasma spp., C burnetii, leptospirosis, and viruses such as influenza A and B, parainfluenza, RSV, adenovirus, hantavirus, CMV, herpesvirus, and varicella virus. Serologies may be useful for the diagnosis of histoplasmosis, coccidioidomycosis, blastomycosis, and cryptococcal pneumonia. Serologic diagnosis must be confirmed with an appropriate clinical picture and a positive IgM or a fourfold increase or decrease in the IgG titer in paired sera. A negative serology does not exclude the presumptive diagnosis. Delay in diagnosis and cost are the major disadvantages of serologic testing. Serologies are not practical or cost-effective in outpatient pneumonia.
Antigen detection by EIA, counterimmunoelectrophoresis, bacterial antigen test, or radioimmunoassay may be used to detect S pneumoniae, H influenzae, or L pneumophila. Urine, pleural fluid, or cerebrospinal fluid may be used to detect pneumococcal antigens. Pneumococcal antigen detection has the highest yield in sputum and persists for an extended period of time after an acute infection. Rapid EIA detection of RSV, influenza virus, or parainfluenza viruses has a sensitivity of >80% and is useful in clinical practice. EIA detection of L pneumophila serogroup I antigen in urine may provide a rapid diagnosis. EIA has a 70–80% sensitivity and a specificity of >95%, but the test currently detects only serogroup I. Legionella antigenuria persists for a considerable length of time after the initial infection. The presence of cold agglutinins in serum is insensitive (sensitivity of 30–60%) and nonspecific for the diagnosis of M pneumoniae infection.
Patients with unexplained pulmonary infiltrates who fail empiric therapy, have a fulminant clinical course, are immunocompromised, or are mechanically ventilated should be considered for fiber optic bronchoscopic examination and quantitative bronchoalveolar lavage (BAL) or sample collection with the protected specimen brush (PSB). Bronchoscopic aspiration with PSB has a sensitivity of 70–97% and a specificity of 95–100% in the diagnosis of bacterial pneumonia. Gram staining of the bronchoscopic specimen is important in early presumptive diagnosis and, when positive, predicts growth of >103organisms/mL. A BAL specimen is considered diagnostic if it has 103–105 cfu/mL growth of bacteria, especially if the Gram stain shows >25 neutrophils and < 1% squamous cells. The diagnostic yield may be slightly less than with PSB. BAL is particularly helpful in the diagnosis of P carinii pneumonia (sensitivity of >95%). Detection of CMV and M tuberculosis increases with BAL. Antibiotic use or a history of pulmonary diseases such as chronic bronchitis or cystic fibrosis decreases the diagnostic yield from bronchoscopic specimens.
Occasionally, fine-needle lung aspiration, transbronchial biopsy, or open-lung biopsy may be necessary for diagnosis. The risk of bleeding and pneumothorax (~20%) and variable diagnostic yields have decreased the utility of fine-needle lung aspiration. The diagnostic yield of a transbronchial biopsy is low. Thoracoscopic evaluation of the pleura and underlying lung is useful for the diagnosis of M tuberculosis infection, particularly when done in conjunction with a pleural biopsy. Finally, open-lung biopsy may be necessary when other procedures fail to yield a diagnosis. Open-lung biopsy is important in severely ill, immunocompromised patients or in patients not responding to empiric therapy. The diagnostic yield varies from 60% to 100%. The tissue should be examined for histopathology, Gram stained for bacteria, stained for acid fast bacilli, fungi, and Legionella spp., and cultured for these organisms. The lung tissue can also be subjected to molecular analysis by DNA probes or polymerase chain reaction techniques for rapid diagnoses of bacteria including mycobacteria, C pneumoniae, Legionella spp., or viruses. Open-lung biopsy alone may be useful for the diagnosis of noninfectious conditions such as malignancy, hemorrhage, vasculitis, bronchiolitis obliterans, drug-induced pulmonary injury, and others.
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Figure 10-2. Round pneumonia. Round opacification is seen in the posterior right lower lobe with indistinct margins seen on (A) the posterior-anterior and (B) the lateral-view chest radiographs. Round pneumonia is mostly caused by S pneumoniae and is usually seen in children <8 years of age. |
Diffuse bilateral interstitial infiltrates are seen in pneumonias caused by P carinii or Legionella spp. and in viral, Mycoplasma, or Chlamydia pneumonia. These are usually present without a pleural effusion.
Differential Diagnosis
A large number of diseases and clinical syndromes can mimic pneumonia. These conditions include pulmonary manifestations of systemic vasculitis, hypersensitivity pneumonitis, bronchiolitis obliterans with organizing pneumonia, drug reactions, alveolar hemorrhage, chronic eosinophilic pneumonia, and pulmonary alveolar proteinosis. Malignancies or lymphoproliferative disorders can mimic CAP.
Distinguishing an infectious from a noninfectious etiology for pulmonary infiltrates may be difficult. The clues that suggest a noninfectious cause are an insidious onset, nonproductive cough, a relatively less toxic-appearing patient, a normal or only mildly elevated leukocyte count, and a lack of response to broad-spectrum-antibiotic therapy. The presence of extrapulmonary manifestations such as arthralgias or arthritis, rash, and multiorgan involvement in the absence of sepsis suggests a noninfectious process such as vasculitis.
An immune response to inhaled antigens results in pulmonary infiltration with lymphocytes, plasma cells, eosinophils, and neutrophils, with the development of sarcoidlike granulomas in the airways and pulmonary parenchyma, called hypersensitivity pneumonitis. Establishing a compatible exposure history, usually to farm animals or plants, suggests the diagnosis of hypersensitivity pneumonitis. Specific examples include thermophilic Actinomyces infection (eg, farmer's lung), fungi (maltworker's lung), or avian protein antigens (pigeon breeder's lung). Symptoms of hypersensitivity pneumonitis usually resolve within 24–48 h after removal of the offending antigen. Chest radiographic features and high-resolution chest computed tomography (CT) reveal bilateral mixed interstitial and alveolar infiltrates with some fibrosis in chronic cases. Of patients with chronic eosinophilic pneumonia, 60–80% present with radiographic findings of peripheral infiltrates with central clearing. Transbronchial biopsy and presence of eosinophilia, often >40% in BAL fluid, establish the diagnosis. Bronchiolitis obliterans-organizing pneumonia is suspected in patients presenting with a clinical picture similar to CAP that does not respond to antimicrobial therapy. Chest radiographs demonstrate multifocal segmental or lobar alveolar infiltrates with air bronchograms in 60–80% of patients. There may be a peripheral predilection for pulmonary infiltrates similar to chronic eosinophilic pneumonia; 20–30% of patients have reticulonodular infiltrates. Although open-lung biopsy is considered the most effective test for the diagnosis of bronchiolitis obliterans-organizing pneumonia, occasionally transbronchial biopsy may establish the diagnosis. Drug-induced acute pneumonitis caused by nitrofurantoin, amiodarone, methotrexate, and other drugs should be considered in the differential diagnosis of CAP that does not respond to antimicrobial therapy. Systemic vasculitis may affect the lung, either primarily or as part of multiorgan involvement. Wegener's granulomatosis and Churg-Strauss syndrome are granulomatous forms of vasculitis that have a striking affinity for lung manifestations. Pulmonary cavitation and severe extrapulmonary symptoms such as upper-airway, renal, or ocular symptoms suggest Wegener's granulomatosis. Although serum antineutrophil cytoplasmic antibody (ANCA), especially c-ANCA (diffuse granular cytoplasmic staining pattern), has a reported sensitivity of >90% in patients with Wegener's granulomatosis, biopsies of involved organs are essential to confirm the diagnosis. Diagnosis of alveolar hemorrhage is supported by anemia and bronchoscopic evidence of blood-tinged BAL fluid with hemosiderin-laden macrophages.
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Figure 10-3. Pneumococcal pneumonia. (A) Posterior-anterior and (B) lateral views show opacification of the anterior and posterior segments of the right upper and middle lobes. Right lower lobe is not involved. |
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Figure 10-4. Blastomycosis in an immunocompromised host. Diffuse nodular interstitial pulmonary infiltrates. Open-lung biopsy confirmed granulomatous pneumonia with budding yeast forms and subsequent positive cultures for Blastomyces dermatitidis. |
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Figure 10-5. Miliary tuberculosis. Diffuse reticular-nodular bilateral pulmonary infiltrates. |
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Figure 10-6. Aspergilloma. Large elongated cavitary mass in the right mid lung with central opacification and a crescent of lucency superiorly. |
Other conditions that simulate CAP include pulmonary embolism, which may present with cough, fever, and chest pain. Clinical history, physical findings such as calf tenderness, and the rapidity of onset of symptoms should suggest pulmonary embolism.
Complications
Pleural effusion and empyema are potential complications and may cause failure to respond to appropriate therapy. Lung abscess is another suppurative complication that can occur among patients, particularly after aspiration or in the presence of a pulmonary structural problem such as a malignancy. Patients can develop respiratory failure with or without septic shock and subsequent death. Respiratory failure and shock are more likely to occur in elderly, diabetic, alcoholic, or immunocompromised patients. Preexisting pulmonary disease is a risk factor for respiratory failure and ventilatory support. Young infants with RSV pneumonia can develop hyperactive airway disease later in childhood. Occasionally, P carinii pneumonia is associated with spontaneous pneumothorax.
Treatment
Severity of illness and risk factor assessment is essential in evaluating a patient for outpatient therapy compared with hospitalization. The presence of coexisting illnesses, immunosuppression, respiratory rate of >30/min, hypotension, multilobar involvement, hypoxemia, acidosis, electrolyte abnormalities, leukopenia (leukocytes < 4.0/mm3) or leukocytosis (leukocytes >20/mm3) are indices of severe pneumonia that warrant hospitalization. This assessment should be conducted expeditiously, because these patients can progress rapidly to circulatory collapse and respiratory distress necessitating mechanical ventilation. They should receive immediate antimicrobial therapy, because delay in onset of antimicrobial therapy may increase morbidity and mortality. Patients with some but not all of the poor prognostic signs may also warrant admission to a hospital, but not necessarily to an intensive-care unit. Patients without any underlying comorbidity and with normal or mildly abnormal physical findings represent low-risk individuals who may be treated with antimicrobial therapy as outpatients.
In addition to risk factors and objective findings, such factors as patient compliance and competence and the presence of a caregiver at home should be considered in making the decision for outpatient versus inpatient care. Patients with minimal or no home support may warrant hospitalization until outpatient support can be organized.
The choice of empiric antimicrobial therapy depends on the severity of disease, host factors, likely microorganism(s), epidemiological factors, and local antimicrobial resistance patterns. For instance, patients with a history of structural lung disease (cystic fibrosis, bronchiectasis) or nursing home residents require therapy with an antipseudomonal antibiotic (ceftazidime, cefepime, or antipseudomonal penicillin, or a carbapenem or fluoroquinolone). Aztreonam and a fluoroquinolone with or without an aminoglycoside are antibiotic options for β-lactam–allergic patients with gram-negative bacilli or NAP.
Doxycycline is appropriate therapy for younger (17- to 40-year-old) individuals with pneumonia because of the likelihood of M pneumonia infection.
Broad spectrum empirical antimicrobial therapy of severe CAP should also include therapy against atypical organisms such as Legionella. Co-administration of a macrolide or a fluoroquinolone together with a β-lactam antibiotic (a third- or fourth-generation cephalosporin such as cefotaxime, ceftriaxone, or cefepime; or piperacillin/tazobactam) has been shown to decrease mortality in patients with severe CAP. Monotherapy with either a macrolide or a fluoroquinolone are not recommended in such patients. Patients with severe CAP with underlying chronic structural lung disease, frequent hospitalizations, or history of long-term care facility stay, the use of antimicrobials with anti-pseudomonal activity (such as cefepime, ceftazidime, or a fluoroquinolone with enhanced activity against S pneumoniae and P aeruginosa such as levofloxacin or gatifloxacin) is recommended.
Empiric antibiotic therapy may be modified once identification of a specific microorganism(s) and its susceptibilities is available. Parenteral penicillin G is the drug of choice for in-patient penicillin-susceptible pneumococcal pneumonia. Studies demonstrate that S pneumoniae strains that are penicillin-susceptible and intermediately penicillin-resistant (minimal inhibitory concentration < 2 µg/mL) may be treated with a penicillin or a third-generation cephalosporin such as ceftriaxone or cefotaxime. Penicillin-resistant pneumococcal pneumonia may be successfully treated with high-dose penicillin or a third-generation cephalosporin, vancomycin, a fluoroquinolone such as levofloxacin or gatifloxacin, or a carbapenem such as imipenem/cilastin or meropenem.
A second- or third-generation cephalosporin; β-lactam/β-lactamase inhibitor antibiotics such as amoxicillin/clavulanate, ampicillin/sulbactam, and piperacillin/tazobactam; carbapenems such as imipenem or meropenem; macrolides such as azithromycin; and fluoroquinolones are effective therapy for CAP caused by H influenzae or M catarrhalis.
C pneumoniae, M pneumoniae, and Legionella pneumonia respond to therapy with a tetracycline, macrolide, or fluoroquinolone. Rifampin is active in vitro against L pneumophila and may be used as adjunctive therapy for severe Legionella pneumonia.
Parenteral therapy with either a fluoroquinolone or high-dose erythromycin is recommended for moderate to severe Legionella pneumonia. Azithromycin and clarithromycin are more active in vitro than erythromycin against L pneumophila. Treatment failures have been reported with erythromycin. Oral therapy with azithromycin or clarithromycin or with a fluoroquinolone such as ciprofloxacin, ofloxacin, or levofloxacin may be considered for mild to moderate infection. There is no evidence to suggest that the addition of rifampin or erythromycin to fluoroquinolone therapy is more effective than a fluoroquinolone used alone. Therapy is usually continued for 3 weeks for Legionella pneumonia.
Parenterally administered antibiotics should be switched to oral therapy once the patient has demonstrated clinical response, is hemodynamically stable, is able to tolerate medications administered orally, and has no evidence of malabsorption. The switch from parenteral to oral antibiotics also depends on the availability of an oral equivalent of the parenteral drug being administered.
Most patients defervesce and show improvement of cough, tachycardia, and tachypnea within 3–5 days of onset of effective antimicrobial therapy. Patients with bacteremic pneumococcal pneumonia or with Legionella pneumonia usually take longer to improve (6–7 days). The optimum duration of antimicrobial therapy for CAP has not been studied in controlled clinical trials. Most studies have administered antimicrobial therapy for 10–14 days. Studies have demonstrated that a 5-day course of azithromycin is effective for outpatient CAP.
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BOX 10-13A Empiric Outpatient Antimicrobial Therapy of Community-Acquired Pneumonia |
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BOX 10-13B Empiric Antimicrobial Therapy of Community-Acquired Pneumonia Requiring Hospitalization (Non-ICU) |
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BOX 10-13C Empiric Antimicrobial Therapy of Community-Acquired Pneumonia Requiring Intensive Care Unit |
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BOX 10-14 Empiric Antimicrobial Therapy of Nosocomially Acquired Pneumonia1 |
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BOX 10-15 Empiric Antimicrobial Therapy of Infections in Patients with Cystic Fibrosis1 |
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Prognosis
Pneumonia is associated with an average mortality rate of 14% in hospitalized patients and an estimated mortality of < 1% in nonhospitalized patients. Mortality from pneumococcal pneumonia among patients >60 years of age varies from 5% to 25% and is ~20% in bacteremic pneumococcal pneumonia. It is the sixth most common cause of death in the United States. Risk factors for increased mortality include extremes of age and underlying diseases such as malignancy, diabetes, chronic lung disease, chronic renal failure, alcoholism, immunosuppression, congestive heart failure, and neurological disease. Previous episodes of pneumonia contribute to higher mortality. Gram-negative bacilli, S aureus, or polymicrobial pneumonia, as in aspiration or postobstructive pneumonia, are associated with a higher mortality. Asplenia and severe malnutrition are also associated with a high mortality.
Prevention
The pneumococcal vaccine has an efficacy of >60% in preventing bacteremic pneumococcal infection caused by vaccine strain bacteria and reduction of severity in immunocompetent patients, but this rate declines with advancing age and immunosuppression. Pneumococcal vaccine is repeated once in 6 years for asplenic patients and for patients >65 years old who received their initial dose before the age of 65 years.
Appropriate identification and decontamination of water sources may prevent Legionella pneumonia. Control measures include hyperchlorination of water supplies and decontamination of air-conditioning cooling units.
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BOX 10-16 Control of Community-Acquired Pneumonia |
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BOX 10-17 Control of Nosocomially Acquired Pneumonia |
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BOX 10-18 Control of Infections in Patients with Cystic Fibrosis |
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PARAPNEUMONIC EFFUSION & PLEURAL EMPYEMA
Essentials of Diagnosis
General Considerations
A parapneumonic effusion is defined as a pleural effusion that occurs secondary to a pulmonary infection. An empyema is defined as a collection of pus in a normally sterile body cavity, such as between the visceral and parietal pleurae. Empyema usually results from contiguous spread of an infection from the lung or other neighboring sites.
The pleural space is a sterile space, which normally contains a scant amount of fluid, between the visceral and parietal pleurae. The pleural space is a relatively immunodeficient space, because it does not contain a high number of phagocytes and lacks opsonins and complements.
Microorganisms enter the pleural space either by contiguous spread from an infected lung, perforated esophagus, mediastinum, or subdiaphragmatic structures or by direct entry as a result of trauma, thoracic surgery, or thoracentesis. The most common cause of a parapneumonic effusion or empyema is an underlying pneumonia. Less often, infection may spread from a retropharyngeal, retroperitoneal, vertebral, or paravertebral source. Once bacteria enter the pleural space, an inflammatory response results in migration of PMN leukocytes and induction of cytokines such as TNF. Because of the relative inefficiency of the defense mechanisms in the pleural space, the bacteria multiply rapidly. This leads to a fibrinopurulent effusion with increased chemotaxis of PMN leukocytes, increased inflammatory response, fibrin deposition, and loculations. With increasing bacterial growth, accumulation and lysis of inflammatory cells, the fluid pH, and glucose levels decrease, and LDH increases. This may be followed by fibroblast proliferation and scar formation.
The response to adjacent infection may result in either a parapneumonic effusion or an empyema. Parapneumonic effusions are classified by size and laboratory parameters. Small (< 10-mm-thick effusion on a decubitus radiograph) or larger effusions that have glucose >40 mg/dL, pH >7.00, and LDH < 1000 IU/L and that are culture-negative are considered parapneumonic effusions. These effusions usually respond to antibiotic therapy and require no surgical intervention. Empyema is defined by positive Gram stain or cultures, glucose < 40 mg/dL, pH < 7.00, and multiloculated collections of pus.
The microbiology of empyema depends on the source of infection and host factors (Box 10-19). Because an empyema usually is a complication of pneumonia, S pneumoniae, S aureus, and streptococci are the most common organisms isolated. S aureus is a common cause of empyema, particularly in children < 6 months of age or in postsurgical or trauma patients, and it occasionally occurs in association with hemothorax. Overall, S aureus accounts for 29–35% of all cases of pediatric empyema. In older children, S pneumoniae, S aureus, and H influenzae most often cause empyema. Aerobic gram-negative bacilli may cause empyema in alcoholics or after thoracic surgery or trauma not confined to alcoholics. Postsurgical or traumatic empyema may also be caused by S aureus, a polymicrobial infection, or, rarely, by Aspergillus spp. Polymicrobial empyema may result from aspiration pneumonia, lung abscess, or perforation of the esophagus or stomach. Anaerobic empyema is uncommon in young children < 6 years of age. An empyema can develop as an extension of a subdiaphragmatic abscess. Less common etiologies of empyema include M tuberculosis, C neoformans, C immitis, rupture of an echinococcal cyst, or an Entamoeba histolyticaliver abscess that ruptures into the pleural cavity. Rarely, an empyema may erode and drain spontaneously through the chest wall. This condition is called empyema necessitatis and is typically associated with Actinomyces, Nocardia spp., or M tuberculosis.
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BOX 10-19 Microbiology of Empyema |
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Clinical Findings
Differential Diagnosis
Noninfectious causes of pleural effusion must be differentiated for accurate therapy and response. Exudative effusions may result from congestive heart failure, malignancies, collagen vascular diseases, thoracic duct tears, or pancreatitis. Malignant effusion is often hemorrhagic and may be differentiated by cytological evaluation of the pleural fluid.
Complications
In children, empyema may result in pneumatoceles, pneumothorax, or scoliosis as a result of scarring.
Other complications result from the local spread of infection to surrounding structures such as the lung, pericardium, and myocardium. Some patients develop a severe, overwhelming infection that results in multisystem organ failure and death. Empyema-associated mortality is low and varies from 1% to 19%. Mortality increases with age >50 years, immunosuppression, comorbidities, and NAP.
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Figure 10-7. Empyema. Large, homogenous broad-based density against the left posterior chest wall. There are left lower lobe infiltrates as well. A. Posterior-anterior view. B. Lateral view. |
Treatment
Gross appearance, biochemical composition, and the radiographic appearance of the fluid guide the management of an infected effusion. The goals of treatment include appropriate antimicrobial therapy, removal of infected fluid, and re-expansion of the underlying lung.
Empiric antimicrobial therapy depends on the putative etiology of parapneumonic effusion or empyema (Box 10-20). When it is the result of CAP, empiric antimicrobial therapy should be directed against S pneumoniae, and the use of a third-generation cephalosporin is appropriate. A specific antimicrobial agent may be administered for known pathogens recovered from the sputum, blood, or pleural fluid. Broad-spectrum antimicrobial therapy is indicated if the empyema is thought to be caused by a ruptured lung abscess, postobstructive pneumonia from an endobronchial lesion, postoperative complication, trauma, or a nosocomial infection. In such situations, therapy should include a drug or combination of drugs with activity against gram-negative bacilli, gram-positive cocci, and anaerobes. Duration of antimicrobial therapy is usually 4–6 weeks.
Parapneumonic effusions with pH >7.20 should be treated with antimicrobial therapy and drainage. Parapneumonic effusions with pH between 7.0 and 7.20 and elevated LDH may require repeated thoracentesis or chest tube drainage, together with antimicrobial therapy. Chest tube drainage, open drainage, or decortication is required for adequate therapy of empyema.
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BOX 10-20 Empiric Therapy of Empyema1 |
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Prognosis
The prognosis is extremely good, with cure rates of >90% for uncomplicated parapneumonic effusions when treated with an appropriate antimicrobial agent and with drainage as necessary. Patients with loculated pleural effusions or leukocyte counts of < 6400 are associated with treatment failure if not managed with nonsurgical measures. With the advent of surgical and nonsurgical intervention techniques and the vast majority of antimicrobial agents, mortality from empyema is low, ranging from 4% to 10%. Mortality varies with the causative organisms, such as Aspergillus species, underlying risk factors such as malignancy or other comorbid conditions, older age, and delay in appropriate therapy. Chronic empyema with a thick pleural wall requires a surgical approach. These types of empyema may take months to resolve and are more likely to result in treatment failures.
Prevention
Early administration of effective antimicrobial therapy for LRTIs and early recognition and drainage of infected parapneumonic effusions are most important for the prevention of empyema (Box 10-21). Careful closure and inspection of the bronchial stump after pneumonectomy may prevent empyema that results from a postoperative bronchopleural fistula.
LUNG ABSCESS
Essentials of Diagnosis
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BOX 10-21 Control of Empyema |
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General Considerations
Lung abscess is defined as an acute or chronic suppurative infection of the lung parenchyma caused by a single microorganism or multiple microorganisms, predominantly oral anaerobes, that results in destruction of the lung tissue and eventual cavity formation. Lung abscesses are classified as primary or secondary, depending on the pathogenesis and host factors. Primary lung abscesses occur because of aspiration or as the result of an infection of the lung caused by virulent organisms. Lung abscesses may be caused by microorganisms that cavitate, such as Nocardia spp., M tuberculosis, S aureus, or S pyogenes. Primary lung abscesses occur more frequently than secondary abscesses. Secondary lung abscesses are those that occur as a result of a remote primary infection with bacteremic spread to the lung or as an extension from a subphrenic abscess. Secondary infections may also include bacterial superinfection after a pulmonary infarct or as a complication of an underlying process, such as an endobronchial lesion or bronchiectasis.
Aspiration of infectious material is the most common cause of lung abscesses. Oropharyngeal fluid containing multiple aerobic and anaerobic microorganisms is aspirated and carried to the most dependent portions of the lung, which are usually the right upper lobe or the superior segment of the right lower lobe. However, other parts of the lung may be involved. After the initial localized pneumonitis, there is bacterial proliferation, extensive inflammation, necrosis, and destruction of the lung tissue. This destruction may erode into a bronchiole or bronchus, leading to expectoration and partial emptying of the cavity, which creates an air-fluid level. The lung abscess may involve the pleural space by rupture or direct extension.
The microbiology of lung abscesses varies by the cause (Box 10-22). Because aspiration is the most common cause, it results in a polymicrobial infection that includes gram-negative bacilli, gram-positive cocci, and anaerobes. Anaerobes encountered in lung abscesses are oral anaerobic gram-negative bacilli and gram-positive cocci or bacilli. Anaerobes that are commonly isolated include Prevotella spp., Bacteroides spp., Fusobacterium spp., Peptostreptococcus spp., Clostridium spp., and, rarely, Actinomyces spp. Aerobic gram-negative bacilli such as K pneumoniae, Enterobacter spp., or P aeruginosa, along with anaerobes, predominate among nursing home residents with NAP, alcoholics, and trauma patients. Patients with lung abscesses tend to have poor oral hygiene and dental and gingival disease. Lung abscesses occur less commonly in edentulous patients. Lung abscess may develop from a metastatic infection as seen with Fusobacterium necrophorum septicemia or thrombophlebitis complicating an anaerobic pharyngitis (Vincent's angina, Lemierre's syndrome).
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BOX 10-22 Microbiology of Lung Abscess |
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A process similar to lung abscess is a severe nonlocalized necrotizing pneumonia caused by anaerobic or aerobic bacteria, involving one or more lobes, that presents as severe pneumonia and multiple small cavities. Anaerobic bacteria and S aureus are the most common causes of necrotizing pneumonia. Other microorganisms that may cause necrotizing pneumonia include S pyogenes, gram-negative bacilli such as Proteus spp., or, rarely, Legionella spp. S aureus is the most common cause of bacteremic spread to the lungs that results in multiple lung abscesses.
Fungi may also cause lung abscesses and include Aspergillus spp., C immitis, B dermatitidis, and H capsulatum. Unusual causes of lung abscess include Rhodococcus equi and nontyphi strains of Salmonella spp.
Lung abscesses may result from direct extension of an intra-abdominal process. Examples of this include the direct extension of an amebic liver abscess or subphrenic abscesses.
The microbiology of lung abscess in children differs from that of adults. The most common cause of lung abscess in children is S aureus, followed by S pyogenes, H influenzae, and S pneumoniae. Abscesses in children may be polymicrobial and include anaerobes. In neonates, lung abscesses are usually caused by gram-negative bacilli.
Clinical Findings
Examination often reveals a chronically ill-appearing patient with poor dental hygiene, signs of neurologic disorder with an impaired gag reflex, and putrid-smelling expectorated sputum. Clubbing of the fingers may be present. Pulmonary examination is similar to that of patients with pneumonia. Breath sounds overlying the cavity may be bronchial in character, with an intense, high-pitched tone called “amphoric breathing.” However, if the cavity is completely filled, breath sounds may be faint or absent. There may be signs of consolidation with dullness to percussion, increased vocal and tactile fremitus, and bronchial breath sounds. A pleural effusion may be present. Signs of an underlying condition may be present, such as spider naevi, palmar erythema, and splenomegaly suggestive of hepatic cirrhosis.
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Figure 10-8. Cavitary coccidioidomycosis. Thin-walled cavities in the right upper lobe with adjacent pleural thickening and infiltrative process in a frequent traveler to the southwest United States. Sputum culture was positive for Coccidioides immitis. |
Differential Diagnosis
Wegener's granulomatosis, bronchogenic carcinoma, or a metastatic malignancy may cause cavitary lung infiltrates. Echinococcal cysts, Paragonimus westermani infection, emphysematous bullae, or a pulmonary infarct may be mistaken for a lung abscess. Occasionally, an empyema may be difficult to differentiate from a lung abscess in chest radiographs.
Complications
Complications of lung abscess primarily result from direct extension of infection into neighboring structures. Pleura-based lung abscesses may extend into the pleural cavity and result in an empyema, which occurs in about one-third of patients with a lung abscess. Bronchopleural fistula with resultant pyopneumothorax may occur. Some abscesses that are in close proximity to a large pulmonary vessel may erode into the vessel and cause massive or fatal hemorrhage. Systemic dissemination of infection to other locations, such as the brain, may occur.
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Figure 10-9. Cavitary blastomycosis. Left upper lung cavitary lesion. |
Treatment
The principles of treatment for a lung abscess are the same as for abscesses elsewhere in the body—effective antimicrobial therapy and drainage.
Initial empiric antibiotic therapy should be directed against polymicrobial oropharyngeal flora, especially anaerobes (Box 10-23). This may be achieved with either a combination of a parenteral penicillin or a third-generation cephalosporin with clindamycin or metronidazole; or a β-lactam/β-lactamase inhibitor combination such as piperacillin/tazobactam or ampicillin/sulbactam. Alcoholics, nursing home residents, or patients with a nosocomially acquired lung abscess should receive therapy with a third- or fourth-generation cephalosporin with antipseudomonal activity, such as ceftazidime or cefepime, together with clindamycin or metronidazole; or a β-lactam/β-lactamase inhibitor combination or a carbapenem (imipenem or meropenem); or a fluoroquinolone such as levofloxacin or ciprofloxacin together with clindamycin or metronidazole. The duration of antibiotic therapy is usually 4–6 weeks, with reassessment at intervals for complications or lack of response. Clinical improvement is usually apparent within 1–2 weeks; however, there is a delay of ≤8–12 weeks before resolution of the cavity occurs on chest radiograph or CT scan.
Medical therapy is effective in 80–90% of patients with a lung abscess < 5 cm in diameter. The majority of lung abscesses spontaneously drain into a bronchus. Postural drainage is strongly encouraged, and this may be improved with chest physiotherapy. Patients who do not respond to medical therapy or those with enlarging cavity size, ongoing sepsis, or associated empyema require drainage. Drainage of the lung abscess can be performed with transthoracic radiographic guidance or with open surgical drainage. Open surgical drainage is required in < 15% of patients. Indications for surgery include extent and severity of disease, underlying malignancy, large-volume hemoptysis, bronchopleural fistula with empyema, and inaccessibility of transthoracic drainage of the abscess.
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Figure 10-10. A and B. Chest radiograph of a patient with widened mediastinum and a right lower lobe cavitary infiltrate that is not clearly seen on the lateral view. C. CT of the chest shows the dilated esophagus in the posterior mediastinum, caused by achalasia in this patient. D. Magnified view of the CT shows the right lower lobe cavity caused by aspiration resulting from the achalasia. |
Prognosis
The prognosis of patients with lung abscesses depends on severity of disease, underlying host factors, and promptness of treatment. Poor prognostic indicators include a large cavity, multiple abscesses, abscesses caused by S aureus, P aeruginosa, or K pneumoniae, necrotizing pneumonia, and underlying host factors such as an immunocompromised status, including that caused by HIV infection, extremes of age, and malignancy. Overall, mortality from lung abscess is ~15%, and it increases to 25% with the presence of necrotizing pneumonia.
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BOX 10-23 Empiric Therapy of Lung Abscess1 |
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Prevention
It is important to identify patients susceptible to aspiration and to institute aspiration precautions promptly in these patients (Box 10-24). Lung abscess should be suspected in patients with a slow response or progression of infection despite appropriate therapy for CAP.
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BOX 10-24 Control of Lung Abscess |
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