Pneumonia

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Chapter 76

Pneumonia

Perspective

Pneumonia is the seventh leading cause of death and the leading cause of death from infectious disease in the United States.1 The annual incidence of community-acquired pneumonia (CAP) in the United States ranges from 2 to 4 million, resulting in approximately 500,000 hospital admissions. Most cases of CAP are managed in the outpatient setting and the mortality is low (approximately 1%), but pneumonia necessitating hospitalization is associated with a higher mortality rate (approximately 15%). Pneumonia remains challenging because of an expanding spectrum of pathogens, changing antibiotic resistance patterns, the continued introduction of newer antimicrobial agents, and increasing emphasis on cost-effectiveness and outpatient management.

The epidemiology of CAP is changing. As the percentage of the population older than 65 years continues to increase, the incidence of pneumonia is expected to increase. An increasing number of patients are taking immunosuppressive drugs related to treatment of malignancy, transplantation, or autoimmune disease, resulting in more cases of pneumonia from other opportunistic pathogens. Antibiotic resistance is more common among Streptococcus pneumoniae and other pathogens. In addition, the threat exists of respiratory infections caused by biologic terrorism or newly recognized pathogens that have the potential to spread quickly through international travel.

The ability to identify a specific cause of pneumonia during emergency department (ED) evaluation is limited. Even after a thorough inpatient evaluation, a specific pathogen is never identified in many patients with pneumonia. When pneumonia is diagnosed, the priorities in the ED are to initiate appropriate empirical antibiotic therapy based on the most likely pathogens, provide respiratory support, assess disease severity, and recognize the need for hospitalization and intensive care.

Principles of Disease

Despite the constant presence of potential pathogens in the respiratory tract, the lungs are remarkably resistant to infection. The alveolar surface of the lungs covers an area of approximately 140 m2. Approximately 10,000 L of air passes through the respiratory tract each day, and typical ambient air can contain hundreds to thousands of microorganisms per cubic meter. Although the cough and laryngeal reflexes prevent most large particulate matter from entering the lower respiratory tract, aspiration of oropharyngeal contents may be a common occurrence during normal sleep. Despite these hazards, healthy lungs are usually a virtually sterile environment.

The development of clinical pneumonia requires a defect in host defenses, the presence of a particularly virulent organism, or the introduction of a large inoculum of organisms. If the challenge of invading organisms overwhelms host defenses, then microbial proliferation leads to inflammation, an immune response, and clinical pneumonia. If host defenses are weak, then a minimal challenge may lead to the development of pneumonia.

Causative Agents

The challenge with pneumonia is identifying the causative agent rather than making the diagnosis in general. Empirical therapy should be chosen with activity against the spectrum of likely pathogens based on the overall clinical picture.

Difficulty in determining the specific cause of pneumonia exists even with advanced microbiologic and serologic testing that is not generally available during an ED evaluation. In CAP, a microbial cause cannot be determined in approximately half of cases, even after thorough investigation. Among hospitalized adults in whom a pathogen can be identified, organisms such as S. pneumoniae and Haemophilus influenzae, referred to as “typical” pathogens, account for approximately half of cases. Legionella, Mycoplasma, and Chlamydophila (previously known as Chlamydia) species, referred to as “atypical” pathogens, are also common.2 Testing for common viral agents reveals a viral cause in approximately 18% of cases, with influenza and parainfluenza viruses being the most common.3

Among adults requiring intensive care unit (ICU) admission, S. pneumoniae is the most common pathogen, with even higher prevalence among fatal cases. Legionella species, Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), and aerobic gram-negative bacilli also appear to be relatively more common among adults with severe CAP.4 Atypical organisms, such as Mycoplasma species or viruses, account for a relatively higher proportion of pneumonia in patients who have milder illness that is amenable to outpatient therapy.5 Atypical organisms occur with significant frequency, however, in patients with severe illness requiring hospitalization, particularly because of Legionella infection. Coinfection, such as with Chlamydophila pneumoniae and S. pneumoniae, is also well recognized.

S. pneumoniae is a gram-positive coccus that is the most common cause of CAP in adults requiring hospitalization. It colonizes the nasopharynx in 40% of healthy adults. Although this organism can cause pneumonia in healthy people, patients with a history of diabetes, cardiovascular disease, alcoholism, sickle cell disease, splenectomy, and malignancy or other immunosuppressive illness are at increased risk. A vaccine containing the 23 capsular polysaccharides of pneumococcal types most commonly associated with pneumonia reduces the likelihood of serious pneumococcal infection. It is recommended for people at increased risk because of underlying illness or age older than 65 years.6 Many ED patients have not received pneumococcal vaccine, and vaccinating eligible patients in this setting seems to be feasible and effective.7 A 13-valent protein-conjugate pneumococcal vaccine effectively reduces invasive pneumococcal disease and pneumonia in infants and young children.8

H. influenzae, the second most frequently isolated organism in CAP among adults, is a pleomorphic gram-negative rod. It is a common pathogen in adults with chronic obstructive pulmonary disease (COPD), alcoholism, malnutrition, malignancy, or diabetes.

S. aureus may be emerging as a more common cause of CAP and has been found more frequently than H. influenzae in some recent series. Community-associated strains of methicillin-resistant S. aureus (CA-MRSA) are uncommon in CAP but are more likely to cause severe disease.9 This is often associated with influenza. Staphylococcal pneumonias are often necrotizing, with cavitation and pneumatocele formation. Intravenous drug users may develop hematogenous spread of S. aureus that involves both lungs with multiple small infiltrates or abscesses (e.g., tricuspid endocarditis resulting in septic pulmonary emboli).

Klebsiella pneumoniae is a gram-negative rod that rarely causes disease in a normal host and accounts for a small percentage of cases of CAP. It may cause severe pneumonia in debilitated patients with alcoholism, diabetes, or other chronic illness. There is a high incidence of antibiotic resistance because the organism is often hospital acquired.

Mycoplasma pneumoniae is one of the most common causes of CAP in previously healthy patients younger than age 40 years. Another important organism in CAP is C. pneumoniae, an intracellular parasite that is transmitted between humans by respiratory secretions or aerosols. Seroprevalence studies indicate that virtually everyone is infected with C. pneumoniae at some time and that reinfection is common, particularly in older adults. It accounts for at least 8% of cases, although this is an underestimate owing to difficulty in diagnosing infection with this organism.

At least 30 species of Legionella have been isolated since the 1976 convention-related outbreak in Philadelphia, from which the organism derives its name. At least 19 are known human pathogens. Legionella is an intracellular organism that lives in aquatic environments. There is no person-to-person transmission. Although it is implicated in point outbreaks related to cooling towers and similar aquatic sources, the organism also lives in ordinary tap water and is underdiagnosed as a cause of CAP. Legionella prevalence seems to vary greatly by region.

Lower respiratory infections caused by anaerobic organisms generally result from the aspiration of oropharyngeal contents with large amounts of bacteria. These infections are typically polymicrobial, including Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella species. Presentation is often subacute or chronic and may be difficult to distinguish clinically from other causes of pneumonia. Clinical factors that suggest an anaerobic infection include risk factors for aspiration, such as central nervous system depression or swallowing dysfunction, severe periodontal disease, fetid sputum, and the presence of a pulmonary abscess or empyema.

Viral pneumonias are common in infants and young children and are recognized as an important cause of pneumonia in adults. Respiratory syncytial virus and parainfluenza viruses are the most common causes of pneumonia in infants and small children, occurring mostly during autumn and winter. Influenza viruses are the most common cause of viral pneumonia in adults. Winter influenza outbreaks, usually of influenza type A, may cause 40,000 deaths annually in the United States. More than 90% occur in people age 65 years or older.10 Metapneumovirus is a paramyxovirus that seems to be an important cause of viral pneumonia in children and adults.

Fungal infections caused by organisms such as Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis commonly manifest as pulmonary disease. These organisms are present in the soil in various geographic areas of the United States: H. capsulatum in the Mississippi and Ohio River valleys, C. immitis in desert areas of the Southwest, and B. dermatitidis in a poorly defined area extending beyond that of H. capsulatum. These infections should be considered in people in appropriate geographic areas, especially in those who are near activities that disturb the soil, such as construction or dirt bike riding, and in patients who do not respond to antibacterial antibiotics. Clinical presentation varies from an acute or chronic pneumonia to asymptomatic granulomas and hilar adenopathy.

Pneumocystis pneumonia (PCP) occurs in immunocompromised hosts, principally people with acquired immunodeficiency syndrome (AIDS) or malignancy. Pneumocystis jiroveci (previously known as Pneumocystis carinii) is one of the most common infections leading to a diagnosis of HIV infection and AIDS. Patients with pulmonary complaints should be questioned about HIV risk factors, and clinicians should search for signs of HIV-related immunosuppression, such as weight loss, lymphadenopathy, and oral thrush. PCP typically manifests subacutely with fatigue, exertional dyspnea, nonproductive cough, pleuritic chest pain, and fever.

Mycobacterium tuberculosis is a slow-growing bacterium transmitted between people by droplet nuclei produced from coughing and sneezing. M. tuberculosis survives within macrophages as a facultative intracellular parasite and may remain dormant in the body for many years. Active tuberculosis (TB) develops within 2 years of infection in approximately 5% of patients, and another 5% develop reactivation disease at some later time. Reactivation is more likely to occur in people with impaired cell-mediated immunity, such as patients with diabetes, renal failure, immunosuppressive therapy, malnutrition, or AIDS. Approximately one third of the world’s population is infected with M. tuberculosis. Approximately 8 million new cases of active disease develop annually, resulting in 3 million deaths worldwide. An estimated 10 to 15 million people in the United States (3-5% of the population) are infected with TB. Multidrug-resistant strains of M. tuberculosis are found in increasing numbers, especially among immigrants from Southeast Asia and AIDS patients.

Clinical Features

ED evaluation should focus on establishing the diagnosis of pneumonia and determining the presence of epidemiologic and clinical features that would influence decisions regarding hospitalization and antibiotics. Key history includes character of symptoms, setting in which the pneumonia is acquired, geographic or animal exposures, and host factors that predispose to certain types of infections and are associated with outcome.

Pneumonia generally manifests as a cough productive of purulent sputum, shortness of breath, and fever. In most healthy older children and adults, the diagnosis can be reasonably excluded on the basis of history and physical examination, with suspected cases confirmed by chest radiography. The absence of any abnormalities in vital signs or chest auscultation substantially reduces the likelihood of pneumonia as demonstrated by radiography. No single isolated clinical finding, however, is highly reliable in establishing or excluding a diagnosis of pneumonia.11

Elder or debilitated patients with pneumonia often have nonspecific complaints, such as acute confusion or a deterioration of baseline function, without classic symptoms. Elder patients are more likely to have advanced illness at the time of presentation and may have sepsis in the absence of a previous syndrome suggestive of pneumonia. Rarely, patients with lower lobe pneumonia have abdominal or back pain as a presenting symptom. The diagnosis may be more difficult in infants and small children who are unable to give an adequate history. Pneumonia may manifest in infants as a fever associated with irritability, tachypnea, tachycardia, intercostal retractions, nasal flaring, or grunting. Cough may be minimal or absent.

Pneumonia can be divided based on clinical patterns into typical pneumonia caused by pyogenic bacteria, such as S. pneumoniae or H. influenzae, and atypical pneumonia caused by organisms such as Mycoplasma and Chlamydophila species. This division is artificial, and a clear differentiation between these two types of pneumonia on clinical grounds alone is impossible. Certain clinical factors are often said to be suggestive of atypical organisms. Factors studied prospectively and found not to help differentiate atypical pneumonias from those with pyogenic bacterial causes include gradual onset, viral prodrome, absence of rigors, nonproductive cough, lower degree of fever, absence of pleurisy or consolidation, normal leukocyte count, and an ill-defined infiltrate on a chest radiograph. Although it is impossible to determine with a high degree of certainty the specific cause of pneumonia without results of microbiologic or serologic tests, certain clinical factors suggest that a specific pathogen should be considered.

Patients with pneumococcal pneumonia usually appear acutely ill, and the classic presentation is the abrupt onset of a single shaking chill, followed by fever, cough productive of rust-colored sputum, and pleuritic chest pain. Patients with a history of asplenia, sickle cell disease, AIDS, multiple myeloma, or agammaglobulinemia are at increased risk of pneumococcal bacteremia and sepsis with high mortality rates. Adults with chronic lung disease who develop pneumonia caused by H. influenzae typically demonstrate an insidious worsening of baseline cough and sputum production, and bacteremia is rare. K. pneumoniae may cause severe pneumonia in elderly or debilitated patients. Sputum is often described as “currant jelly” because of the necrotizing, hemorrhagic nature of the infection. Abscess formation, empyema, and bacteremia are common with this organism, and mortality is high.

Atypical pneumonia is caused by organisms such as M. pneumoniae, C. pneumoniae, viruses, Legionella species, or rickettsiae such as Coxiella burnetii. Mycoplasmal infection usually begins as a flulike illness with headache, malaise, fever, and nonproductive cough. Skin lesions, including maculopapular, vesicular, urticarial, or erythema multiforme–type rashes, are common, especially in younger patients. Although bullous myringitis is described as a classic finding, it is not specific for mycoplasmal infection and is present in only a few cases. Patients generally do not have a toxic appearance, and most can be treated as outpatients. Although mucopurulent sputum generally indicates the presence of pyogenic bacterial pneumonia or bronchitis, it may also be present with mycoplasmal or viral pneumonia. Viral pneumonia in adults is often preceded by symptoms of upper respiratory infection, such as rhinitis or sore throat. Most C. pneumoniae infections in young adults cause a minor, self-limited upper respiratory illness that is subacute in onset. This organism is also associated with bronchitis, wheezing, sinusitis, and pharyngitis. Development of radiographically evident pneumonia is more common in the elderly. Some patients with Legionella infection have a mild, self-limited atypical pneumonia presentation. Older patients, smokers, and those with chronic disease or immunosuppression are more prone to develop the more acute and severe systemic illness of legionnaires’ disease. Gastrointestinal symptoms, such as diarrhea and abdominal cramping, confusion, and muscle aches are sometimes prominent.

In addition to age, the presence of underlying illness, and presenting symptoms, the setting of acquisition of pneumonia may provide clues to likely causes. CAP that occurs in otherwise healthy individuals is likely to be caused by viruses, Mycoplasma species, or S. pneumoniae. S. aureus, including MRSA, can cause severe pneumonia associated with influenza. Recently hospitalized and long-term care patients may develop pneumonia from agents that are uncommon in CAP, such as Enterobacteriaceae, Pseudomonas aeruginosa, and S. aureus. Healthy patients in an institutional setting, such as a dormitory or military barracks, are likely to have pneumonia caused by Mycoplasma species or viruses.

Patients with underlying lung disease, especially COPD, constitute an important group likely to develop pneumonia. The lower respiratory tract of these patients is commonly colonized with organisms such as S. pneumoniae, H. influenzae, and Moraxella catarrhalis. Cystic fibrosis patients are prone to pneumonia caused by P. aeruginosa or S. aureus. Defective mucociliary clearance in both of these groups makes them highly susceptible to repeated episodes of pneumonia.

Patients with immunosuppression as a result of hematologic malignancy, patients receiving chemotherapy for malignancy, and transplant recipients are prone to pulmonary infections with a wide variety of organisms. In addition to the usual pathogens, these patients may develop pneumonia secondary to viruses such as cytomegalovirus (CMV), varicella, or herpes simplex virus. They are also more likely to develop pneumonia caused by aerobic gram-negative bacilli, Aspergillus and geographic fungi, and P. jiroveci.

Although the use of highly active antiretroviral therapy (HAART) has decreased the incidence of opportunistic infections among HIV-infected patients, individuals who are not under regular care often come to the ED. In addition to P. jiroveci, there is also an increased incidence M. tuberculosis and common bacterial pathogens such as S. pneumoniae. Other less common causes of pneumonia in HIV-infected patients include Mycobacterium avium complex, CMV, aerobic gram-negative bacilli, Cryptococcus neoformans, and Rhodococcus equi. PCP usually has a subacute presentation characterized by nonproductive cough, exertional dyspnea, and weight loss. Tachypnea and tachycardia are usually present. Hypoxemia, hypocapnia, and an increased arterial-alveolar oxygenation gradient are usually present.

The potential for opportunistic pulmonary infection can be predicted by a recent absolute CD4 lymphocyte count less than 200/mm3. This count is often known by patients with recognized HIV infection or may be surmised by a peripheral total lymphocyte count less than 1000/mm3. In patients who do not know their HIV status, the presence of findings such as weight loss, hairy leukoplakia, and oral candidiasis strongly suggests immunosuppression.

Patients in nursing homes or other extended-care facilities are at increased risk for infection with resistant organisms such as P. aeruginosa, K. pneumoniae (including strains producing extended-spectrum β-lactamases), Acinetobacter species, and hospital-associated strains of MRSA. Other risk factors for infection with multidrug-resistant pathogens include (1) hospitalization for 2 or more days in an acute care facility within 90 days of infection; (2) attendance at a hemodialysis clinic; and (3) intravenous antibiotic therapy, chemotherapy, or wound care within 30 days of infection. Any patient with pneumonia in whom any one of these historical features is present, including patients from a nursing home or long-term care facility, is designated as having health care–associated pneumonia (HCAP). HCAP is associated with a greater likelihood of resistant pathogens such as Pseudomonas and MRSA, and mortality is higher than that for CAP.12

Diagnostic Strategies

Although many chest radiographs are obtained unnecessarily for patients with upper respiratory tract infections or bronchitis, it is difficult to identify a set of specific criteria to direct test ordering that is better than the clinical judgment of an experienced physician. A routine chest radiograph for all patients with cough is not necessary. Clinical judgment is more sensitive than suggestive findings (e.g., fever, tachycardia, oxygen desaturation, and an abnormal lung examination). Patients with serious underlying disease, severe sepsis, or shock and those in whom hospitalization is considered should undergo chest radiography. Computed tomography (CT) of the chest is more sensitive than plain radiography for detecting the presence of pulmonary consolidation, although the natural history of CT-positive, plain radiograph–negative pneumonia is not clear.13 Young, healthy adults with a presumptive diagnosis of pneumonia who will be treated as outpatients may have a chest radiograph deferred unless there is a suspicion of immunocompromise or other unusual features of disease. A chest radiograph should be obtained subsequently if there is a poor initial response to treatment. Routine performance of chest radiography for patients with exacerbation of chronic bronchitis or COPD is of low yield and may be limited to patients with other signs of infection or congestive heart failure. Studies of infants with fever show that a routine chest radiograph is of low yield in the absence of other symptoms or signs of lower respiratory tract infection (e.g., abnormal auscultation or elevated respiratory rate).14

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