Pneumonia

Background and Importance

Pneumonia is the leading infectious cause of death worldwide, with over 3.1 million deaths annually. In the United States, there are over 4 million adult cases of community-acquired pneumonia (CAP) annually. The economic burden associated with CAP annually in the United States is over 17 billion dollars. Most cases of CAP are managed in the outpatient setting, and the mortality is low. Pneumonia necessitating hospitalization is associated with a mortality rate as high as 20%. Pneumonia remains challenging because of an expanding spectrum of pathogens including SARS-CoV-2, changing antibiotic resistance patterns, continued introduction of newer antimicrobial agents, and increasing emphasis on cost-effectiveness and outpatient management.

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 the treatment of malignancy, transplantation, or autoimmune disease, resulting in more cases of pneumonia from opportunistic pathogens. Streptococcus pneumoniae is the most frequently identified pathogen and is also associated with increasing antimicrobial resistance. In addition, the threat exists of respiratory infections caused by biologic terrorism or newly recognized pathogens such as COVID-19 that have the potential to spread globally through international travel.

Anatomy and Physiology

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 m ² , about 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, the lower airway tract is a virtually sterile environment.

Pathophysiology

The development of clinical pneumonia requires a defect in host defenses, presence of a particularly virulent organism, or introduction of a large inoculum of organisms. Pneumonia commonly results from microaspiration of upper respiratory pathogens into the sterile lower respiratory tract. If the challenge of invading organisms overwhelms host defenses, microbial proliferation leads to inflammation, an immune response, and clinical pneumonia. If host defenses are weak, a minimal challenge may lead to the development of pneumonia. The challenge with pneumonia is identifying the causative agent rather than making the diagnosis. A careful history, including foreign travel, recent antibiotic use, and exposure to the health care system, such as dialysis or living in a nursing home, can help inform empiric therapy. Empiric therapy should be chosen with activity against the spectrum of likely pathogens based on the patient’s overall clinical presentation.

In the emergency department (ED), it is often difficult to determine the specific cause of pneumonia because routine microbiologic and serologic testing is not available in the time frame of ED evaluation, although rapid polymerase chain reaction (PCR) testing to determine the pathogen is increasingly available. Even in hospitalized patients, the specific microbiologic cause of pneumonia is usually not identified. When identified, S. pneumoniae is the most commonly encountered pathogen in hospitalized patients, with Haemophilus influenzae a distant second. ^, Legionella, Mycoplasma, and Chlamydophila spp., referred to as atypical pathogens, are also prevalent in hospitalized patients. Improved molecular testing has shown that viral pathogens such as rhinoviruses, influenza, parainfluenza, and adenoviruses account for up to one-quarter of etiologies in hospitalized patients. ^,

Among adults requiring intensive care unit (ICU) admission, S. pneumoniae is the most common pathogen, with even higher prevalence among fatal cases. Legionella spp., 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. Atypical organisms, such as Mycoplasma species or viruses, account for a higher proportion of pneumonia in patients with milder illness amenable to outpatient therapy. Atypical organisms can also occur with significant frequency 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 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 capsular polysaccharides of 23 pneumococcal types most commonly associated with pneumonia reduces the likelihood of serious pneumococcal infection. It is recommended for adults at increased risk because of underlying illness or age older than 65 years and others who smoke or have comorbidities such as chronic lung disease. Despite this recommendation, many ED patients have not received the pneumococcal vaccine, and vaccinating eligible patients in this setting seems to be feasible and effective. A 13-valent protein-conjugate pneumococcal vaccine effectively reduces invasive pneumococcal disease and pneumonia in infants and young children. Although underutilized in the adult population, the vaccine has resulted in a marked decrease in the incidence of pneumococcal pneumonia.

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 series. Community-associated strains of methicillin - resistant S. aureus (CA-MRSA) are uncommon in CAP but are more likely to cause severe disease. Often associated with influenza, staphylococcal pneumonias are often necrotizing, with cavitation and pneumatocele formation. Intravenous (IV) 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 40 years. Another important organism in CAP is C. pneumoniae, an intracellular parasite transmitted between humans by respiratory secretions or aerosols. Seroprevalence studies have indicated 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 10% of outpatient CAP cases, although this is underestimated due 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. Legionella is an intracellular organism that lives in aquatic or soil 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 geographic region with a high prevalence in Australia.

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 with oral flora such as Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella spp. 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 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 historically the most common cause of viral pneumonia in adults. Winter influenza outbreaks, usually of influenza type A, may cause up to 40,000 deaths annually in the United States. More than 90% occur in people aged 65 years or older. Updated influenza epidemiology is available from the United States Centers for Disease Control (CDC). Metapneumovirus is a paramyxovirus that is an important cause of viral pneumonia in children and adults. SARS-CoV2 is now the most common viral pneumonia requiring hospitalization. During epidemics, clinicians should suspect a viral agent in patients with hypoxia, fever, and cough.

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 US geographic areas— 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. The clinical presentation varies from an acute or chronic pneumonia to asymptomatic granulomas and hilar adenopathy.

Pneumocystis pneumonia (PCP) occurs in immunocompromised hosts, principally those with acquired immunodeficiency syndrome (AIDS) or malignancy. Pneumocystis jiroveci is one of the most common opportunistic infections leading to a diagnosis of HIV infection (see Chapter 121 ). Patients with pulmonary complaints should be questioned about HIV risk factors, and emergency 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 HIV. Approximately one-third of the world’s population is infected with M. tuberculosis . About 9 million new cases of active disease develop annually, resulting in 1.5 million deaths worldwide. Approximately 2.7 per 100,000 individuals in the United States develop TB each year. Multidrug-resistant strains of M. tuberculosis have been found in increasing numbers, especially among patients with HIV and in immigrants from Southeast Asia.