Community-Acquired Pneumonia

Etiology

Many pathogens cause community-acquired pneumonia, including bacteria, viruses, and fungi.[6] Common bacterial pathogens can be classified as:

• Gram-positive agents such as Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, and other streptococci 
• Gram-negative agents such as Haemophilus influenzae, Moraxella catarrhalis, and Enterobacteriaceae
• Atypical agents such as Legionella, Mycoplasma, Chlamydia pneumoniae, and Chlamydia psittaci [7] 

Among viruses, rhinovirus, influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other respiratory viruses (parainfluenza, respiratory syncytial virus, human metapneumovirus, etc) have become increasingly detected as pathogens based on molecular detection methods. Worldwide, S pneumoniae and H influenzae are still the leading causes of acute bacterial pneumonia (see Image. Mycobacterium Avium-Intracellulare Pneumonia). The most recent population-based active surveillance in the United States identified that human rhinovirus, influenza virus, and S pneumoniae were the most common pathogens.[8] 

Epidemiology

The estimated worldwide incidence of community-acquired pneumonia varies between 1.5 to 14 cases per 1000 person-years and is affected by geography, season, and population characteristics.[5] In the US the annual incidence is 24.8 cases per 10,000 adults, with higher rates as age increases. Pneumonia is the eighth leading cause of death and first among infectious causes of death. The mortality rate is as high as 23% for patients admitted to the intensive care unit for severe pneumonia.

All patients with comorbid illness are considered at risk for pneumonia, but specific risk factors exist for particular pathogens. Drug-resistant pneumococci are more likely in:

• Those older than 65
• Children in daycare centers
• Those who have taken beta-lactam antibiotics in the previous 90 days
• Individuals with alcohol use disorder, chronic medical conditions, and immune suppression

Pseudomonas pneumonia is more likely in those with:

• Bronchiectasis
• Malnutrition
• Corticosteroid therapy
• Antibiotic intake for greater than 7 days in the preceding month

Other etiological clues from geographic regions include the following: 

• Coccidioidomycosis in the Southwestern US
• Blastomycosis or histoplasmosis in the states of the Ohio River valley bird exposures for Chlamydia psittaci
• Contact with flea-infested or infected rodents or rabbits during outside activities such as lawn mowing in the Northeast US (Martha's Vineyard, Cape Cod, etc) for tularemia pneumonia 

Pathophysiology

Pathogens initially colonize the pharynx, followed by micro-aspiration, which is the mechanism of entry into the lower respiratory tract. Once there, the pathogen induces the host's pulmonary defense. If there is a defect in the host's defense or it is overcome by high inoculum or virulence of the pathogen, then pneumonia will result. Pathogens may also spread through the hematogenous route and macro-aspiration.

History and Physical

Common symptoms of pneumonia include fever, chills, cough productive of purulent sputum, dyspnea, pleuritic chest pain, and weight loss. Patients with alcohol use disorder and those who are immune-compromised may have an absence of fever and less evident or systemic symptoms such as weakness, lethargy, altered mental status, dyspepsia, or other upper gastrointestinal symptoms. The presence of some symptoms may provide etiological clues. For example, diarrhea, headache, and confusion (related to hyponatremia) can indicate Legionella infection; otitis media, Stevens-Johnson syndrome, or anemia with jaundice (hemolytic anemia) may indicate Mycoplasma infection. Pneumonia can provoke acute decompensation of an underlying chronic illness, such as congestive heart failure, and can confound the initial presentation of pneumonia and result in delays in diagnosis and treatment.

Evaluation

Initial workup for pneumonia will include imaging and blood work (see Images. Lung Abscess, Computed Tomography Scan and Bilateral Pneumonia, Computed Tomography Scan and Lung Pneumonia with Fibrosis). A chest x-ray will be needed to identify an infiltrate or effusion, which, if present, will improve diagnostic accuracy (see Image. Healthy Lung and Q Fever Pneumatic Lung, Chest X-ray). Bloodwork should include a complete blood count with differentials; serum electrolytes with renal and liver function tests help confirm evidence of inflammation and assess severity. Influenza testing is recommended during the winter season. Testing for respiratory viruses on nasopharyngeal swabs by molecular methods can be considered if available.

Tools such as CURB 65 (confusion, urea greater than or equal to 20 mg/dL, respiratory rate greater than or equal to 30/min, blood pressure systolic less than 90 mm Hg or diastolic less than 60 mm Hg), and Pneumonia Severity Index for severity assessment may assist in determining the treatment setting, such as outpatient versus inpatient. Still, accuracy is limited when used alone or without practical clinical judgment.

In hospitalized patients, blood and sputum cultures should be collected, preferably before the institution of antimicrobial therapy, but without delay in treatment. If cultures are negative, urine collection and testing for legionella and pneumococcal antigens must be considered as they aid in diagnosis. In the presence of confounding comorbidities, such as congestive heart failure, serum procalcitonin levels can be used as a biomarker to initiate and guide antimicrobial therapy. Serology for tularemia, endemic mycoses, or C psittaci can be evaluated in the presence of epidemiologic clues.[9][10][11]

Treatment / Management

Monotherapy with a macrolide (erythromycin, azithromycin, or clarithromycin) or doxycycline is recommended in the outpatient setting. In the presence of comorbid illness (chronic heart disease excluding hypertension); chronic lung disease (chronic obstructive pulmonary disease and asthma); chronic liver disease; chronic alcohol use disorder; diabetes mellitus; smoking; splenectomy; human immunodeficiency virus (or other immunosuppression); a respiratory fluoroquinolone (high-dose levofloxacin, moxifloxacin, gemifloxacin); a combination of oral beta-lactam (high dose amoxicillin or amoxicillin-clavulanate, cefuroxime, cefpodoxime); and macrolide is recommended.[11][12][13][14](B2)

Inpatient management is recommended for patients with a CURB 65 score greater than or equal to 2. A respiratory fluoroquinolone monotherapy or combination therapy with beta-lactam (cefotaxime, ceftriaxone, ampicillin-sulbactam, or ertapenem) and macrolide are recommended options for non-intensive care settings.

Admission to the intensive care unit must be considered in patients with 3 or more signs of early deterioration. These include respiratory rate greater than 30, PaO₂/FiO₂ less than or equal to 250, multilobar infiltrates, encephalopathy, thrombocytopenia, hypothermia, leucopenia, and hypotension. Combination therapy with a beta-lactam and either a macrolide or a respiratory fluoroquinolone is recommended. In patients with suspected aspiration, ampicillin-sulbactam or ertapenem can be used. Monotherapy is not recommended.

If risk factors for Pseudomonas are present, then antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, ceftazidime, meropenem, imipenem) along with either an antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or a combination of aminoglycoside and azithromycin are recommended. Vancomycin or linezolid should be added if community-acquired methicillin-resistant S aureus is a consideration. 

The recommended duration of therapy is 5 to 7 days in patients with a favorable clinical response, such as the absence of fever for more than 48 to 72 hours, not requiring supplemental oxygen, and resolution of tachycardia, tachypnea, or hypotension. Prolongation of therapy is indicated in patients with a delayed response, specific bacterial pathogens such as Pseudomonas (14-21 days) or S aureus (7-21 days), or Legionella pneumonia (14 days), and for complications such as empyema, lung abscess, or necrotizing pneumonia. Chest tube placement will be needed to drain an empyema, and in cases with multiple loculations, a surgical decortication may be needed. A 14-day therapy with macrolide or doxycycline will treat tularemia pneumonia or psittacosis, and itraconazole is the drug of choice for pneumonia caused by coccidioidomycosis or histoplasmosis.

A 5-day therapy with oseltamivir is recommended for all patients who test positive for the influenza virus and present within 48 hours of symptom onset; there is no benefit to oseltamivir if started beyond 48 hours after symptom onset. Still, any hospitalized patients with influenza must be treated with this agent regardless of the presentation time from the beginning of the illness. 

Intravenous glucocorticoids can be considered adjunctive therapy in critically ill patients with severe community-acquired pneumonia without risk factors for adverse outcomes from using steroids (eg, influenza infection). They are associated with reductions in short-term mortality and duration of intensive care days.[15][16][17][18](A1)

Differential Diagnosis

Differential diagnoses for community-acquired pneumonia include:

• Acute bronchitis
• Acute exacerbation of chronic bronchitis
• Aspiration pneumonitis
• Congestive heart failure and pulmonary edema
• Pulmonary fibrosis
• Myocardial infarction
• Systemic lupus erythematosus pneumonitis
• Pulmonary drug hypersensitivity reactions (nitrofurantoin, daptomycin)
• Drug-induced pulmonary disease (bleomycin)
• Sarcoidosis
• Cryptogenic organizing pneumonia
• Pulmonary embolus
• Pulmonary infarction
• Bronchogenic carcinomas
• Granulomatosis with polyangiitis (Wegener granulomatosis)
• Lymphoma
• Tracheobronchitis
• Radiation pneumonitis