Community-Acquired Pneumonia (CAP): Dr. Akif Baig

Community-Acquired Pneumonia (CAP) is an acute infection of the pulmonary parenchyma that occurs in individuals outside of hospital or healthcare settings or within 48 hours of admission to a hospital. It is defined by the presence of clinical symptoms such as fever, cough (with or without sputum production), dyspnea, pleuritic chest pain, and abnormal findings on physical examination (such as rales, decreased breath sounds) or radiologic imaging, particularly consolidation on chest X-ray or CT scan.

Etiology of Community-Acquired Pneumonia (CAP)

The etiology of CAP includes a wide variety of bacterial, viral, and atypical pathogens. The specific causative agents often vary depending on patient age, comorbidities, geographic region, and the presence of risk factors like smoking, chronic lung disease, and immunosuppression.

Common Etiological Agents in CAP

Pathogenesis of CAP

The pathogenesis of CAP involves the invasion of lung parenchyma by microbial pathogens, leading to an inflammatory response within the alveoli and interstitial tissues. The mechanisms of disease progression include:

The bacteria may invade the bloodstream, causing bacteremia, septicemia, and sometimes metastatic infection in other organs.

Colonization of the Upper Respiratory Tract:

Pathogens such as Streptococcus pneumoniae colonize the nasopharynx without causing disease in healthy individuals. In patients with impaired host defenses (e.g., smokers, the elderly, or immunocompromised), these pathogens can bypass local barriers.

Aspiration/Inhalation of Pathogens:

The pathogens are inhaled into the lower respiratory tract or aspirated from the oropharyngeal region. Host defense mechanisms, such as mucociliary clearance, are overwhelmed or impaired.

Impaired Host Defense Mechanisms:

The immune system’s first line of defense (alveolar macrophages and mucociliary clearance) is compromised in the elderly, smokers, or those with chronic lung diseases. Viral infections like influenza or SARS-CoV-2 can disrupt epithelial barriers, predisposing patients to bacterial superinfection.

Alveolar Invasion and Inflammation:

Once in the lower respiratory tract, pathogens trigger an inflammatory response. Proinflammatory cytokines (e.g., IL-1, TNF-alpha) are released by alveolar macrophages, leading to neutrophil recruitment. This inflammatory cascade results in alveolar filling with exudate, red blood cells, and fibrin, impairing gas exchange.

Pneumonia Pathophysiology:

The inflammatory response causes alveolar consolidation, reducing lung compliance and causing hypoxemia due to impaired gas exchange.

Risk Factors for Pathogen-Specific CAP

Host-Pathogen Interaction

The balance between pathogen virulence and host defense determines the outcome of CAP. Key host defense mechanisms include:

• Alveolar macrophages: First line of defense against microbial invasion.
• Neutrophils: Recruited to the alveoli to phagocytose and kill pathogens.
• Cytokines and chemokines: These modulate the inflammatory response but can also contribute to tissue damage and alveolar fluid accumulation.

However, in severe cases or with highly virulent pathogens (e.g., Legionella), the host inflammatory response may be exaggerated, leading to widespread alveolar damage, capillary leakage, and severe hypoxemia (acute respiratory distress syndrome, ARDS).

Clinical Stages of Pneumonia (Histopathological Stages)

Key Pathogens and Their Clinical Characteristics

Clinical Features of Community-Acquired Pneumonia (CAP)

The clinical presentation of CAP can vary depending on the causative organism, the patient’s age, and underlying comorbidities. CAP typically presents with the following symptoms:

Typical Symptoms:

• Fever (with or without chills)
• Cough: May be productive or non-productive
  • Productive cough: Sputum may be purulent or blood-tinged (rusty-colored sputum in Streptococcus pneumoniae infection).
• Pleuritic chest pain: Sharp pain that worsens with deep breathing or coughing.
• Dyspnea (shortness of breath): Varies from mild to severe.
• Tachypnea: Increased respiratory rate.

Atypical Symptoms:

• Fatigue, malaise, and weakness: More common in elderly patients.
• Confusion or altered mental status: Particularly in the elderly and severe cases.
• Diarrhea, nausea, vomiting: Can occur in certain pathogens such as Legionella pneumophila.
• Myalgia, arthralgia, and headache: Often associated with viral or atypical pneumonia (Mycoplasma pneumoniae, Chlamydia pneumoniae).

Physical Examination Findings:

• Tachypnea, tachycardia, and hypoxia (in severe cases).
• Crackles (rales) on auscultation: Indicative of alveolar fluid.
• Dullness to percussion: Suggestive of consolidation or pleural effusion.
• Bronchial breath sounds over areas of consolidation.
• Increased tactile fremitus over the affected areas.
• Pleural rub: May be present in cases with pleuritic involvement.

CURB-65 Score: Severity Assessment for CAP

The CURB-65 score is a clinical tool used to assess the severity of CAP and guide decisions regarding hospital admission. Each of the 5 factors below is given 1 point, and the total score helps predict mortality risk.

CURB-65 Components:

CURB-65 Score Interpretation:

Pneumonia Severity Index (PSI): Risk Stratification Tool

The Pneumonia Severity Index (PSI) or PORT score is another widely used tool for determining the severity of CAP and guiding treatment decisions, particularly to assess the need for hospitalization or intensive care. PSI classifies patients into five risk classes based on mortality prediction. It uses a more comprehensive set of criteria compared to CURB-65, which includes demographic, clinical, and laboratory data.

PSI Scoring System:

PSI Risk Classification:

Comparison Between CURB-65 and PSI:

Clinical Application of CURB-65 and PSI:

Both CURB-65 and PSI are useful for predicting the severity and mortality risk of CAP, but they are used in slightly different clinical settings:

PSI is used for more comprehensive risk stratification, especially when considering comorbidities and long-term outcomes, to determine whether outpatient care is feasible.

CURB-65 is preferred in emergency settings for its simplicity and ease of use.

Diagnosis of Community-Acquired Pneumonia (CAP)

According to the latest Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guidelines (2019), the diagnosis of CAP should be based on a combination of clinical, laboratory, and imaging findings.

1. Clinical Diagnosis

The diagnosis of CAP is initially based on clinical features, including:

• History of acute onset respiratory symptoms (e.g., cough, sputum production, dyspnea, pleuritic chest pain, fever, chills).
• Physical examination findings suggestive of pneumonia (e.g., crackles, diminished breath sounds, dullness to percussion).
• Presence of risk factors for CAP (e.g., smoking, advanced age, chronic lung disease, immunocompromised state).

However, clinical symptoms alone are not sufficient for a definitive diagnosis, as they can overlap with other respiratory conditions such as bronchitis or asthma. Therefore, clinical diagnosis should be supported by imaging and laboratory investigations.

2. Laboratory Investigations

To confirm the presence of infection and assess the severity of disease, the following tests are recommended:

• Complete blood count (CBC): Elevated white blood cell count (leukocytosis) with a left shift (increased neutrophils) is common.
• C-reactive protein (CRP) or procalcitonin: These biomarkers may help differentiate bacterial from viral pneumonia.
• Blood cultures: Recommended in patients with severe CAP or those being admitted to the hospital, especially to detect bacteremia caused by Streptococcus pneumoniae or Staphylococcus aureus.
• Sputum culture and Gram stain: Especially useful in hospitalized patients to identify the causative pathogen.
• Urinary antigen tests: For rapid detection of Streptococcus pneumoniae and Legionella pneumophila in severe CAP cases.
• Nasal or throat swabs: For PCR testing to identify respiratory viruses, especially during influenza season or in cases of suspected viral pneumonia (e.g., SARS-CoV-2, RSV, or influenza).

3. Imaging in CAP Diagnosis

Chest imaging is essential for confirming the diagnosis of CAP. The latest IDSA/ATS guidelines emphasize the importance of chest radiography or, in some cases, chest CT for establishing the presence of pneumonia.

Chest Radiography (X-ray)

• Standard chest X-ray remains the cornerstone of CAP diagnosis.
• It should be obtained in all patients with suspected CAP to confirm the presence of pulmonary infiltrates (e.g., lobar consolidation, interstitial infiltrates, or cavitation).
• Findings: The presence of new or progressive infiltrates supports the diagnosis of pneumonia.Common radiographic patterns include:
  • Lobar consolidation: Common in bacterial pneumonia, especially Streptococcus pneumoniae.
  • Interstitial infiltrates: More typical of viral or atypical pathogens (e.g., Mycoplasma pneumoniae, Legionella).
  • Cavitation: Suggests necrotizing pneumonia, often caused by Staphylococcus aureus or gram-negative pathogens.
  • Pleural effusion: Seen in more severe cases, can indicate complicated pneumonia.
  Note: A normal chest X-ray does not completely rule out pneumonia, particularly in early stages, immunocompromised patients, or dehydrated individuals. A repeat X-ray may be needed if clinical suspicion remains high.

Chest Computed Tomography (CT)

• Chest CT is not routinely recommended for all patients but can be helpful in cases where:
  • The diagnosis is uncertain (e.g., equivocal chest X-ray findings).
  • There is suspicion of complications (e.g., abscess, empyema, or necrotizing pneumonia).
  • Atypical pathogens or unusual presentations are suspected.
  CT findings include:
  • More detailed visualization of lung parenchyma, useful in identifying small or early infiltrates.
  • Detection of cavitation or lymphadenopathy.

Ultrasound

• Lung ultrasound may be used in certain settings, especially in critically ill patients or those who cannot undergo a chest X-ray. It is helpful in identifying consolidations and pleural effusions, although it is less commonly used compared to chest X-ray or CT in the initial evaluation of CAP.

Summary of Diagnostic Imaging

IDSA/ATS 2019 Guidelines on Imaging for CAP

The 2019 guidelines from IDSA/ATS recommend the use of chest radiography for all patients with suspected CAP to confirm the diagnosis and rule out other potential causes of respiratory symptoms. Chest CT is reserved for complicated or unclear cases, while lung ultrasound may be used in critically ill patients where X-ray is not feasible.

Treatment of Community-Acquired Pneumonia (CAP)

The treatment of CAP is guided by the severity of the disease, the patient’s age, comorbid conditions, and local pathogen resistance patterns. The 2019 IDSA/ATS Guidelines recommend stratifying treatment into outpatient, inpatient (non-ICU), and inpatient (ICU) settings, based on severity scores like CURB-65 or Pneumonia Severity Index (PSI).

1. Outpatient Management

Outpatient treatment is appropriate for patients with mild CAP who have low severity scores (e.g., CURB-65 score of 0 or 1, or PSI class I or II).

Empiric Antibiotic Therapy (Outpatient)

• Previously healthy patients with no comorbidities or recent antibiotic use:
  • First-line:
    • Amoxicillin: 1 g PO three times daily (high-dose to cover resistant S. pneumoniae).
    • Doxycycline: 100 mg PO twice daily (alternative if penicillin allergy or suspected atypical pathogens).
  • Alternative for atypical pathogens (e.g., Mycoplasma pneumoniae, Chlamydia pneumoniae):
    • Azithromycin: 500 mg PO on day 1, then 250 mg PO daily on days 2–5.
    • Clarithromycin: 500 mg PO twice daily for 5–7 days (note increased resistance in some areas).
• Patients with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy) or recent antibiotic use:
  • First-line (combination therapy):
    • Amoxicillin-clavulanate: 875 mg/125 mg PO twice daily or 500 mg/125 mg PO three times daily or
    • Cefuroxime: 500 mg PO twice daily, PLUS
    • Azithromycin: 500 mg PO on day 1, then 250 mg PO daily on days 2–5, or
    • Doxycycline: 100 mg PO twice daily.
  • Alternative monotherapy:
    • Levofloxacin: 750 mg PO daily for 5 days (covers both typical and atypical organisms).
    • Moxifloxacin: 400 mg PO daily for 5 days.

2. Inpatient Management (Non-ICU)

Patients with moderate CAP (e.g., CURB-65 score of 2, or PSI class III or IV) who do not require ICU admission should be hospitalized.

Empiric Antibiotic Therapy (Inpatient, Non-ICU)

• Combination Therapy (Preferred):
  • Beta-lactam + macrolide:
    • Ceftriaxone: 1–2 g IV once daily, PLUS
    • Azithromycin: 500 mg IV/PO once daily.
  Alternative Beta-lactams:
  • Cefotaxime: 1–2 g IV every 8 hours, OR
  • Ampicillin-sulbactam: 1.5–3 g IV every 6 hours.
• Monotherapy (for penicillin-allergic patients):
  • Levofloxacin: 750 mg IV/PO once daily, or
  • Moxifloxacin: 400 mg IV/PO once daily.

Considerations for Specific Pathogens:

• Legionella pneumonia: Empiric coverage with macrolide (azithromycin) or fluoroquinolone (levofloxacin).
• MRSA suspected (e.g., recent influenza or risk factors for MRSA):
  • Add Vancomycin: 15–20 mg/kg IV every 8–12 hours (target trough: 15–20 mg/L) or
  • Linezolid: 600 mg IV/PO twice daily.
• Pseudomonas aeruginosa suspected (e.g., structural lung disease):
  • Use Piperacillin-tazobactam: 4.5 g IV every 6 hours, or
  • Cefepime: 2 g IV every 8 hours, PLUS
  • Levofloxacin: 750 mg IV daily or an aminoglycoside (e.g., tobramycin).

3. Inpatient Management (ICU)

Patients with severe CAP (e.g., CURB-65 score ≥ 3, or PSI class V) who require intensive care due to respiratory failure, sepsis, or shock need aggressive treatment.

Empiric Antibiotic Therapy (Inpatient, ICU)

• Combination Therapy (Preferred):
  • Beta-lactam + macrolide:
    • Ceftriaxone: 1–2 g IV once daily, or
    • Cefotaxime: 1–2 g IV every 8 hours, or
    • Ampicillin-sulbactam: 3 g IV every 6 hours, PLUS
    • Azithromycin: 500 mg IV once daily.
  Alternative Combination:
  • Beta-lactam + fluoroquinolone:
    • Ceftriaxone or Cefotaxime (as above), PLUS
    • Levofloxacin: 750 mg IV once daily, or
    • Moxifloxacin: 400 mg IV once daily.

Special Considerations (ICU):

• MRSA coverage: Add Vancomycin or Linezolid if Staphylococcus aureus is suspected.
• Pseudomonas coverage: In patients at risk for Pseudomonas infection, use:
  • Piperacillin-tazobactam: 4.5 g IV every 6 hours, or
  • Cefepime: 2 g IV every 8 hours, PLUS
  • Levofloxacin: 750 mg IV daily or an aminoglycoside.

4. Duration of Therapy

• The duration of antibiotic therapy depends on the clinical response:
  • Outpatients: 5 days of therapy is typically sufficient if the patient shows clinical improvement (afebrile for 48–72 hours and stable vitals).
  • Inpatients (non-ICU): 5–7 days of therapy, tailored to clinical response.
  • ICU patients: 7–10 days of therapy is generally recommended, especially if the clinical course is complicated by bacteremia or other factors.
  • Atypical pathogens (e.g., Legionella, Mycoplasma) may require extended therapy (up to 10–14 days).

Adjunctive Therapy

• Corticosteroids: Not routinely recommended in non-severe CAP but may be considered in select cases of severe CAP or refractory septic shock.
• Oxygen therapy: Supplemental oxygen should be provided as needed to maintain oxygen saturation ≥92%.
• Mechanical ventilation: In cases of respiratory failure, invasive or non-invasive mechanical ventilation may be required.

Monitoring and Follow-up

• Clinical response should be assessed within 48–72 hours of initiating therapy. Failure to improve may prompt further investigation (e.g., repeat cultures, chest imaging) and consideration of complications (e.g., pleural effusion, abscess).
• Routine follow-up chest X-rays are not required in uncomplicated cases but may be performed after several weeks in patients with slow clinical recovery or suspicion of underlying malignancy.

Summary of CAP Treatment Based on 2019 IDSA/ATS Guidelines

Key Notes:

• Duration: Antibiotic therapy is typically 5 days for outpatients, but can be extended to 7–10 days for hospitalized patients based on clinical response.
• Special Pathogen Considerations:
  • For suspected Legionella, a macrolide or fluoroquinolone is preferred.
  • In cases of MRSA, vancomycin or linezolid should be added.
  • Pseudomonas coverage is required in patients with structural lung disease or other risk factors.

References:

• Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7)
• BMJ Best Practice. Community-Acquired Pneumonia. Available from: https://bestpractice.bmj.com/topics/en-gb/3000108
• 21st edition of Harrison textbook of Internal Medicine