Pneumonia

Pneumonia is a respiratory infection characterized by inflammation of the alveolar space and/or the interstitial tissue of the lungs. In industrialized nations, it is the leading infectious cause of death. Pneumonia is most commonly transmitted via aspiration of airborne pathogens (primarily bacteria, but also viruses and fungi) but may also result from the aspiration of stomach contents. The most likely causal pathogens can be narrowed down based on patient age, immune status, and where the infection was acquired (community-acquired or hospital-acquired). Pneumonia is classified based on clinical features as either typical and atypical; each type has its own spectrum of commonly associated pathogens. Typical pneumonia manifests with sudden onset of malaise, fever, and a productive cough. On auscultation, crackles and bronchial breath sounds are audible. Atypical pneumonia manifests with gradual onset of unproductive cough, dyspnea, and extrapulmonary manifestations. Auscultation is usually unremarkable. Some patients may present with elements of both types. Diagnostics include blood tests for inflammatory parameters and pathogen detection in blood, urine, or sputum samples. Chest x-ray in cases of typical pneumonia shows opacity restricted to one lobe, while x-ray in atypical pneumonia may show diffuse, often subtle infiltrates. Together with the characteristic clinical features, newly developed pulmonary infiltrate on chest x-ray confirms the diagnosis. Management consists of empiric antibiotic treatment and supportive measures (e.g., oxygen administration, antipyretics).

Pathogens

Risk factors

• Old age and immobility of any cause
• Chronic diseases
  • Pre-existing cardiopulmonary conditions; (e.g., bronchial asthma, COPD, heart failure)
  • Acquired or congenital abnormalities of the airways (e.g., bronchiectasis, space-occupying lesions, cystic fibrosis)
• Immunosuppression (e.g., HIV infection, diabetes mellitus, cytostatic therapy, alcoholism, immunosuppressive therapy, malnutrition)
• Smoking
• Impaired airway protection → aspiration
  • Alteration in consciousness (e.g., stroke, seizure, anesthesia, drugs, alcohol)
  • Dysphagia
• Environmental factors
  • Crowded living conditions (e.g., prisons, homeless shelters)
  • Toxins (e.g., solvents, gasoline)
• Cryptogenic organizing pneumonia
  • Specific medications; (e.g., amiodarone, bleomycin)
  • Chronic inflammatory disorders (e.g., rheumatoid arthritis)

References:^[1][2][3]

Pneumonia can be classified according to etiology, location acquired, clinical features, and the area of the lung affected by the pathology.

• Etiology
  • Primary pneumonia: no apparent pre-existing conditions that may predispose to pneumonia
  • Secondary pneumonia
    • Bronchial asthma, COPD, heart failure, cystic fibrosis
    • Viral upper respiratory tract infections with bacterial superinfection
    • Anatomical abnormalities such as tubercular caverns, bronchial tumors, or stenosis (postobstructive pneumonia)
    • Aspiration pneumonia
• Location acquired
  • Community-acquired pneumonia (CAP): pneumonia that is acquired outside of a healthcare establishment
  • Hospital-acquired pneumonia (HAP): nosocomial pneumonia, with onset > 48 hours after admission
    • Ventilator-associated pneumonia (VAP): pneumonia occurring in patients who are on mechanical ventilation breathing machines in hospitals (typically in the intensive care unit)
  • Healthcare-associated pneumonia (HCAP): pneumonia that is acquired in healthcare facilities (e.g., hospital, nursing homes, hemodialysis centers, and outpatient clinics); this terminology is no longer recommended but is included for historical purposes. ^[4][5]
• Clinical features (see “Clinical features”)
  • Typical pneumonia
    • Pneumonia featuring classic symptoms; typical findings on auscultation and percussion
    • Manifests as lobar pneumonia or bronchopneumonia
  • Atypical pneumonia
    • Pneumonia with less distinct classical symptoms and often unremarkable findings on auscultation and percussion
    • Manifests as interstitial pneumonia
• Area of lung affected by the pathology (see “Pathophysiology”)
  • Lobar pneumonia: pneumonia affecting one lobe of a lung
    • Multilobar pneumonia refers to the involvement of multiple lobes in a single lung or both lungs.
    • Panlobar pneumonia involves all the lobes of a single lung.
  • Bronchial pneumonia: pneumonia affecting the tissue around the bronchi and/or bronchioles
  • Interstitial pneumonia: pneumonia affecting the tissue between the alveoli
  • Cryptogenic organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia): a noninfectious pneumonia of unknown etiology characterized by the involvement of the bronchioles, alveoli, and surrounding tissue

References:^[6][7]

Routes of infection

• Most common: microaspiration (droplet infection) of airborne pathogens or oropharyngeal secretions
• Aspiration of gastric acid (aspiration pneumonitis) , food, or liquids
• Hematogenous dissemination (rare)

Pathogenesis

1. Failure of protective pulmonary mechanisms (cough reflex, mucociliary clearance ; , alveolar macrophages )
2. Pathogen infiltrates pulmonary parenchyma → interstitial and alveolar inflammation
3. Impaired alveolar ventilation → ventilation/perfusion (V/Q) mismatch with intrapulmonary shunting (right to left)
4. Hypoxia due to increased alveolar-arterial oxygen gradient
   • Hypoxia is worsened when the affected lung is in the dependent position, as perfusion to the dependent lung is better compared to the nondependent lung.
   • In the case of a large unilateral pulmonary abscess, it may be helpful to position the patient so that the affected lung is in the dependent position in order to prevent pus from filling the unaffected lung.

Pattern of involvement

• Lobar pneumonia
  • Classic (typical) pneumonia of an entire lobe; primarily caused by pneumococci
  • Characterized by inflammatory intra-alveolar exudate, resulting in consolidation
  • Can involve the entire lobe or the whole lung

• Bronchopneumonia: mostly commonly a descending infection that affects the bronchioles and adjacent alveoli; usually involves the lower lobes or right middle lobe; manifests as typical pneumonia ^[8]
  • Primarily caused by pneumococci and/or other streptococci
  • Necrotizing bronchopneumonia and pneumatocele are caused by Staphylococcus aureus and are often preceded by an influenza infection.
  • Characterized by acute inflammatory infiltrates that fill the bronchioles and the adjacent alveoli (patchy distribution)
  • Usually affects ≥ 1 lobe
• Interstitial pneumonia: interstitial inflammation, typically caused by mycoplasma and viral infections; manifests as atypical pneumonia
  • Characterized by a diffuse patchy inflammation that mainly involves the alveolar interstitial cells
  • Bilateral multifocal opacities are classically found on chest x-ray.
  • Often has an indolent course (walking pneumonia)
• Miliary pneumonia: multiple small infiltrations caused by hematogenous dissemination (e.g., of tuberculosis)
• Cryptogenic organizing pneumonia: characterized by inflammation of the bronchioles and surrounding structures

References:^[9]

Typical pneumonia

Typical pneumonia is characterized by a sudden onset of symptoms caused by lobar infiltration.

• Severe malaise
• High fever and chills
• Productive cough with purulent sputum (yellow-greenish)
  • Crackles and decreased bronchial breath sounds on auscultation
  • Enhanced bronchophony, egophony, and tactile fremitus
  • Dullness on percussion
• Tachypnea and dyspnea (nasal flaring, thoracic retractions)
• Pleuritic chest pain when breathing, often accompanying pleural effusion
• Pain that radiates to the abdomen and epigastric region (particularly in children)

Suspect bacterial pneumonia in immunocompromised patients with acute high fever and pleural effusion!

Atypical pneumonia

Atypical pneumonia typically has an indolent course (slow onset) and commonly manifests with extrapulmonary symptoms.

• Nonproductive, dry cough
• Dyspnea
• Auscultation often unremarkable
• Common extrapulmonary features include fatigue, headaches, sore throat, myalgias, and malaise.

As it is not always possible to clearly distinguish between typical and atypical pneumonia, this classification does not have a major impact on patient management.

References:^{[10][11][8][12][13]}

Pneumonia is a clinical diagnosis based on history, physical examination, laboratory findings, and CXR findings. Consider microbiological studies and advanced diagnostics based on patient history, comorbidities, severity, and entity of pneumonia. ^[14]

Laboratory studies

Routine

• CBC, inflammatory markers: ↑ CRP, ↑ ESR, leukocytosis
• ↑ Serum procalcitonin (PCT): Procalcitonin is an acute phase reactant that can help to diagnose bacterial lower respiratory tract infections. ^[5]
  • PCT can be used to guide antibiotic treatment but should not be used to decide if antibiotic therapy is necessary on its own. ^[5][15][16]
  • PCT levels ≥ 0.25 mcg/L correlate with an increased probability of a bacterial infection.
  • Low PCT level after 2–3 days of antibiotic therapy can help facilitate the decision to discontinue antibiotics. ^[16]
    • Decrease of PCT to ≤ 80% of peak level
    • Decrease of PCT to < 0.25 mcg/L
• ABG: ↓ P_aO₂ ^[14]
• BMP, LFTs

Microbiological studies

Imaging

• Chest x-ray (posteroanterior and lateral)
  • Indications: all patients suspected of having pneumonia
  • Findings may include:
    • Lobar pneumonia
      • Opacity of one or more pulmonary lobes
      • Presence of air bronchograms : appearance of translucent bronchi inside opaque areas of alveolar consolidation
    • Bronchopneumonia
      • Poorly defined patchy infiltrates scattered throughout the lungs
      • Presence of air bronchograms
    • Atypical or interstitial pneumonia
      • Diffuse reticular opacity
      • Absent (or minimal) consolidation
    • Parapneumonic effusion

A new pulmonary infiltrate on chest x-ray in a patient with classic symptoms of pneumonia confirms the diagnosis.

Typical pneumonia usually appears as lobar pneumonia on x-ray, while atypical pneumonia tends to appear as interstitial pneumonia. However, the underlying pathogen cannot be conclusively identified based on imaging results alone.

• Chest CT without contrast
  • Indications
    • Inconclusive chest x-ray
    • Recurrent pneumonia
    • Poor response to treatment
  • Advantages: more reliable evaluation of circumscribed opacities, pleural empyema, or sites of consolidation
  • Findings may include: ^[17]
    • Localized areas of consolidation (hyperdense)
    • Air bronchograms
    • Ground-glass opacities
    • Pleural effusion/empyema: hyperdense fluid collection, split pleura sign
    • Nodules: large , peribronchial , disseminated

Advanced diagnostics

• Bronchoscopy
  • Indications
    • Suspected mass (e.g., recurrent pneumonia)
    • Need for pathohistological diagnosis (e.g., biopsy of a central mass discovered on CT)
    • Inconclusive results on CT
    • Poor response to treatment
• Diagnostic thoracentesis
  • Indications: consider if pleural effusion > 10 mm is present to evaluate for pleural empyema ^[18][14]
  • Findings: see “Diagnostics” and parapneumonic effusion in pleural effusion.
  • Consider therapeutic thoracentesis in large effusions (≥ half of the hemithorax) or if the effusion is suspected of causing dyspnea ^[18]
  • Consider tube thoracostomy if pleural empyema (e.g., echogenic debris on lung ultrasound) or complicated effusion (e.g.,pH < 7.20, glucose < 60 mg/dL, LDH above three times the upper limit of serum LDH, positive culture) is suspected ^[18]

Criteria for hospitalization

Every patient should be assessed individually and clinical judgment is the most important factor. The pneumonia severity index (PSI) and the CURB-65 score are tools that can help to determine whether to admit a patient.

• CURB-65 score ^[19]
  • Confusion (disorientation, impaired consciousness)
  • Serum Urea > 7 mmol/L (20 mg/dL)
  • Respiratory rate ≥ 30/min
  • Blood pressure: systolic BP ≤ 90 mm Hg or diastolic BP ≤ 60 mm Hg
  • Age ≥ 65 years
  • Interpretation
    • Each finding is assigned 1 point.
    • CURB-65 score 0 or 1: The patient may be treated as an outpatient.
    • CURB-65 score ≥ 2: Hospitalization is indicated.
    • CURB-65 score ≥ 3: Consider ICU level of care.
  • CRB-65 score (if serum urea is not known or unavailable)
    • CRB-65 score of 0: The patient may be treated as an outpatient.
    • CRB-65 score of ≥ 1: Hospitalization is recommended.
• Pneumonia severity index (PSI/PORT score) ^[20]
  • Patients are assigned to one of five risk classes based on a more complex point system than in CURB-65.
  • Points are distributed based on patient age, comorbidities, and lab results.

The CURB-65 score and PSI are tools for evaluating the risk of mortality. They have not been validated for determining the necessity for ICU admission.

Criteria for ICU admission

• The decision of whether to admit a patient to the ICU should be based on clinical judgment.
• The IDSA/ATS criteria for severe CAP can be used to help triage patients with CAP and guide empiric antibiotic treatment decisions. ^[5]

Empiric antibiotic therapy for community-acquired pneumonia ^[5][21]

Outpatient

• Duration of treatment
  • 5 days of therapy is usually sufficient for CAP that is treated in the outpatient setting.
  • Any patient being treated in a primary care setting should be re-examined after 48–72 hours to evaluate the efficacy of the prescribed antibiotic.
• Additional considerations: Knowing local resistance patterns of S. pneumoniae to macrolides is critical when deciding on an empiric antibiotic regimen.

Inpatient

• Duration of therapy
  • 5–7 days is usually sufficient.
  • Consider longer courses in patients with one of the following:
    • Patient not responding to treatment
    • Suspected or concern for MRSA or P. aeruginosa infection
    • Concurrent meningitis
    • Unusual pathogens (e.g., Burkholderia pseudomallei, fungal infection)
• Additional considerations
  • If aztreonam is used instead of a β-lactam antibiotic (e.g., for penicillin allergy), the addition of MSSA coverage (e.g., a fluoroquinolone) is necessary.
  • Anaerobic coverage is not routinely recommended for suspected aspiration pneumonia (unless lung abscess or empyema is suspected). ^[5]
  • Corticosteroids are not routinely recommended as adjunct therapy. ^[5]

If aztreonam is used as an alternative to other β-lactam antibiotics, additional coverage for MSSA must be included (e.g., a fluoroquinolone).

Empiric antibiotic therapy for hospital-acquired pneumonia ^[4]

• Duration of treatment
  • Empiric antibiotic therapy should be narrowed and/or de-escalated as soon as feasible.
  • Seven days of therapy are usually sufficient. ^[4]
• Additional considerations: Resistance patterns can vary widely; local antibiograms should be considered when starting empiric treatment.

Patients with structural lung disease and/or at high risk for mortality should receive double antipseudomonal coverage!

Empiric antibiotic therapy for ventilator-associated pneumonia ^[4]

• Recommended combination therapy
  • An antipneumococcal, antipseudomonal β-lactam
    • Aztreonam
    • Imipenem
    • Meropenem
    • Ceftazidime
    • Cefepime
    • Piperacillin-tazobactam
  • PLUS one of the following antibiotics with MRSA activity:
    • Vancomycin
    • Linezolid
  • PLUS one of the following:
    • A fluoroquinolone
      • Levofloxacin
      • Ciprofloxacin
    • An aminoglycoside
      • Amikacin
      • Gentamicin
      • Tobramycin
    • A polymyxin
      • Colistin
      • Polymyxin B
• Duration of treatment: Seven days of therapy are usually sufficient. ^[4]
• Additional considerations:
  • Risk factors for multi-drug resistant organisms (e.g., presence of structural lung disease, recent IV antibiotic therapy, local resistance patterns) should be considered when deciding on an empiric regimen
  • Empiric antibiotic therapy for ventilator-associated tracheobronchitis is not routinely recommended. ^[4]

Supportive therapy

• Sufficient rest (not absolute bed rest) and physical therapy
• Hydration with PO fluids or IV fluids (see IV fluids)
• Treat hypoxemia.
  • Supplemental oxygen as needed for hypoxia
  • See also airway management and mechanical ventilation.
• Incentive spirometer
• Antipyretics, analgesics as needed (e.g., acetaminophen )
• Expectorants and mucolytics ^[22]
• Antitussives (e.g., codeine )

• Calculate the CURB-65 score and/or PSI/PORT score to identify patients who would benefit from admission.
• Assess severity of CAP with the IDSA/ATS criteria for severe CAP.
• Order microbiological workup as indicated by patient severity and risk factors.
• Start empiric antibiotic therapy based on patient risk factors and need for hospitalization (see treatment of pneumonia). ^[5][14][4]
• Evaluate and treat sepsis if present (see sepsis).
• Administer supplemental oxygen if patient is hypoxemic.
• Consider advanced diagnostic evaluation. ^[21]
• Provider supportive care (e.g., antipyretic therapy, antitussives, IV fluids).
• Continuous pulse oximetry
• Trend inflammatory markers, procalcitonin.
• Narrow antibiotic therapy as soon as feasible.

• Mycoplasma pneumonia ^[12][13]
  • Epidemiology
    • One of the most common causes of atypical pneumonia
    • More common in young children
    • Outbreaks may occur in schools, colleges, prisons, and military facilities.
  • Clinical features
    • See atypical pneumonia.
    • Generalized papular rash; erythema multiforme ^[23]
  • Diagnostics
    • Subclinical hemolytic anemia: associated with elevated cold agglutinin titers (IgM)
    • Interstitial pneumonia, often with reticulonodular pattern on chest x-ray
  • Treatment: macrolides, doxycycline, and fluoroquinolones
• Legionnaires' disease
• Pneumocystis pneumonia
• Tuberculosis
• Primary influenza pneumonia
• Various viral infections (e.g., respiratory-syncytial-virus, hantavirus, adenovirus, CMV)
• SARS
• Ornithosis
• Pseudomonas aeruginosa: causes ventilator-associated pneumonia

• Definition: Aspiration is the inhalation of foreign material into the respiratory tract. It most commonly occurs after instrumentation of the upper airways or esophagus (e.g., upper GI endoscopy) or secondary to vomiting and regurgitation of gastric contents.
  • Aspiration pneumonitis
    • Aspiration of gastric acid that initially causes tracheobronchitis, with rapid progression to chemical pneumonitis
    • May cause ARDS in extreme cases
• Risk factors
  • Altered consciousness: alcohol, sedation, general anesthesia; , stroke
  • Apoplexy and neurodegenerative conditions
  • Gastroesophageal reflux disease, esophageal motility disorders
  • Congenital defects (e.g., tracheoesophageal fistula)
• Pathogens: mixed infections with anaerobic organisms are common; (e.g., Klebsiella spp.)
• Clinical findings
  • Immediate symptoms: bronchospasms; , crackles on auscultation, hypoxemia with cyanosis
  • Late symptoms: fever, shortness of breath, cough with foul-smelling sputum
• Diagnosis
  • Arterial blood gas analysis (↓ PaO₂, pH < 7.35, PaCO₂ > 45 mm Hg)
  • Radiologic imaging: The lung region in which the infiltrates are seen depends on the patient's position on aspiration.
    • Supine position: superior segment of the right lower lobe (most common site of aspiration)
    • Standing/sitting: posterior basal segment of the right lower lobe
    • Right lateral decubitus position: posterior segment of the right upper lobe or right middle lobe
• Management
  • If secondary to extubation: Immediate (re)intubation with administration of 100% O₂
  • Endotracheal suction with microbiological analysis of bronchial secretions
  • Antibiotic treatment that covers anaerobes (e.g., ampicillin-sulbactam, carbapenems, or clindamycin)
  • Regular monitoring: arterial blood gas, radiologic imaging
• Prevention: Optimize treatment and/or prophylaxis of underlying causes to reduce the risk of aspiration (e.g., elevation of the head of the bed).

References:^[24]

• Parapneumonic pleuritis
  • Fibrinous pleuritis: inflammation → increased vessel permeability → fibrin-rich exudate deposited on the serosal surface of the pleura
    • May manifest with pleuritic chest pain; and friction rub
  • Analgesics can be used for relief of symptoms.
• Parapneumonic pleural effusion (common)
• Pleural empyema
• Sepsis
• Respiratory failure, ARDS
• Lung abscess

References:^{[25][26][27][28]}

We list the most important complications. The selection is not exhaustive.

• Definition: a localized collection of pus and necrotic tissue within lung parenchyma caused by microbial infection
• Risk factors
  • Predisposition to aspiration due to reduced level of consciousness (see risk factors for “Aspiration pneumonia” above)
  • Bronchial obstruction (e.g., lung cancer, foreign body aspiration, bronchial stenosis)
  • Immunocompromised state
  • Pneumonia
• Pathogens
  • Most commonly: mixed infections caused by anaerobic bacteria that colonize the oral cavity (e.g., Peptostreptococcus, Prevotella, Bacteroides, Fusobacterium spp.)
  • Less commonly: monomicrobial lung abscess caused by S. aureus, Klebsiella pneumoniae, Streptococcus pyogenes, Streptococcus anginosus
• Clinical findings: indolent presentation with symptoms that evolve over weeks to months
  • Fever
  • Cough with production of foul-smelling sputum
  • Anorexia, weight loss
  • Night sweats
  • Hemoptysis
• Diagnosis
  • Gram stain, culture, and sensitivity of expectorated sputum
  • Radiologic imaging (x-ray or CT): irregular rounded cavity with an air-fluid level that is dependent on body position (most commonly in the right lung)
    • Upright position: right lower lobe
    • Recumbent position: right upper or middle lobe
• Management
  • Antibiotic treatment that covers anaerobes; (e.g., ampicillin-sulbactam, carbapenems, or clindamycin )
  • If medical therapy fails, percutaneous catheter drainage or surgical resection (e.g., segmentectomy or lobectomy) may be considered.

References:^[29][30]

• Mortality increases with age.
• The mortality risk can be evaluated with the CURB-65 score.
  • Score 0: ∼ 1%
  • Score 1–2: ∼ 10%
  • Score 3: ∼ 14%
  • Score 4: ∼ 40%
• HAP is associated with a mortality rate of > 20%.

References:^[31][32]

• Pneumococcal vaccination
• Influenza vaccination
• Smoking cessation

References:^[33][34][35]