Pneumonia - Comprehensive Medical Student Overview

Definition

Classification

Epidemiology

• CAP is the most common infectious cause of hospitalization and death in the United States
• ~7 health care visits/1000 young adults vs. 96 visits/1000 adults aged ≥85 years
• Hospitalization rates nearly 40/1000 in adults ≥85 years old
• ~35% of hospitalizations involve patients with recent health care exposure
• Pneumonia is the primary diagnosis in over 1 million hospital admissions per year in the U.S., with an in-hospital death rate of 3.3%
• Incidence peaks November to March (coinciding with influenza and respiratory viruses)
• SARS-CoV-2 became the leading infectious cause of death during the COVID-19 pandemic
• Goldman-Cecil Medicine; Textbook of Family Medicine 9e

Etiology and Pathogens

Typical vs. Atypical

• Streptococcus pneumoniae (pneumococcus) - most common overall
• Haemophilus influenzae - especially in COPD patients
• Staphylococcus aureus - post-influenza, ICU
• Gram-negative bacilli (Klebsiella, Pseudomonas, E. coli) - in nursing home, structural lung disease

• Mycoplasma pneumoniae - most common atypical, especially young adults
• Chlamydophila pneumoniae
• Legionella pneumophila - water exposure, hyponatremia, severe disease

• Influenza A and B, RSV, SARS-CoV-2, human metapneumovirus
• Respiratory viruses historically caused 20-30% of cases (higher during COVID-19 pandemic)

• Pneumocystis jirovecii (PCP) - HIV with CD4 <200
• Cryptococcus, Aspergillus, endemic fungi (Coccidioides, Histoplasma)

Pathogens by Setting (Fishman's Pulmonary Diseases)

• Drug-resistant S. pneumoniae (DRSP): Age >65, β-lactam therapy within past 3 months, alcoholism, immunosuppression, multiple comorbidities, daycare exposure
• Pseudomonas: Structural lung disease (bronchiectasis), steroids >10 mg/day prednisone, broad-spectrum antibiotics for >7 days in past month, malnutrition

Pathophysiology

1. Colonization and aspiration - micro-aspiration of oropharyngeal bacteria is the most common route (hematogenous spread and inhalation are less common)
2. Host defense failure - impaired mucociliary clearance, alveolar macrophage dysfunction, or neutrophil impairment allows microbial proliferation
3. Alveolar inflammation - cytokine release recruits neutrophils; alveoli fill with exudate (fluid, fibrin, PMNs, RBCs)
4. Consolidation - affected lung segments become airless and solid (classic lobar or bronchopneumonia pattern)
5. Impaired gas exchange - ventilation-perfusion (V/Q) mismatch leads to hypoxemia

1. Congestion (first 24 h) - vascular engorgement, intra-alveolar fluid
2. Red hepatization (days 2-3) - lobe firm/airless, alveoli packed with fibrin, RBCs, neutrophils
3. Gray hepatization (days 4-6) - RBCs lyse; fibrin and PMNs remain
4. Resolution - fibrin digested, alveoli cleared

Clinical Presentation

Typical (Bacterial) Pattern

• Abrupt onset of high fever, chills/rigors
• Productive cough - purulent, blood-tinged, or "rusty" sputum (classic for pneumococcus)
• Pleuritic chest pain - sharp, worse with breathing
• Dyspnea, malaise
• WBC often >15,000 × 10³/mm³ with neutrophil predominance

• Dullness to percussion
• Decreased breath sounds over affected lobe
• Egophony ("e" sounds like "a")
• Bronchial breath sounds and increased tactile fremitus
• Crackles (crepitations)

Atypical Pattern

• Gradual onset over days to weeks
• Low-grade fever
• Non-productive (dry) cough
• Fewer constitutional symptoms; patient may appear surprisingly well
• Headache, myalgia, sore throat preceding respiratory symptoms (Mycoplasma)
• X-ray findings often worse than clinical exam suggests ("walks around with pneumonia")

Diagnosis

Chest Imaging

• Chest X-ray - required to confirm; shows consolidation (opacification), interstitial infiltrates, or lobar involvement
• CT chest - more sensitive; used for complicated or atypical presentations

Laboratory Work

• CBC: Leukocytosis with left shift (bacterial); lymphopenia (viral)
• CMP: Assess renal function (for severity scoring), electrolytes (hyponatremia - think Legionella)
• Blood cultures x 2 - before antibiotics in hospitalized patients
• Sputum Gram stain and culture - expectorated or endotracheal (low sensitivity/specificity but can guide therapy)
• Urinary antigen tests:
  • Legionella urinary antigen - high sensitivity/specificity, detects serogroup 1
  • Pneumococcal urinary antigen - useful in moderate-severe disease
• Procalcitonin - elevated in bacterial pneumonia; guidelines currently recommend against using it alone to decide whether to give antibiotics
• PCR panels (multiplex) - increasingly used, improve pathogen identification
• HIV testing in appropriate patients (risk-stratified)

Microbiologic Yield

• In over 50% of cases, no pathogen is definitively identified
• Blood cultures positive in only ~5-10% of hospitalized CAP patients

Severity Assessment and Admission Decision

PSI (Pneumonia Severity Index / PORT Score)

CURB-65 (simpler, bedside tool)

• Confusion (new)
• Urea >7 mmol/L (BUN >19 mg/dL)
• Respiratory rate ≥30/min
• Blood pressure <90 systolic or ≤60 diastolic mmHg
• Age 65 years or older

Severe CAP Criteria (ATS/IDSA)

• 1 major criterion: Septic shock needing vasopressors, or respiratory failure needing mechanical ventilation
• OR ≥3 minor criteria: RR ≥30, PaO₂/FiO₂ ≤250, multilobar infiltrates, confusion, BUN ≥20 mg/dL, WBC <4000, platelets <100,000, hypothermia, hypotension needing fluids

Treatment

Outpatient CAP (5-day course)

Inpatient CAP (non-ICU)

• Respiratory fluoroquinolone (levofloxacin, moxifloxacin) as monotherapy, OR
• β-lactam + macrolide/doxycycline combination

Severe CAP (ICU)

• β-lactam + macrolide, OR
• β-lactam + respiratory fluoroquinolone
• Add MRSA coverage (vancomycin or linezolid) if risk factors for MRSA
• Add anti-pseudomonal coverage (pip-tazo, cefepime, meropenem) if P. aeruginosa risk

HAP/VAP

• Cover S. aureus, Pseudomonas, and other gram-negative bacilli
• Add MRSA coverage if local MRSA prevalence >10-20% or risk factors present
• Consider two anti-pseudomonal agents from different classes if MDR risk
• De-escalate to monotherapy once culture data available

Viral Pneumonia

• SARS-CoV-2: Antivirals (e.g., remdesivir) and/or monoclonal antibodies in higher-risk patients; no antibacterials unless bacterial coinfection suspected
• Influenza: Oseltamivir - start empirical antibiotics concurrently due to risk of bacterial coinfection

Complications

Prevention

Pneumococcal Vaccines

• PCV15 or PCV20 (conjugate) recommended for all adults ≥65 and high-risk groups
• PPSV23 (polysaccharide) for immunocompromised, functional or anatomic asplenia, and certain high-risk conditions
• High-risk groups include: Chronic heart/lung/liver disease, DM, alcoholism, asplenia, immunodeficiency (HIV, leukemia, lymphoma, transplant), CSF leak, cochlear implant, nephrotic syndrome

Other Vaccines

• Influenza vaccine - annually for all adults ≥50 and those with chronic lung disease, DM, immunodeficiency, or other chronic organ failure
• COVID-19 vaccine (updated formulations)

Key High-Yield Points for Exams

• Pneumococcus = most common cause of CAP overall
• Mycoplasma = most common atypical; young, healthy adults; dry cough; extrapulmonary features (cold agglutinins, hemolytic anemia, bullous myringitis)
• Legionella = water/cooling towers; hyponatremia, elevated LFTs, GI symptoms; diagnose with urinary antigen; treat with fluoroquinolones or macrolides
• Klebsiella = alcoholics, "currant jelly sputum," upper lobe cavitating
• PCP (P. jirovecii) = HIV/CD4 <200; bilateral interstitial infiltrates; treat with TMP-SMX
• Staphylococcal pneumonia = post-influenza; cavitary lesions; bilateral; can cause empyema/abscess
• Aspiration = right lower lobe (upright) or right upper lobe posterior segment (supine); anaerobes
• CURB-65 ≥2 = consider hospitalization
• PSI class I-III = outpatient; class IV-V = inpatient
• Respiratory fluoroquinolones should NOT be used as monotherapy in community when TB is possible (can mask/delay diagnosis)

Recent Evidence (2024-2025)

1. Corticosteroids in non-viral CAP (Intensive Care Med, 2025 - PMID 40323455): Adjuvant corticosteroids in hospitalized non-viral CAP patients may reduce treatment failure and length of stay - an evolving area with potential guideline implications.
2. Drug-resistant pathogens in CAP (Eur Respir Rev, 2025 - PMID 40107661): A systematic review identified key risk factors for MDR organisms in CAP, reinforcing the importance of stratified empiric therapy.