Pneumonia

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Pneumonia

Definition & Classification

Pneumonia is an infection of the alveolar (gas-exchanging) portion of the lung. It is classified by the setting in which it is acquired, since this strongly predicts likely pathogens and guides empiric antibiotic choice:

Classification	Criteria
Community-acquired (CAP)	Acute pulmonary infection in a patient not hospitalized or in long-term care for ≥14 days before presentation
Hospital-acquired (HAP)	New infection occurring ≥48 h after hospital admission
Ventilator-acquired (VAP)	New infection ≥48 h after endotracheal intubation
Healthcare-associated (HCAP)	Hospitalized ≥2 days in last 90 days; nursing home residents; home IV antibiotics; dialysis; wound care; chemotherapy; immunocompromised

Tintinalli's Emergency Medicine, Table 65-1

Epidemiology

CAP causes approximately 3 million cases and 1.6 million hospitalizations per year in the United States. Mortality is <5% in outpatients but rises to 12-40% in hospitalized patients, and up to 29% in the sickest (PSI class V). It is the eighth leading cause of death overall and the leading cause of infection-related death in patients over 65.

Harrison's Principles of Internal Medicine 22E, Chapter 131

Pathophysiology

Organisms reach the lung primarily by aspiration of oropharyngeal secretions (most common) or by inhalation of aerosolized particles. Hematogenous spread (e.g., S. aureus, S. pneumoniae) is less common. Once in the alveoli, bacteria trigger an intense inflammatory response causing:

Filling of air spaces with exudate and WBCs (consolidation)
Spread through the bronchial tree and via alveolar pores (Kohn)
Possible pleural involvement (pleuritic chest pain)

Risk factors include aspiration predisposition (stroke, seizures, NG tube), impaired mucociliary clearance (COPD, smoking), and bacteremia risk (indwelling devices, debilitation).

Causative Organisms

Community-Acquired Pneumonia (most common)

Streptococcus pneumoniae - most common bacterial cause overall; classic lobar pattern, rusty sputum, rigors
Atypical organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp.) - lack cell wall, do not respond to beta-lactams; treated with macrolides or fluoroquinolones
Haemophilus influenzae - elderly, COPD, immunocompromised
Staphylococcus aureus - post-viral (influenza), CA-MRSA risk with structural lung disease or healthcare exposure
Klebsiella pneumoniae - alcoholics, elderly, aspiration risk; classic "currant-jelly sputum" (rarely seen in practice)
Viruses - influenza A/B, RSV, parainfluenza, adenovirus, SARS-CoV-2

Epidemiologic clues to pathogens (from Harrison's, Table 131-2):

Exposure / Risk	Consider
Alcoholism	S. pneumoniae, oral anaerobes, Klebsiella, M. tuberculosis
COPD / smoking	H. influenzae, Pseudomonas, Legionella, S. pneumoniae, Moraxella
Structural lung disease (bronchiectasis)	Pseudomonas, Burkholderia, S. aureus
Stroke / decreased consciousness	Oral anaerobes, gram-negative enteric bacteria
Hotel / cruise ship exposure	Legionella
Bird exposure	Histoplasma, Chlamydia psittaci
Southwestern US travel	Hantavirus, Coccidioides
Exposure to SARS-CoV-2 contacts	SARS-CoV-2

Clinical Features

Typical (bacterial) pneumonia:

Abrupt onset of fever, rigors, pleuritic chest pain
Productive cough (purulent or rusty sputum)
Tachypnea, tachycardia, hypoxia
Exam: dullness to percussion, tubular breath sounds, rales over affected area

Atypical pneumonia:

More gradual onset, dry cough, constitutional symptoms (headache, myalgias)
Physical exam findings may be minimal despite extensive chest X-ray changes ("walking pneumonia")

Viral pneumonia:

Interstitial pattern on imaging (bilateral diffuse infiltrates)
Hyaline membrane formation histologically
Limited auscultatory findings on exam

Severity Assessment and Site of Care

Two tools are widely used:

CURB-65 (5 variables, 1 point each)

Variable	Criterion
Confusion	New disorientation
Urea	BUN >7 mmol/L (>19 mg/dL)
Respiratory rate	≥30 breaths/min
Blood pressure	Systolic ≤90 or diastolic ≤60 mmHg
Age	≥65 years

Score 0: outpatient (30-day mortality ~1.5%)
Score 1-2: consider inpatient (unless age alone drives the score)
Score ≥3: high mortality (~22%), consider ICU

PSI (Pneumonia Severity Index)

Uses 20 variables (age, comorbidities, labs, physical findings) to assign risk class I-V. More accurate than CURB-65 but harder to calculate at the bedside. Mortality by class: I (0.1%), II (0.6%), III (2.8%), IV (8.2%), V (29.2%).

ICU admission criteria (ATS/IDSA minor criteria)

Direct ICU admission for septic shock or need for mechanical ventilation. Consider ICU/high-monitoring unit if ≥3 of the following:

Respiratory rate ≥30/min
PaO2/FiO2 ≤250
Multilobar infiltrates
Confusion/disorientation
BUN ≥20 mg/dL
Leukopenia (WBC <4,000)
Thrombocytopenia (<100,000)
Hypothermia (<36°C)
Hypotension requiring aggressive fluid resuscitation
Harrison's Principles of Internal Medicine 22E, Chapter 131

Treatment

Initial therapy is empirical since the causative organism is rarely identified at presentation. Coverage is guided by severity, comorbidities, and risk for drug-resistant organisms (MRSA, Pseudomonas).

Outpatient CAP (no comorbidities)

Macrolide (azithromycin, clarithromycin) OR
Doxycycline

Outpatient CAP (with comorbidities: cardiac/pulmonary/hepatic/renal disease, diabetes, alcoholism, malignancy, asplenia)

Respiratory fluoroquinolone (levofloxacin 750 mg/day x5d; moxifloxacin 400 mg/day) OR
Beta-lactam (amoxicillin-clavulanate 2 g twice daily or 3rd-gen cephalosporin) plus macrolide/doxycycline

Inpatient (non-ICU)

Beta-lactam + macrolide OR
Respiratory fluoroquinolone monotherapy

Inpatient (ICU)

Beta-lactam + azithromycin OR beta-lactam + respiratory fluoroquinolone
Add MRSA coverage (vancomycin or linezolid) if: prior respiratory isolation of MRSA, or recent hospitalization + IV antibiotics
Add Pseudomonas coverage if: structural lung disease, prior Pseudomonas isolation, or recent hospitalization + IV antibiotics

Algorithm for MRSA/Pseudomonas risk assessment in CAP

FIGURE: ATS/IDSA algorithm for assessing inpatient MRSA and Pseudomonas aeruginosa risk in CAP (Harrison's Principles of Internal Medicine 22E)

Atypical agents

Because Mycoplasma, Chlamydia, and Legionella lack a cell wall, beta-lactams are ineffective. Use macrolides or respiratory fluoroquinolones. Note: macrolide-resistant Mycoplasma is increasing globally (up to 95% in China, 5-13% in the US). - Tintinalli's Emergency Medicine, Chapter 65

Aspiration pneumonia

Routine anaerobic coverage is not needed unless:

Poor dentition
Lung abscess present
Necrotizing pneumonia (treat 3-12 weeks with systemic antibiotics)

Antibiotic Resistance - Key Points

S. pneumoniae: resistance to beta-lactams via altered penicillin-binding proteins; increasing macrolide resistance
CA-MRSA: risk in post-influenza, structural lung disease; associated with Panton-Valentine leukocidin (PVL) causing severe necrotizing infection - must be recognized early
ESBLs / gram-negatives: fluoroquinolone-resistant E. coli increasing; ESBL-producers warrant carbapenem consideration
Fluoroquinolone caution: CDC recommends reserving for patients failing first-line therapy, documented resistance, or contraindications to alternatives; contraindicated in myasthenia gravis

Recent Evidence (2024-2026)

A 2025 meta-analysis (PMID 40107661) identified key risk factors for drug-resistant pathogens in CAP, supporting targeted antibiotic selection based on individual patient risk profiles.
A 2025 Lancet Respiratory Medicine analysis (PMID 39892408) examined adjuvant corticosteroids in CAP, finding benefit in select subgroups (particularly those with high inflammatory markers) but not all patients.
A 2024 meta-analysis in Pediatric Pulmonology (PMID 39239917) confirmed lung ultrasound is at least as accurate as chest X-ray for diagnosing CAP in children, supporting its growing use to reduce radiation exposure.

Sources: Harrison's Principles of Internal Medicine 22E (Chapter 131), Tintinalli's Emergency Medicine (Chapter 65), Fishman's Pulmonary Diseases and Disorders (Chapter 122), Jawetz, Melnick & Adelberg's Medical Microbiology 28E (Chapter 48)

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