What is the approach to diagnosis and treatment for pneumonitis versus community-acquired pneumonia (CAP)?

Distinguishing Pneumonitis from Community-Acquired Pneumonia

Pneumonitis and community-acquired pneumonia (CAP) are fundamentally different entities: pneumonitis refers to non-infectious lung inflammation (chemical, drug-induced, hypersensitivity, or aspiration-related), while CAP is an infectious process requiring antimicrobial therapy—the critical distinction lies in identifying infectious versus inflammatory etiology to avoid unnecessary antibiotics in pneumonitis or delayed treatment in CAP.

Key Diagnostic Distinctions

Clinical Context and History

• Pneumonitis typically presents with exposure history: recent aspiration event, new medications (amiodarone, methotrexate, nitrofurantoin), inhalational exposures, or radiation therapy 1
• CAP presents with acute infectious symptoms: fever >38°C or hypothermia ≤36°C, new or increased cough, dyspnea, leukocytosis >10,000/μL or leukopenia <4,000/μL, and purulent sputum 2
• The absence of fever and infectious symptoms with a clear exposure history strongly suggests pneumonitis over CAP 1

Radiographic Patterns

• Both conditions require chest radiography for diagnosis, but patterns differ 1, 3
• Pneumonitis often shows diffuse, bilateral interstitial or ground-glass opacities in characteristic distributions (aspiration: dependent segments; drug-induced: diffuse or upper lobe predominant)
• CAP typically demonstrates focal air space consolidation, though this can be multilobar in severe cases 3
• Chest X-ray remains the standard for confirming pneumonia, though clinical diagnosis alone is acceptable in mild outpatient cases 1

Diagnostic Approach for CAP

When to Pursue Microbial Diagnosis

• Outpatients: Do NOT obtain routine sputum cultures, blood cultures, or urine antigen testing 1
• Hospitalized patients (non-severe): Blood cultures prior to antibiotics; sputum Gram stain and culture only if high-quality specimen can be rapidly processed 3, 4
• Severe CAP (septic shock requiring vasopressors OR respiratory failure requiring mechanical ventilation): Obtain pretreatment sputum cultures, blood cultures, AND urine antigens for pneumococcus and Legionella 1
• Test ALL patients for COVID-19 and influenza when these viruses are circulating in the community, as results directly affect treatment decisions 2

Critical Limitation to Recognize

• Up to 50% of CAP patients never have a pathogen identified despite extensive testing 1
• Clinical characteristics cannot reliably distinguish bacterial from atypical pathogens—the traditional "typical" versus "atypical" classification has limited clinical value 1
• Only 38% of hospitalized CAP patients have a pathogen identified; of those, up to 40% are viral and only 15% are Streptococcus pneumoniae 2

Treatment Algorithm for CAP

Severity Assessment Determines Everything

• Use Pneumonia Severity Index (PSI) or CURB-65 to determine hospitalization need 1, 3
• Severe CAP criteria (requiring ICU admission): Septic shock requiring vasopressors OR respiratory failure requiring mechanical ventilation 1
• Initiate empiric antibiotics immediately—do NOT delay for diagnostic testing; therapy should begin within 8 hours of hospital arrival 3

Empiric Antibiotic Selection

Healthy outpatients without comorbidities:

• First-line: Amoxicillin OR doxycycline 3
• Macrolide (azithromycin or clarithromycin) ONLY if local pneumococcal macrolide resistance is <25% 3

Outpatients with comorbidities (COPD, diabetes, heart disease, chronic kidney disease):

• Amoxicillin/clavulanate OR cephalosporin PLUS macrolide (azithromycin or clarithromycin) 3

Hospitalized patients (non-severe):

• Parenteral β-lactam (ceftriaxone or cefotaxime) PLUS macrolide (azithromycin or clarithromycin) 3, 2
• β-lactam/macrolide combination has stronger evidence than β-lactam/fluoroquinolone 1
• Minimum treatment duration: 3-5 days with clinical stability required before discontinuation 1, 2

Severe CAP (ICU patients):

• β-lactam (cefotaxime, ceftriaxone, or piperacillin/tazobactam) PLUS macrolide OR respiratory fluoroquinolone 3
• Add MRSA coverage (vancomycin or linezolid) if: prior MRSA infection, recent hospitalization with IV antibiotics, or high local MRSA prevalence 1
• Add Pseudomonas coverage (piperacillin/tazobactam, cefepime, or meropenem) if: prior Pseudomonas infection, structural lung disease (bronchiectasis), or recent hospitalization with IV antibiotics 1
• Consider systemic corticosteroids within 24 hours of severe CAP development—may reduce 28-day mortality 2

Duration and Transition

• Minimum 5 days for all CAP patients; treatment beyond 7 days not generally recommended except for proven P. aeruginosa infection (15 days appropriate) 3
• Switch to oral therapy when: improvement in cough and dyspnea, afebrile, decreasing white blood cell count, and functioning GI tract with adequate oral intake 3

Management of Pneumonitis

For confirmed pneumonitis (non-infectious inflammation):

• Do NOT initiate antibiotics—this is the fundamental management difference
• Remove or discontinue the offending agent (stop causative medication, avoid exposure)
• Supportive care with oxygen supplementation as needed
• Consider corticosteroids for drug-induced or hypersensitivity pneumonitis (not applicable to CAP except severe cases)
• Monitor for secondary bacterial infection, which would then require antibiotic therapy as per CAP guidelines

Critical Pitfalls to Avoid

• Do NOT delay antibiotics in suspected CAP while pursuing diagnostic testing—empiric therapy must begin immediately 3
• Do NOT rely on sputum Gram stain alone to guide initial therapy—it cannot identify atypical pathogens (Mycoplasma, Chlamydia, Legionella) and has poor predictive value 3
• Do NOT use acute-phase reactants (ESR, CRP, procalcitonin) as sole determinants to distinguish viral from bacterial CAP 3
• Do NOT routinely obtain follow-up chest radiographs in patients who achieve clinical stability, but consider lung cancer screening if eligible 1
• Recognize that chest radiography may not detect early pneumonia, creating diagnostic uncertainty between pneumonia and bronchitis 5, 3
• Be aware that azithromycin can cause QT prolongation, hepatotoxicity, and Clostridium difficile-associated diarrhea—weigh risks carefully in at-risk patients 6