What is the current inpatient treatment for Community-Acquired Pneumonia (CAP)?

Current Inpatient Treatment for Community-Acquired Pneumonia

For hospitalized adults with CAP without risk factors for MRSA or Pseudomonas, use either combination therapy with a β-lactam plus macrolide OR respiratory fluoroquinolone monotherapy as first-line empiric treatment. 1

Standard Inpatient Empiric Regimens (Non-ICU)

The 2019 ATS/IDSA guidelines provide two equally preferred options with strong recommendations 1:

Option 1: β-lactam + Macrolide Combination

• Ampicillin-sulbactam 1.5-3 g IV every 6 hours PLUS
• Azithromycin 500 mg daily OR Clarithromycin 500 mg twice daily 1

Alternative β-lactams (same strength of recommendation):

• Cefotaxime 1-2 g IV every 8 hours 1
• Ceftriaxone 1-2 g IV daily 1
• Ceftaroline 600 mg IV every 12 hours 1

Option 2: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750 mg IV/PO daily 1, 2
• Moxifloxacin 400 mg IV/PO daily 1

Both regimens have strong recommendations with high-quality evidence and show similar mortality outcomes in systematic reviews 1. Fluoroquinolone monotherapy demonstrated fewer clinical failures and less diarrhea in meta-analysis of 16 RCTs involving 4,809 patients, though mortality differences were not significant 1.

Option 3: β-lactam + Doxycycline (For Macrolide/Fluoroquinolone Contraindications)

• β-lactam (doses as above) PLUS
• Doxycycline 100 mg IV/PO twice daily 1, 3

This carries only conditional recommendation with low-quality evidence and should be reserved for patients with contraindications to both macrolides and fluoroquinolones 1.

Severe CAP Requiring ICU Admission

For ICU patients, β-lactam plus macrolide combination is preferred over fluoroquinolone monotherapy due to mortality benefit in observational studies. 1

Standard ICU Regimen:

• β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam at doses above) PLUS
• Azithromycin 500 mg daily 1

OR

• β-lactam PLUS
• Respiratory fluoroquinolone (levofloxacin 750 mg or moxifloxacin 400 mg) 1

Risk Factors Requiring Expanded Coverage

For Pseudomonas aeruginosa Risk:

Use anti-pseudomonal β-lactam plus dual coverage 1:

• Piperacillin-tazobactam, cefepime, imipenem, or meropenem PLUS
• Ciprofloxacin or Levofloxacin 750 mg 1

OR

• Anti-pseudomonal β-lactam PLUS
• Aminoglycoside PLUS azithromycin or respiratory fluoroquinolone 1

For MRSA Risk:

Add vancomycin or linezolid to the standard regimen 1

Treatment Duration and Transition

Duration:

• Minimum 5 days of therapy 1
• Patient must be afebrile for 48-72 hours 1
• No more than 1 sign of clinical instability before discontinuation 1

IV to Oral Switch:

Switch when the patient is 1:

• Hemodynamically stable
• Clinically improving
• Able to ingest medications
• Has normally functioning GI tract

Discharge immediately after oral switch—inpatient observation while on oral therapy is unnecessary 1.

First Antibiotic Dose Timing:

Administer the first dose while still in the emergency department for all admitted patients 1.

Critical Caveats and Pitfalls

Antibiotic Class Rotation:

Never use the same antibiotic class if the patient had recent exposure (within 3 months) due to increased resistance risk 1. Switch to a different class entirely 1.

Doxycycline Limitations:

• Never use as monotherapy for hospitalized patients 3
• Must be combined with β-lactam for adequate pneumococcal coverage 3
• Not preferred for ICU patients—use macrolide or fluoroquinolone instead 3

Fluoroquinolone Considerations:

Despite FDA warnings about adverse events, fluoroquinolones remain justified for CAP due to excellent performance in clinical trials, low resistance rates, coverage of typical and atypical organisms, and relative rarity of serious adverse events 1. However, be aware of increasing reports of tendon rupture, peripheral neuropathy, and CNS effects 1.

Pathogen-Directed Therapy:

Once reliable microbiological identification occurs, narrow to pathogen-directed therapy rather than continuing empiric broad-spectrum coverage 1.

Adjunctive Therapies for Severe CAP:

• Screen hypotensive, fluid-resuscitated patients for occult adrenal insufficiency 1
• Use low tidal-volume ventilation (6 mL/kg ideal body weight) for patients with diffuse bilateral pneumonia or ARDS 1
• Consider noninvasive ventilation trial for hypoxemia unless severe hypoxemia (PaO₂/FiO₂ <150) with bilateral infiltrates requires immediate intubation 1