What is the recommended treatment for community-acquired pneumonia (CAP)?

Treatment of Community-Acquired Pneumonia

Outpatient Treatment (No Comorbidities)

Amoxicillin 1 g orally three times daily is the preferred first-line therapy for healthy adults without comorbidities, based on strong evidence demonstrating effectiveness against common CAP pathogens including penicillin-resistant Streptococcus pneumoniae. 1, 2

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries lower quality evidence 1, 2
• Some experts recommend starting doxycycline with a 200 mg loading dose to achieve adequate serum levels more rapidly 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2
• Avoid macrolide monotherapy in areas with high resistance rates (>25%) as this leads to treatment failure and promotes further resistance 2, 3

Outpatient Treatment (With Comorbidities)

For adults with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia), use combination therapy with a β-lactam plus macrolide or doxycycline, OR respiratory fluoroquinolone monotherapy. 1, 2

Combination Therapy Option:

• Amoxicillin-clavulanate 2 g twice daily PLUS azithromycin 500 mg daily OR clarithromycin 500 mg twice daily OR doxycycline 100 mg twice daily 1, 2
• Alternative β-lactams: cefpodoxime or cefuroxime 2

Fluoroquinolone Monotherapy Option:

• Levofloxacin 750 mg daily OR moxifloxacin 400 mg daily OR gemifloxacin 320 mg daily 1, 2
• However, fluoroquinolones should be reserved for patients with contraindications to β-lactams or macrolides due to FDA warnings about serious adverse events including tendon rupture, peripheral neuropathy, and aortic dissection 1, 4

Inpatient Treatment (Non-ICU)

For hospitalized patients without ICU-level severity, use either β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy—both regimens have equivalent strong evidence and high-quality support. 1, 2, 5

Preferred Combination Regimen:

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily 1, 2, 5, 3
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours, ampicillin-sulbactam 1.5-3 g IV every 6 hours, or ceftaroline 600 mg IV every 12 hours 1, 5
• Alternative macrolides: clarithromycin 500 mg twice daily 2

Fluoroquinolone Monotherapy:

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2, 5
• Meta-analyses show fluoroquinolones demonstrate fewer clinical failures and less diarrhea compared to β-lactam/macrolide combinations, though no mortality difference exists 5

For Penicillin-Allergic Patients:

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is the preferred alternative 1, 2
• Alternative: aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 2

Inpatient Treatment (ICU/Severe CAP)

For ICU patients with severe CAP, mandatory combination therapy with β-lactam PLUS either azithromycin OR respiratory fluoroquinolone is required, as observational studies demonstrate mortality benefit with combination therapy over monotherapy. 1, 2, 5

Standard ICU Regimen:

• Ceftriaxone 2 g IV daily OR cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours 1, 2, 5
• PLUS azithromycin 500 mg IV daily OR levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2, 5

For Penicillin-Allergic ICU Patients:

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily) PLUS aztreonam 2 g IV every 8 hours 2

Special Populations Requiring Expanded Coverage

Risk Factors for Pseudomonas aeruginosa:

Add antipseudomonal coverage if the patient has structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1, 2, 5

• Antipseudomonal β-lactam: piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem 500 mg IV every 6 hours, OR meropenem 1 g IV every 8 hours 1, 2, 5
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1, 2, 5
• Alternative: antipseudomonal β-lactam PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 500 mg daily 1, 2

Risk Factors for MRSA:

Add MRSA coverage if the patient has prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1, 2, 5

• Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 1, 2, 5
• Add to the standard CAP regimen, do not substitute 2, 5

Duration of Therapy

Treat for a minimum of 5 days AND until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability (heart rate ≤100/min, systolic BP ≥90 mmHg, respiratory rate ≤24/min, oxygen saturation ≥90%, able to take oral intake, normal mental status). 1, 2, 5, 3

• Typical duration for uncomplicated CAP is 5-7 days 1, 2, 5
• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 2, 3
• For severe microbiologically undefined pneumonia, 10 days of treatment is recommended 2

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to ingest medications, and has normal GI function—typically by day 2-3 of hospitalization. 1, 2, 5

• Oral step-down options: amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily 2
• Alternative: levofloxacin 750 mg daily or moxifloxacin 400 mg daily 2, 5
• The tissue half-life of azithromycin allows for continued antimicrobial effect even after oral transition 2

Critical Pitfalls to Avoid

Never use the same antibiotic class if the patient had recent exposure (within 3 months) due to dramatically increased resistance risk—switch to a different class entirely. 1, 5

Administer the first antibiotic dose in the emergency department immediately upon diagnosis, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients. 2, 3

Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 2, 5

Never use macrolide monotherapy in hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 2

Do not extend therapy beyond 7 days in responding patients without specific indications (such as Legionella, S. aureus, or Gram-negative bacilli), as this increases antimicrobial resistance risk without clinical benefit. 2, 5

Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment (antiviral therapy) and infection prevention strategies. 3

Once reliable microbiological identification occurs, narrow to pathogen-directed therapy rather than continuing empiric broad-spectrum coverage. 5