What is the recommended 5-day treatment regimen for mild to moderate community-acquired pneumonia?

5-Day Treatment for Community-Acquired Pneumonia

For mild to moderate community-acquired pneumonia, a 5-day treatment regimen is appropriate using either levofloxacin 750 mg once daily or standard-dose antibiotics (amoxicillin, doxycycline, or azithromycin) with treatment duration guided by clinical stability criteria rather than a fixed calendar duration. 1

Treatment Selection Algorithm

For Previously Healthy Adults WITHOUT Comorbidities

First-line options (5-day duration acceptable):

• Amoxicillin 1 g three times daily - This is the preferred first-line agent with strong recommendation and moderate quality evidence 2, 1
• Doxycycline 100 mg twice daily - Alternative option with conditional recommendation and low quality evidence 2
• Azithromycin 500 mg day 1, then 250 mg daily (total 5 days) - Only use in areas where pneumococcal macrolide resistance is <25% 2, 3

For Adults WITH Comorbidities

(Chronic heart/lung/liver/renal disease, diabetes, alcoholism, malignancy, asplenia, age >65, recent antibiotic use)

Combination therapy (5-7 days):

• Amoxicillin/clavulanate 875 mg/125 mg twice daily PLUS azithromycin (500 mg day 1, then 250 mg daily) 2, 1
• OR Amoxicillin/clavulanate 2,000 mg/125 mg twice daily PLUS doxycycline 100 mg twice daily 2

Monotherapy alternative:

• Levofloxacin 750 mg once daily for 5 days - This high-dose, short-course regimen is FDA-approved specifically for 5-day treatment of CAP 4, 5
• Alternative: Moxifloxacin 400 mg daily for 5 days 2

Clinical Stability Criteria for 5-Day Treatment

You must extend therapy beyond 5 days ONLY if the patient has NOT achieved ALL of the following by day 5: 1

• Temperature ≤37.8°C (100°F)
• Heart rate ≤100 beats/min
• Respiratory rate ≤24 breaths/min
• Systolic blood pressure ≥90 mmHg
• Oxygen saturation ≥90% on room air
• Ability to maintain oral intake
• Normal mental status

If all stability criteria are met by day 5, discontinue antibiotics. 1 Treatment should generally not exceed 8 days in a responding patient. 1

Evidence Supporting 5-Day Regimens

Levofloxacin 750 mg High-Dose Short-Course

The FDA label specifically approves levofloxacin 750 mg once daily for 5 days for CAP caused by S. pneumoniae (excluding MDRSP), H. influenzae, H. parainfluenzae, M. pneumoniae, or C. pneumoniae. 4

In a pivotal double-blind trial of 528 patients, levofloxacin 750 mg for 5 days achieved 90.9% clinical success versus 91.1% for levofloxacin 500 mg for 10 days, demonstrating non-inferiority. 4, 5 The high-dose regimen maximizes concentration-dependent bactericidal activity and may reduce resistance emergence. 5, 6

For atypical pathogens specifically, the 750 mg 5-day course achieved 95.5% clinical success and resulted in significantly more rapid fever resolution by day 3 compared to the 10-day regimen. 7

Standard-Dose Antibiotics

The American Thoracic Society guidelines support a minimum 5-day duration for standard antibiotics (amoxicillin, doxycycline, macrolides) when clinical stability criteria are met. 1 This represents a shift from older fixed-duration approaches to response-guided therapy.

Critical Pitfalls to Avoid

Do NOT use azithromycin monotherapy if: 3

• Patient has comorbidities or risk factors
• Local macrolide resistance ≥25%
• Patient received antibiotics in past 3 months
• Patient requires hospitalization

Do NOT use 5-day regimens for: 1

• Suspected or confirmed Legionella pneumophila (requires 14-21 days)
• Suspected or confirmed Staphylococcus aureus (requires 14-21 days)
• Gram-negative enteric bacilli (requires 14-21 days)
• Multi-drug resistant S. pneumoniae (use 7-14 day regimen with levofloxacin 500 mg) 4

Fluoroquinolone cautions: 1 Reserve fluoroquinolones for patients with comorbidities or when other options cannot be used due to risks of tendinopathy, peripheral neuropathy, and CNS effects. Check QTc interval before initiating therapy; avoid if QTc >450 ms (men) or >470 ms (women). 3

Monitoring Response

Fever should resolve within 2-3 days after initiating treatment. 1 If no clinical improvement by day 2-3, reassess for alternative diagnoses, complications, or resistant pathogens rather than automatically extending duration. 1 The key is achieving clinical stability, not completing an arbitrary calendar duration.