What is the recommended outpatient antibiotic regimen for an otherwise healthy adult with mild-to-moderate community-acquired pneumonia?

Outpatient Antibiotic Treatment for Mild-to-Moderate Community-Acquired Pneumonia in Healthy Adults

For an otherwise healthy adult with mild-to-moderate community-acquired pneumonia, prescribe amoxicillin 1 gram orally three times daily for 5–7 days as first-line therapy. 1

First-Line Therapy: Amoxicillin

• Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line antibiotic for previously healthy adults without comorbidities, based on strong recommendation and moderate-quality evidence from the 2019 IDSA/ATS guidelines. 1
• Amoxicillin retains activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, making it the most effective oral agent for the predominant bacterial pathogen in CAP. 1, 2
• This regimen provides superior pneumococcal coverage compared with oral cephalosporins and is endorsed by both U.S. and European guidelines as the standard for empirical outpatient treatment. 1, 2

Alternative Regimens When Amoxicillin Cannot Be Used

• Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin is contraindicated or not tolerated, offering coverage of both typical bacterial pathogens and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 2
• Doxycycline carries a conditional recommendation with lower-quality evidence compared to amoxicillin but provides reliable broad-spectrum coverage at significantly lower cost than fluoroquinolones. 1, 2

Macrolide Monotherapy: Use Only in Low-Resistance Areas

• Macrolide monotherapy (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
• In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, making macrolide monotherapy unsafe as first-line therapy due to the risk of breakthrough pneumococcal bacteremia with resistant strains. 1, 2
• Macrolide monotherapy should be avoided in patients with any comorbidities, recent antibiotic use, or those requiring hospitalization. 1

Fluoroquinolones: Reserved for Specific Situations

• Respiratory fluoroquinolones (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) should be reserved for patients with comorbidities or when other options cannot be used, due to FDA warnings about serious adverse events including tendinopathy, peripheral neuropathy, and aortic dissection. 1, 2
• Fluoroquinolones are active against >98% of S. pneumoniae strains, including penicillin-resistant isolates, but should not be used as first-line agents in uncomplicated outpatient pneumonia to preserve their efficacy and minimize resistance. 1, 3

Treatment Duration and Monitoring

• Treat for a minimum of 5 days and continue until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1, 2
• The typical total duration for uncomplicated CAP is 5–7 days. 1, 2
• Arrange a clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1, 2

Criteria for Treatment Failure and Escalation

• Indicators of treatment failure that warrant hospital referral include: no clinical improvement by day 2–3, development of respiratory distress (respiratory rate >30/min, oxygen saturation <92%), inability to tolerate oral antibiotics, or new complications such as pleural effusion. 1, 2
• If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to provide coverage for atypical pathogens. 1, 2
• If combination therapy (β-lactam + macrolide) fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in regions where pneumococcal macrolide resistance exceeds 25% (the situation in most of the United States), as this leads to treatment failure and breakthrough bacteremia. 1, 2
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient pneumonia due to safety warnings and resistance concerns; reserve for patients with comorbidities or treatment failure. 1, 2
• Oral cephalosporins (cefuroxime, cefpodoxime) are not first-line agents due to inferior in-vitro activity against S. pneumoniae, lack of atypical coverage, higher cost, and no demonstrated clinical superiority over amoxicillin. 1, 2
• Do not assume all pneumonia cases require atypical coverage; in previously healthy adults without severe illness, amoxicillin or doxycycline monotherapy provides adequate empiric therapy, with atypical coverage added only if the initial regimen fails. 1

Follow-Up and Prevention

• Routine follow-up at 6 weeks is recommended for all patients; obtain a chest radiograph only if symptoms persist, physical signs remain abnormal, or the patient has high risk for underlying malignancy (e.g., smokers >50 years). 1, 2
• Offer pneumococcal polysaccharide vaccination to all adults ≥65 years and those with high-risk conditions, and advise annual influenza vaccination for all patients. 1, 2
• Provide smoking-cessation counseling to every current smoker. 1, 2