What is the recommended antibiotic regimen for an adult with typical community‑acquired pneumonia who has no drug allergies, comorbidities, or recent antibiotic use?

Antibiotic Selection for Community-Acquired Pneumonia in Healthy Adults

For a previously healthy adult with typical community-acquired pneumonia and no drug allergies, comorbidities, or recent antibiotic use, prescribe amoxicillin 1 gram orally three times daily for 5–7 days as the first-line treatment. 1, 2

First-Line Therapy: Amoxicillin

Amoxicillin is the preferred agent because it retains activity against 90–95% of Streptococcus pneumoniae isolates—the most common bacterial pathogen in CAP—including many penicillin-resistant strains. 1, 2 This recommendation carries strong evidence with moderate quality from both the American Thoracic Society and Infectious Diseases Society of America. 1, 2 European respiratory societies and the CDC also endorse amoxicillin as the standard empirical outpatient therapy for this population. 1

The high-dose regimen (3 grams total daily) is critical; standard-dose amoxicillin (500 mg three times daily) provides insufficient pneumococcal coverage against resistant strains and should be avoided. 2

Alternative First-Line Option: Doxycycline

Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin cannot be used. 1, 2 Doxycycline provides broad-spectrum coverage including atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) and has demonstrated comparable efficacy to fluoroquinolones in hospitalized patients at significantly lower cost. 1 However, this carries a conditional recommendation with lower quality evidence compared to amoxicillin. 1, 2

Why Macrolides Are NOT First-Line

Macrolide monotherapy (azithromycin or clarithromycin) 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 ranges from 20–30%, making macrolide monotherapy unsafe as first-line therapy. 1, 2 Breakthrough pneumococcal bacteremia occurs significantly more frequently with macrolide-resistant strains, leading to treatment failure. 1, 2

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 This early checkpoint is critical to identify treatment failure before complications develop.

When to Escalate or Refer to Hospital

Indicators of treatment failure requiring escalation include:

• No clinical improvement by day 2–3 1, 2
• Development of respiratory distress (respiratory rate >30/min, oxygen saturation <92% on room air) 1, 2
• Inability to tolerate oral antibiotics (vomiting, GI dysfunction) 1, 2
• New complications such as pleural effusion or sepsis 1, 2

If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) to provide atypical pathogen coverage. 1, 2 If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2

Critical Pitfalls to Avoid

Never use fluoroquinolones as first-line therapy in uncomplicated outpatient CAP. 1, 2 Reserve them for patients with comorbidities or documented treatment failure due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1, 2

Avoid oral cephalosporins (cefuroxime, cefpodoxime) as first-line agents. 1, 2 They demonstrate inferior in-vitro activity compared to high-dose amoxicillin, lack coverage of atypical pathogens, and are more costly without demonstrated clinical superiority. 1, 2

Do not assume all pneumonia requires atypical coverage. 2 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. 2

Follow-Up and Prevention

Schedule a routine follow-up visit at 6 weeks; 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 vaccine to all adults ≥65 years and those with high-risk conditions, and recommend annual influenza vaccination for all patients. 1, 2 Provide smoking-cessation counseling to all current smokers. 1, 2