What outpatient antibiotic regimen should I prescribe for a healthy adult with community‑acquired pneumonia presenting with mild fever, wheezing, slight leukocytosis, a three‑day history of symptoms, patchy infiltrates on chest X‑ray, and no risk factors for drug‑resistant organisms?

Antibiotic Regimen for Community-Acquired Pneumonia in a Healthy Adult Without Risk Factors

For this previously healthy patient with mild community-acquired pneumonia and no risk factors for drug-resistant organisms, prescribe amoxicillin 1 g orally three times daily for 5–7 days as first-line therapy. 1

Rationale for Amoxicillin as First-Line

• High-dose amoxicillin (3 g per day total) retains in-vitro activity against approximately 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, making it the most effective oral agent for the predominant bacterial pathogen in community-acquired pneumonia. 1
• Both the American Thoracic Society and European respiratory societies endorse amoxicillin as the standard empirical outpatient therapy for previously healthy adults with community-acquired pneumonia. 1
• This patient has no comorbidities (no chronic heart, lung, liver, or renal disease; no diabetes; no immunosuppression) and no recent antibiotic exposure, placing him in the lowest-risk category where narrow-spectrum therapy is appropriate. 2, 1

Alternative First-Line Options

• Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative if amoxicillin is contraindicated, offering coverage of both typical and atypical organisms. 2, 1
• Macrolide monotherapy should be avoided in most U.S. regions because pneumococcal macrolide resistance now ranges from 20–30%, exceeding the 25% threshold where macrolides become unsafe as first-line agents. 2, 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. 2, 1
• The typical total duration for uncomplicated community-acquired pneumonia is 5–7 days. 2, 1
• Schedule a clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 2, 1

When to Escalate or Hospitalize

• Signs of treatment failure requiring 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. 2, 1
• If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to cover atypical pathogens (Mycoplasma, Chlamydophila, Legionella). 2, 1
• If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 2, 1

Critical Pitfalls to Avoid

• Do not use oral cephalosporins (cefuroxime, cefpodoxime) as first-line therapy—they show inferior in-vitro activity compared with high-dose amoxicillin, lack coverage of atypical pathogens, and are more costly without demonstrated clinical superiority. 1
• Do not prescribe macrolide monotherapy (azithromycin or clarithromycin alone) in regions where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia. 2, 1, 3
• Do not use fluoroquinolones as first-line therapy in uncomplicated outpatient pneumonia—reserve them for patients with comorbidities or treatment failure, given FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 2, 1
• Do not assume all pneumonia requires atypical coverage—in previously healthy adults without severe illness, amoxicillin or doxycycline monotherapy provides adequate empiric coverage, and atypical pathogens can be addressed if initial therapy fails. 2, 1

Follow-Up and Prevention

• A routine follow-up at 6 weeks is recommended for all patients; chest radiograph is only needed if symptoms persist, physical signs remain, or the patient is at high risk for underlying malignancy (smokers >50 years). 2, 1
• Offer pneumococcal polysaccharide vaccine to all adults ≥65 years and those with high-risk conditions, and recommend annual influenza vaccination for all patients. 2, 1