What is the first‑line outpatient treatment for a previously healthy adult with community‑acquired pneumonia who has no recent antibiotic exposure, comorbidities, or risk factors for drug‑resistant organisms?

Treatment for Pneumonia in a Healthy Adult

For a previously healthy adult with community-acquired pneumonia (CAP) who has no recent antibiotic exposure, comorbidities, or risk factors for drug-resistant organisms, amoxicillin 1 g orally three times daily for 5–7 days is the recommended first-line outpatient therapy. 1

First-Line Antibiotic Selection

• Amoxicillin 1 g three times daily is the preferred empiric regimen because it retains in-vitro activity against approximately 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, and provides superior pneumococcal coverage compared with oral cephalosporins. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, offering coverage of both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1

When to Avoid Macrolides

• Macrolide monotherapy (azithromycin or clarithromycin) should only be used when local pneumococcal macrolide resistance is documented to be <25%. 1

• In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, making macrolide monotherapy unsafe as first-line therapy in previously healthy adults. 1

• Macrolides should be reserved for areas with confirmed low resistance to prevent treatment failure and breakthrough bacteremia with resistant strains. 1

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

• The typical total duration for uncomplicated CAP is 5–7 days. 1

• Arrange a clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1

Criteria for Treatment Failure and Escalation

• If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to provide coverage for atypical pathogens. 1

• 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

• If combination therapy (β-lactam plus macrolide/doxycycline) fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1

Agents to Avoid in This Population

• Oral cephalosporins (cefuroxime, cefpodoxime) should not be used as first-line therapy because 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

• Fluoroquinolones should not be used as first-line agents in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance; they are reserved for patients with comorbidities or documented treatment failure. 1

Follow-Up and Prevention

• Routine follow-up should occur 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

• Offer pneumococcal polysaccharide vaccination to all adults ≥65 years and those with high-risk conditions. 1

• Recommend annual influenza vaccination for all patients. 1

• Provide smoking-cessation counseling to every current smoker. 1

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. 1

• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient pneumonia because of safety warnings and resistance concerns. 1

• Do not assume that 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