Antibiotic Dosing for Non-Severe Community-Acquired Pneumonia in Healthy Adults

For an otherwise healthy adult outpatient with non-severe community-acquired pneumonia, normal renal function, and no drug allergies, prescribe amoxicillin 1 gram orally three times daily for 5–7 days as first-line therapy. 1, 2

First-Line Regimen: Amoxicillin Monotherapy

Amoxicillin 1 g orally three times daily for 5–7 days is the preferred empiric treatment for previously healthy adults without comorbidities, supported by strong recommendation and moderate-quality evidence. 1, 2, 3
This regimen provides 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
Amoxicillin is superior to oral cephalosporins in pneumococcal coverage, has an excellent safety profile, and is cost-effective. 1, 2

Alternative Regimens (When Amoxicillin Is Not Suitable)

Doxycycline

Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin is contraindicated or not tolerated. 1, 2, 3
Doxycycline provides broad-spectrum coverage including atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) and typical bacterial pathogens. 1, 3
This carries a conditional recommendation with lower-quality evidence compared to amoxicillin. 1, 2

Macrolide Monotherapy (Restricted Use)

Azithromycin 500 mg on day 1, then 250 mg daily for days 2–5 or clarithromycin 500 mg twice daily should be used only when local pneumococcal macrolide resistance is documented to be <25%. 1, 2, 3, 4
In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, making macrolide monotherapy unsafe as first-line therapy. 1, 2, 3
Macrolide monotherapy in areas with ≥25% resistance leads to breakthrough pneumococcal bacteremia and treatment failure. 1, 2

Treatment Duration and Monitoring

Minimum duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1, 2, 3
Standard course: 5–7 days for uncomplicated CAP in previously healthy adults. 1, 2, 3
Extended courses (14–21 days) are reserved only for infections caused by Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli. 1, 2, 3

Clinical Stability Criteria

Temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, oxygen saturation ≥90% on room air, ability to maintain oral intake, and normal mental status. 1

Follow-Up Assessment

Clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1, 2, 3
Fever should resolve within 2–3 days of appropriate antibiotic therapy. 3

When to Escalate Therapy

Indicators of Treatment Failure Requiring Hospitalization

No clinical improvement by day 2–3 despite appropriate antibiotics. 1, 2
Development of respiratory distress (respiratory rate >30/min, oxygen saturation <92% on room air). 1, 2
Inability to tolerate oral antibiotics due to vomiting or gastrointestinal dysfunction. 1, 2
New complications such as pleural effusion, hypotension, or altered mental status. 1, 2

Escalation Strategy for Amoxicillin Failure

If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to cover atypical pathogens. 1, 2, 3
If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2, 3

Critical Pitfalls to Avoid

Never use macrolide monotherapy in regions where pneumococcal macrolide resistance exceeds 25% (most of the United States), as this leads to treatment failure and breakthrough bacteremia. 1, 2, 3
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance; reserve fluoroquinolones for patients with comorbidities or treatment failure. 1, 2, 3
Do not use oral cephalosporins (cefuroxime, cefpodoxime) as first-line agents because they have inferior in-vitro activity against S. pneumoniae compared to high-dose amoxicillin, lack atypical coverage, and are more costly without demonstrated clinical superiority. 1, 2
Do not automatically extend antibiotic duration beyond 5–7 days in patients who are clinically improving; reassess at day 2–3 rather than prolonging therapy unnecessarily. 1, 2, 3
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2

Preventive Measures

Pneumococcal vaccination: Offer the 20-valent pneumococcal conjugate vaccine alone or the 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine one year later to all adults ≥65 years or those 19–64 years with underlying conditions. 1, 5
Annual influenza vaccination for all patients, especially those with chronic medical illnesses. 1, 5
Smoking cessation counseling for all current smokers. 1

Summary Algorithm

Confirm diagnosis of non-severe CAP in a previously healthy adult without comorbidities.
Prescribe amoxicillin 1 g orally three times daily for 5–7 days as first-line therapy. 1, 2
Alternative: doxycycline 100 mg twice daily if amoxicillin is contraindicated. 1, 2
Avoid macrolide monotherapy unless local resistance is <25%. 1, 2
Assess clinical response at 48 hours; fever should resolve within 2–3 days. 1, 3
If no improvement by day 2–3, add a macrolide or switch to a fluoroquinolone; consider hospitalization if respiratory distress, hypotension, or inability to tolerate oral intake develops. 1, 2
Treat for minimum 5 days and until afebrile 48–72 hours with clinical stability; typical course is 5–7 days. 1, 2

What is the recommended empiric antibiotic choice and dosing for an otherwise healthy adult outpatient with non‑severe community‑acquired pneumonia, normal renal function, and no drug allergies?

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