In otherwise healthy adults and children with mild‑to‑moderate community‑acquired pneumonia, no recent antibiotic use or risk factors for atypical or resistant pathogens, what is the appropriate first‑line oral antibiotic and its dosing regimen?

Amoxicillin for Community-Acquired Pneumonia: First-Line Oral Therapy

For otherwise healthy adults and children with mild-to-moderate community-acquired pneumonia, amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line antibiotic, providing superior pneumococcal coverage compared to oral cephalosporins and macrolides in most clinical settings. 1

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Outpatient Treatment for Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5–7 days is the gold standard first-line therapy, retaining activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains (MIC ≤2 mg/L). 1, 2
• This regimen covers the most common bacterial pathogen in CAP—S. pneumoniae—which accounts for 50–66% of bacteriologically confirmed cases. 2
• Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin is contraindicated, though it carries lower-quality evidence. 1
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%; in most U.S. regions, resistance ranges from 20–30%, making macrolides unsafe as first-line agents. 1, 2

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Outpatient Treatment for Adults With Comorbidities or Recent Antibiotic Use

• Patients with chronic heart, lung, liver, or renal disease, diabetes, malignancy, or antibiotic use within 90 days require combination therapy to cover both typical and atypical pathogens. 1
• Preferred regimen: Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg on day 1, then 250 mg daily for days 2–5. 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) for 5–7 days, reserved for patients with β-lactam or macrolide contraindications. 1, 3
• The combination approach ensures coverage of β-lactamase-producing organisms (H. influenzae, M. catarrhalis) and atypical pathogens (Mycoplasma, Chlamydophila, Legionella). 1

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Pediatric Dosing for Community-Acquired Pneumonia

• Amoxicillin 90 mg/kg/day divided into two or three doses (maximum 4 g/day) for 5–7 days is first-line therapy for children aged 3 months to 18 years with uncomplicated CAP. 4
• High-dose amoxicillin (90 mg/kg/day) achieves >93% probability of target attainment against pneumococcal isolates, including resistant strains. 5
• Treatment duration should not exceed 7 days in responding patients; shorter 5-day courses are equally effective as 10-day regimens for uncomplicated pneumonia. 6, 4
• For children with comorbidities or severe disease, amoxicillin-clavulanate 90 mg/kg/day (amoxicillin component) divided twice daily provides broader coverage. 4

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Duration of Therapy and Clinical Stability Criteria

• Minimum treatment duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1
• Typical course for uncomplicated CAP: 5–7 days once clinical improvement is documented. 1, 6
• Clinical stability criteria include: 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
• Extended courses (14–21 days) are required only for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1

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When Amoxicillin Monotherapy Is Insufficient

• Add or substitute a macrolide (azithromycin 500 mg day 1, then 250 mg daily) if no clinical improvement by day 2–3 on amoxicillin monotherapy, suggesting atypical pathogen involvement. 1
• Switch to respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) if combination therapy fails or if patient has contraindications to both β-lactams and macrolides. 1
• Hospitalization is indicated if the patient develops respiratory distress (respiratory rate >30/min, oxygen saturation <92%), inability to tolerate oral intake, multilobar infiltrates, or altered mental status. 1

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Critical Pitfalls to Avoid

• Never use oral cephalosporins (cefuroxime, cefpodoxime) as first-line therapy; they demonstrate inferior in-vitro activity compared to high-dose amoxicillin and lack atypical pathogen coverage. 1
• Avoid macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia. 1
• Do not prescribe standard-dose amoxicillin (500 mg three times daily); the high-dose regimen (1 g three times daily) is required to overcome penicillin-resistant strains. 1, 2
• 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. 1
• Do not extend therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes. 1, 6

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Follow-Up and Monitoring

• Clinical review at 48 hours (or sooner if indicated) to assess symptom resolution, oral intake, and treatment response. 1
• Signs of treatment failure warranting hospital referral include: no clinical improvement by day 2–3, development of respiratory distress or hypoxemia, inability to tolerate oral antibiotics, or new complications such as pleural effusion. 1
• Routine follow-up at 6 weeks for all patients; chest radiograph only for those with persistent symptoms, abnormal physical findings, or high risk for underlying malignancy (smokers >50 years). 1

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Special Populations Requiring Alternative Regimens

• Suspected aspiration pneumonia: Amoxicillin-clavulanate 875/125 mg twice daily or clindamycin to ensure anaerobic coverage. 1
• Patients with COPD or asthma: Combination therapy (β-lactam plus macrolide or fluoroquinolone monotherapy) even in the outpatient setting due to increased risk of Pseudomonas aeruginosa and resistant pathogens. 1
• Recent antibiotic exposure (within 90 days): Select an agent from a different class to minimize resistance; if patient recently received β-lactam, use fluoroquinolone or doxycycline. 1