Community-Acquired Pneumonia Treatment in Healthy Adults
For an otherwise healthy adult with community-acquired pneumonia, amoxicillin 1 gram orally three times daily for 5-7 days is the preferred first-line treatment. 1
Outpatient Treatment Algorithm
First-Line Therapy for Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line antibiotic, providing excellent coverage against Streptococcus pneumoniae (the most common pathogen, accounting for 48% of cases) with activity against 90-95% of pneumococcal strains including many with intermediate penicillin resistance 1, 2
Doxycycline 100 mg orally twice daily for 5-7 days serves as an acceptable alternative, offering broad-spectrum coverage including atypical organisms (Mycoplasma, Chlamydophila, Legionella) with comparable efficacy to fluoroquinolones at significantly lower cost 1, 2, 3
Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily for 5-7 days) should ONLY be used when local pneumococcal macrolide resistance is documented to be <25%, as breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains 1, 2
Treatment for Adults With Comorbidities
Comorbidities requiring combination therapy include: chronic heart disease, lung disease (COPD, asthma), liver disease, renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, immunosuppressing conditions/medications, or recent antibiotic use within 90 days 1, 2
Combination therapy: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 (total duration 5-7 days), providing dual coverage against typical bacterial pathogens and atypical organisms with 91.5% favorable clinical outcomes 1, 2
Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily for 5 days OR moxifloxacin 400 mg daily for 5-7 days), which is active against >98% of S. pneumoniae strains including penicillin-resistant isolates, though fluoroquinolones should be reserved due to concerns about resistance development and serious adverse events (tendinopathy, peripheral neuropathy, CNS effects) 1, 2, 4
Treatment Duration
Minimum 5 days of therapy and until afebrile for 48-72 hours with no more than one sign of clinical instability, with typical duration for uncomplicated CAP being 5-7 days 1, 5
Short-course regimens (≤7 days) demonstrate equivalent clinical cure rates with fewer adverse events compared to extended courses (>7 days), with no differences in mortality risk (RR 0.81,95% CI 0.46-1.43) or bacteriologic eradication (RR 1.11,95% CI 0.76-1.62) 5
Extend duration to 14-21 days ONLY if: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli are identified 1, 2
Critical Clinical Pitfalls to Avoid
NEVER use macrolide monotherapy in patients with any comorbidities or in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia 1, 2
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk 1, 2
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendinopathy, peripheral neuropathy, CNS effects) and resistance concerns 1, 2
Broad-spectrum antibiotics (fluoroquinolones, β-lactam + macrolide combinations) are associated with increased risk of adverse drug events including nausea/vomiting/abdominal pain (RD per 1000: 3.20,95% CI 0.99-5.73), non-C. difficile diarrhea (RD per 1000: 4.61,95% CI 2.47-6.82), and vulvovaginal candidiasis (RD per 1000: 3.57,95% CI 0.87-6.88) compared to narrow-spectrum regimens 6
When to Consider Hospitalization
Use PSI (Pneumonia Severity Index) or CURB-65 score to guide site-of-care decisions, with CURB-65 score ≥2 warranting consideration for hospitalization 1, 7
Clinical features requiring hospitalization include: hypoxemia, hemodynamic instability, inability to take oral medications, altered mental status, or failure of outpatient therapy 7