What is the appropriate treatment for community-acquired pneumonia (CAP) in previously healthy adults?

Treatment of Community-Acquired Pneumonia in Previously Healthy Adults

For previously healthy adults with community-acquired pneumonia treated as outpatients, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

First-line therapy:

• Amoxicillin 1 g orally three times daily is the preferred agent based on strong recommendation and moderate-quality evidence, providing excellent coverage against Streptococcus pneumoniae (including drug-resistant strains), Haemophilus influenzae, and Moraxella catarrhalis 1, 2
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though this carries a conditional recommendation with lower quality evidence 1, 2

Macrolide considerations:

• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used in areas where pneumococcal macrolide resistance is documented to be <25% 1, 2
• In areas with higher resistance rates, macrolide monotherapy leads to treatment failure and should be avoided 1

Adults With Comorbidities (COPD, Diabetes, Heart Disease, Renal Disease, Malignancy)

Combination therapy is required:

• β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 1, 2
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 2

Inpatient Treatment Algorithm

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong recommendations:

1. β-lactam plus macrolide combination:

   • Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (strong recommendation, high-quality evidence) 1, 2, 3
   • Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1

2. Respiratory fluoroquinolone monotherapy:

   • Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily (strong recommendation, high-quality evidence) 1, 2

For penicillin-allergic patients: Use respiratory fluoroquinolone as the preferred alternative 1, 2

Severe CAP Requiring ICU Admission

Combination therapy is MANDATORY for all ICU patients:

• β-lactam (ceftriaxone 2 g IV daily, cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 3 g IV every 6 hours) PLUS either azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2
• Monotherapy is inadequate for severe disease and should never be used 1

Duration of Therapy

Standard duration:

• Treat for a minimum of 5 days AND until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 2, 1
• Typical duration for uncomplicated CAP is 5-7 days 2

Extended duration (14-21 days) required for:

• Legionella pneumophila 2
• Staphylococcus aureus 2
• Gram-negative enteric bacilli 2

Clinical stability criteria before discontinuation:

• Temperature ≤37.8°C 1
• Heart rate ≤100 beats/min 1
• Respiratory rate ≤24 breaths/min 1
• Systolic blood pressure ≥90 mmHg 1
• Oxygen saturation ≥90% on room air 1
• Ability to maintain oral intake 1
• Normal mental status 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when:

• Patient is hemodynamically stable 1, 2
• Clinically improving 1, 2
• Able to take oral medications 1, 2
• Normal gastrointestinal function 1, 2
• Typically by day 2-3 of hospitalization 1, 2

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage ONLY when these risk factors are present:

• Structural lung disease (bronchiectasis) 1, 2
• Recent hospitalization with IV antibiotics within 90 days 1, 2
• Prior respiratory isolation of P. aeruginosa 1, 2

Antipseudomonal regimen:

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 1, 2

MRSA Risk Factors

Add MRSA coverage ONLY when these risk factors are present:

• Prior MRSA infection or colonization 1, 2
• Recent hospitalization with IV antibiotics 1, 2
• Post-influenza pneumonia 1, 2
• Cavitary infiltrates on imaging 1, 2

MRSA regimen:

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours to the base regimen 1, 2

Critical Pitfalls to Avoid

1. NEVER delay antibiotic administration beyond 8 hours in hospitalized patients — this increases 30-day mortality by 20-30% 1, 2

2. NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% — this leads to treatment failure 1, 2

3. NEVER use macrolide monotherapy for hospitalized patients — it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1

4. NEVER use azithromycin in patients requiring hospitalization, elderly or debilitated patients, or those with significant underlying health problems — per FDA labeling, azithromycin should not be used in these populations 4

5. NEVER extend therapy beyond 7-8 days in responding patients without specific indications — longer courses increase antimicrobial resistance risk without improving outcomes 1

6. NEVER add antipseudomonal or MRSA coverage without documented risk factors — this promotes resistance and exposes patients to unnecessary adverse effects 1

7. Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients — this allows pathogen-directed therapy and de-escalation 1, 2

8. Administer the first antibiotic dose in the emergency department immediately upon diagnosis — delayed administration is associated with increased mortality 1, 2