What is the recommended treatment for community-acquired pneumonia (CAP) in a previously healthy adult?

Treatment of Community-Acquired Pneumonia in Previously Healthy Adults

For previously healthy adults with community-acquired pneumonia, amoxicillin 1 gram orally three times daily for 5-7 days is the preferred first-line outpatient therapy, while hospitalized patients require combination therapy with ceftriaxone 1-2 grams IV daily plus azithromycin 500 mg daily. 1

Outpatient Treatment (Previously Healthy Adults Without Comorbidities)

First-Line Therapy:

• Amoxicillin 1 gram orally three times daily for 5-7 days is the preferred regimen based on strong recommendation and moderate-quality evidence 1
• This high-dose regimen provides superior coverage against Streptococcus pneumoniae, including drug-resistant strains, compared to standard dosing 1

Alternative Options:

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though this carries a conditional recommendation with lower quality evidence 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2

Critical Pitfall: Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia 1

Outpatient Treatment (Adults With Comorbidities)

Comorbidities include COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within the past 3 months 1

Combination Therapy (Preferred):

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
• Alternative β-lactams: cefpodoxime or cefuroxime (though less active than high-dose amoxicillin) 1

Fluoroquinolone Monotherapy (Alternative):

• Levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily 1, 3
• However, fluoroquinolone use should be discouraged in uncomplicated cases due to resistance concerns and serious adverse events 1

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong recommendations and high-quality evidence: 1

Option 1: β-lactam Plus Macrolide Combination

• Ceftriaxone 1-2 grams IV daily PLUS azithromycin 500 mg daily 1, 4, 5
• Alternative β-lactams: cefotaxime 1-2 grams IV every 8 hours or ampicillin-sulbactam 3 grams IV every 6 hours 1
• This combination provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1

Option 2: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 1

For Penicillin-Allergic Patients:

• Respiratory fluoroquinolone is the preferred alternative 1
• Alternative: aztreonam 2 grams IV every 8 hours PLUS azithromycin 500 mg IV daily 1

Severe CAP Requiring ICU Admission

Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate for severe disease 1, 5

Preferred Regimen:

• Ceftriaxone 2 grams IV daily (or cefotaxime 1-2 grams IV every 8 hours or ampicillin-sulbactam 3 grams IV every 6 hours) PLUS azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 5

For Penicillin-Allergic ICU Patients:

• Aztreonam 2 grams IV every 8 hours PLUS levofloxacin 750 mg IV daily 1

Special Pathogen Coverage

Add Antipseudomonal Coverage ONLY When Risk Factors Present:

• Risk factors: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa 1
• 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) 1

Add MRSA Coverage ONLY When Risk Factors Present:

• Risk factors: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 1
• Regimen: vancomycin 15 mg/kg IV every 8-12 hours OR linezolid 600 mg IV every 12 hours added to base regimen 1

Duration of Therapy

Standard Duration:

• Minimum of 5 days AND until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1, 5, 6
• Typical duration for uncomplicated CAP is 5-7 days 1, 6
• Recent evidence supports 3-day treatment for patients achieving clinical stability by day 3 6

Extended Duration (14-21 days) Required For:

• Legionella pneumophila 1
• Staphylococcus aureus 1
• Gram-negative enteric bacilli 1

Clinical Stability Criteria:

• 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: 1, 2

• Hemodynamically stable
• Clinically improving
• Afebrile for 48-72 hours
• Able to take oral medications
• Normal gastrointestinal function
• Typically by day 2-3 of hospitalization 1

Oral Step-Down Options:

• Amoxicillin 1 gram orally three times daily 1
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily 1
• Levofloxacin 750 mg orally once daily 3
• Continue azithromycin 500 mg orally daily if part of initial regimen 4

Critical Timing Considerations

Administer the first antibiotic dose IMMEDIATELY upon diagnosis, ideally while still in the emergency department 1, 5

• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 1

Diagnostic Testing for Hospitalized Patients

Obtain BEFORE initiating antibiotics: 1

• Blood cultures (two sets)
• Sputum Gram stain and culture
• Urinary antigen testing for Legionella pneumophila serogroup 1 (in severe CAP or ICU patients)
• COVID-19 and influenza testing when these viruses are common in the community 5

Common Pitfalls to Avoid

• Never use macrolide monotherapy for hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events 1
• Do not automatically add broad-spectrum coverage for Pseudomonas or MRSA without documented risk factors 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1, 6
• Never delay antibiotic administration to obtain cultures—start empiric therapy immediately 1, 5