What is the recommended treatment for community-acquired pneumonia (CAP)?

Community-Acquired Pneumonia Treatment

First-Line Empiric Therapy by Clinical Setting

For previously healthy outpatients without comorbidities, amoxicillin 1 g three times daily is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 1

Outpatient Treatment

Healthy patients without comorbidities:

• Amoxicillin 1 g orally three times daily (preferred, strong recommendation, moderate quality evidence) 1
• Doxycycline 100 mg orally twice daily (acceptable alternative, conditional recommendation) 1
• 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 <25% 1

Patients with comorbidities or recent antibiotic use:

• β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline (strong recommendation) 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) 1

Inpatient Non-ICU Treatment

For hospitalized patients without risk factors for resistant pathogens, β-lactam plus macrolide combination therapy is strongly recommended:

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV/PO daily (strong recommendation, high quality evidence) 1, 2
• Alternative: Cefotaxime 1-2 g IV every 8 hours PLUS azithromycin 500 mg IV/PO daily 1
• Alternative: Ampicillin-sulbactam 3 g IV every 6 hours PLUS azithromycin 500 mg IV/PO daily 1

Alternative monotherapy regimen:

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) (strong recommendation, high quality evidence) 1

The British Thoracic Society recommends combined therapy with amoxicillin and a macrolide for patients requiring hospital admission, though the American guidelines favor third-generation cephalosporins for broader coverage 3, 1.

ICU Treatment for Severe CAP

For patients requiring ICU admission, mandatory combination therapy with β-lactam PLUS either azithromycin OR respiratory fluoroquinolone is required:

• Ceftriaxone 2 g IV daily OR cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours PLUS azithromycin 500 mg IV/PO daily 1
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 1

This dual coverage is essential because ICU patients have higher rates of atypical pathogens and require coverage for both typical bacterial pathogens and organisms like Legionella 1.

Special Considerations for Resistant Pathogens

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage if the patient has:

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

Recommended 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

MRSA Risk Factors

Add MRSA coverage if the patient has:

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

Recommended addition:

• Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 1

Duration of Therapy

Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than 1 sign of clinical instability (strong recommendation) 3, 1.

Standard duration: 5-7 days for uncomplicated CAP 1

Extended duration (14-21 days) required for:

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

The evidence strongly supports shorter courses than historically used, as extending therapy beyond 7 days in responding patients increases antimicrobial resistance risk without improving outcomes 1.

Transition from IV to Oral Therapy

Switch to oral antibiotics when the patient meets ALL of the following criteria:

• Hemodynamically stable 3, 1
• Clinically improving 3, 1
• Able to take oral medications 1
• Normal gastrointestinal function 1

This typically occurs by day 2-3 of hospitalization 1. The tissue half-life of azithromycin allows for continued antimicrobial effect even after oral transition 1.

Recommended oral step-down regimens:

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• Alternative: Amoxicillin 1 g orally three times daily PLUS clarithromycin 500 mg orally twice daily 1
• Respiratory fluoroquinolone continuation (levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily) 1

Critical Pitfalls to Avoid

Timing of first antibiotic dose:

• Administer the first antibiotic dose while still in the emergency department for hospitalized patients, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Macrolide resistance:

• Avoid macrolide monotherapy in areas with >25% pneumococcal macrolide resistance 1
• Never use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for S. pneumoniae 1

Inappropriate β-lactam selection:

• Do not use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
• Third-generation cephalosporins (ceftriaxone, cefotaxime) are preferred for their superior outcomes 1

Overuse of broad-spectrum antibiotics:

• Do not automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors 1
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow targeted de-escalation 1

Pathogen-Directed Therapy

Once the etiology of CAP has been identified using reliable microbiological methods, antimicrobial therapy should be directed at that specific pathogen 3. This allows for de-escalation from empiric broad-spectrum coverage and reduces the risk of antimicrobial resistance 1.

Follow-Up

Clinical review should be arranged for all patients at approximately 6 weeks, either with their general practitioner or in a hospital clinic 3. Chest radiograph at 6 weeks is reserved for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1.