What is the standard treatment for Community-Acquired Pneumonia (CAP)?

Standard Treatment for Community-Acquired Pneumonia (CAP)

For hospitalized patients without risk factors for resistant bacteria, treat with combination β-lactam plus macrolide therapy (ceftriaxone 1-2g IV daily plus azithromycin 500mg daily) for a minimum of 5 days, with respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily or moxifloxacin 400mg daily) as an equally effective alternative. 1

Outpatient Treatment

Healthy Adults Without Comorbidities

• Amoxicillin 1g three times daily is the preferred first-line therapy, providing excellent coverage against Streptococcus pneumoniae and other typical bacterial pathogens 1
• Doxycycline 100mg twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 1
• Avoid macrolide monotherapy (azithromycin or clarithromycin) in areas where pneumococcal macrolide resistance exceeds 25%, as treatment failure rates increase significantly 1

Adults With Comorbidities

• Combination therapy with β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline is recommended 1
• Alternatively, respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily, moxifloxacin 400mg daily, or gemifloxacin 320mg daily) provides equivalent efficacy 1

Inpatient Non-ICU Treatment

Two regimens have equally strong evidence and should be selected based on patient-specific factors:

First-Line Regimen (Preferred)

• Ceftriaxone 1-2g IV daily plus azithromycin 500mg IV/oral daily provides coverage for both typical and atypical pathogens with strong recommendation and high-quality evidence 1, 2
• Alternative β-lactams include cefotaxime 1-2g IV every 8 hours or ampicillin-sulbactam 3g IV every 6 hours 1
• Clarithromycin 500mg twice daily can substitute for azithromycin 3

Alternative Regimen (Equally Effective)

• Respiratory fluoroquinolone monotherapy with levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily 1, 4
• This regimen is particularly useful for penicillin-allergic patients or when concerns exist about Clostridioides difficile infection 3

Critical Timing Consideration

• Administer the first antibiotic dose in the emergency department before hospital admission, as delays beyond 8 hours increase 30-day mortality by 20-30% 1

ICU Treatment for Severe CAP

Combination therapy is mandatory for all ICU patients:

Standard ICU Regimen

• β-lactam (ceftriaxone 2g IV daily, cefotaxime 1-2g IV every 8 hours, or ampicillin-sulbactam 3g IV every 6 hours) PLUS either azithromycin 500mg daily OR respiratory fluoroquinolone (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) 3, 1
• This dual coverage addresses both typical bacterial pathogens and atypical organisms 1

Risk Factors Requiring Expanded Coverage

For Pseudomonas aeruginosa (if structural lung disease, recent hospitalization with IV antibiotics within 90 days, or prior P. aeruginosa isolation):

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5g IV every 6 hours, cefepime 2g IV every 8 hours, imipenem 500mg IV every 6 hours, or meropenem 1g IV every 8 hours) 3, 1
• PLUS ciprofloxacin 400mg IV every 8 hours OR levofloxacin 750mg IV daily 3, 1
• PLUS aminoglycoside (gentamicin or tobramycin 5-7mg/kg IV daily) for three-drug regimen 3

For MRSA (if post-influenza pneumonia, cavitary infiltrates, prior MRSA infection/colonization, or recent hospitalization with IV antibiotics):

• Add vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20mg/mL) OR linezolid 600mg IV every 12 hours to the base regimen 3, 1

Duration of Therapy

• Treat for a minimum of 5 days and continue until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1
• For uncomplicated CAP, 5-7 days total duration is appropriate once clinical stability is achieved 3, 1
• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 3, 1

Transition to Oral Therapy

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

• Hemodynamically stable (no vasopressor requirement) 1
• Clinically improving (decreased fever, respiratory rate, heart rate) 1
• Able to ingest oral medications 1
• Normal gastrointestinal function 1

This transition typically occurs by day 2-3 of hospitalization and facilitates early discharge without increasing complications or mortality 1, 5

Recommended Oral Step-Down Regimens

• Amoxicillin 1g orally three times daily plus azithromycin 500mg orally daily (or clarithromycin 500mg orally twice daily) 3
• Alternatively, continue the same respiratory fluoroquinolone orally if initially used IV 1

Diagnostic Testing

• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and appropriate de-escalation 1
• Test all patients for COVID-19 and influenza when these viruses are circulating in the community, as positive results may alter treatment strategies 2

Follow-Up and Monitoring

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 3
• Schedule clinical review at 6 weeks for all hospitalized patients, with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 3, 1
• Chest radiograph need not be repeated prior to hospital discharge in patients with satisfactory clinical recovery 3

Critical Pitfalls to Avoid

• Never use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 3
• Avoid cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present, as these agents have inferior outcomes compared to ceftriaxone/cefotaxime 1
• Do not automatically escalate to broad-spectrum antibiotics based solely on comorbidities or immunosuppression without documented risk factors for resistant organisms 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications (such as Legionella, S. aureus, or Gram-negative bacilli), as this increases antimicrobial resistance risk 3, 1