What is the recommended treatment for Community-Acquired Pneumonia (CAP) in a patient, considering local resistance patterns and severity of the disease?

Community-Acquired Pneumonia Treatment Guidelines

Outpatient Treatment for Healthy Adults Without Comorbidities

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy for previously healthy outpatients with community-acquired pneumonia. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 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 documented to be <25% 1, 2
• Avoid macrolide monotherapy in areas with high resistance rates to prevent treatment failure 1

Outpatient Treatment for Adults With Comorbidities

For patients with comorbidities (COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use within 3 months), combination therapy is required rather than monotherapy. 1, 3

• Preferred regimen: 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 can be substituted for amoxicillin-clavulanate, always combined with a macrolide or doxycycline 1
• Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily), though fluoroquinolone use should be discouraged in uncomplicated cases due to resistance concerns and serious adverse events 1, 4

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong evidence: β-lactam plus macrolide combination or respiratory fluoroquinolone monotherapy. 1

• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV or oral) 1, 5
• Alternative β-lactams: Cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1
• Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 4
• For penicillin-allergic patients: Respiratory fluoroquinolone is the preferred alternative 1
• Administer the first antibiotic dose in the emergency department immediately upon diagnosis, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1

• Preferred regimen: 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 daily 1, 5
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 4
• For penicillin-allergic ICU patients: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily OR aztreonam PLUS levofloxacin 750 mg IV daily 1

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage ONLY when specific risk factors are present: 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 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1, 4
• For severe cases: Add aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) for dual antipseudomonal coverage 1

MRSA Risk Factors

Add MRSA coverage ONLY when specific risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 1

• 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

Duration of Therapy

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. 1

• Typical duration for uncomplicated CAP: 5-7 days 1
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1
• Avoid extending therapy beyond 7-8 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient meets ALL of the following clinical stability criteria: 1

• Hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 beats/min)
• Clinically improving with temperature ≤37.8°C for 48-72 hours
• Respiratory rate ≤24 breaths/min
• Oxygen saturation ≥90% on room air
• Able to ingest medications with normal gastrointestinal function
• Normal mental status

Typical timing: Day 2-3 of hospitalization 1

Oral step-down options: 1

• Amoxicillin 1 g orally three times daily (preferred oral β-lactam)
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg daily
• Levofloxacin 750 mg orally once daily (for penicillin-allergic patients)
• Doxycycline 100 mg orally twice daily can continue as monotherapy after initial IV β-lactam coverage

Diagnostic Testing for Hospitalized Patients

Obtain blood cultures and sputum Gram stain/culture BEFORE initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and de-escalation 1

• Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—this leads to treatment failure 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns 1, 4
• Do not use oral cephalosporins (cefuroxime, cefpodoxime) as step-down therapy—these have inferior in vitro activity compared to high-dose amoxicillin 1
• Do not automatically add broad-spectrum coverage (antipseudomonal or anti-MRSA) without documented risk factors 1
• Do not delay antibiotic administration—every hour of delay in the first 6 hours increases mortality by 7.6% 1

Follow-Up and Monitoring

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1
• Scheduled clinical review at 6 weeks for all hospitalized patients 1
• Chest radiograph at 6 weeks only for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1
• Chest radiograph NOT required before hospital discharge in patients with satisfactory clinical recovery 1

Prevention Strategies

• Pneumococcal vaccination: Administer 20-valent pneumococcal conjugate vaccine alone OR 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine one year later for all patients ≥65 years and those with high-risk conditions 1
• Annual influenza vaccination for all patients, especially during fall and winter 1
• Smoking cessation should be a goal for all patients hospitalized with CAP who smoke 1