What is the recommended treatment for community-acquired pneumonia in a general adult population?

Treatment for Community-Acquired Pneumonia

For outpatient adults without comorbidities, use amoxicillin 1 g orally three times daily for 5-7 days; for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; and for ICU patients, mandatory combination therapy with ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily is required. 1

Outpatient Treatment

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing excellent coverage against Streptococcus pneumoniae including drug-resistant strains, with strong recommendation and moderate-quality evidence. 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, 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 in areas where pneumococcal macrolide resistance is documented <25%, as higher resistance rates lead to treatment failure. 1

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

• Use combination therapy with a β-lactam plus macrolide OR respiratory fluoroquinolone monotherapy. 1
• Preferred combination: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5, for total duration 5-7 days. 1
• Alternative β-lactams include cefpodoxime or cefuroxime, always combined with a macrolide or doxycycline. 1
• Fluoroquinolone monotherapy option: Levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily for 5-7 days, though this should be reserved for penicillin-allergic patients due to resistance concerns and FDA warnings about serious adverse events. 1

Inpatient Treatment (Non-ICU)

Standard Regimens

• Two equally effective regimens exist with strong recommendations and high-quality evidence: β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy. 1
• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily, providing coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1
• 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, with systematic reviews demonstrating fewer clinical failures compared to β-lactam/macrolide combinations. 1

Penicillin-Allergic Patients

• Use respiratory fluoroquinolone (levofloxacin or moxifloxacin) as the preferred alternative. 1
• If fluoroquinolone contraindicated: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily. 1

Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate and associated with higher mortality. 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
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily). 1
• A 2025 network meta-analysis of 8,142 patients demonstrated that β-lactam plus macrolide was the most effective regimen, significantly reducing overall mortality compared to β-lactam monotherapy. 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, 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 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, cavitary infiltrates on imaging. 1
• Regimen: Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours added to base regimen. 1

Duration of Therapy

• Minimum 5 days AND until 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 specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 2, 1
• For severe microbiologically undefined pneumonia: 10 days of treatment. 2

Transition from IV to Oral Therapy

Switch when ALL criteria met:

• Hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm). 1
• Clinically improving with temperature ≤37.8°C for 24-48 hours. 1
• Respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air. 1
• Able to ingest medications with normal gastrointestinal function. 1
• Typically occurs by day 2-3 of hospitalization. 1

Oral step-down options:

• Amoxicillin 1 g orally three times daily (preferred oral β-lactam). 1
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg orally daily. 1
• Levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily. 1

Critical Timing Considerations

• Administer the first antibiotic dose IMMEDIATELY upon diagnosis, ideally in the emergency department before hospital admission, as delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1, 3
• Each hour of delay in the first 6 hours increases mortality by 7.6%. 1

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

Management of Treatment Failure

If no clinical improvement by day 2-3:

• Obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens. 2
• Consider chest CT to evaluate for complications (pleural effusions, lung abscess, central airway obstruction). 1
• For non-severe pneumonia initially treated with amoxicillin monotherapy: Add or substitute a macrolide. 2
• For non-severe pneumonia on combination therapy: Switch to respiratory fluoroquinolone. 2
• For severe pneumonia not responding to combination therapy: Consider adding rifampicin. 2

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%, as this leads to treatment failure and breakthrough bacteremia. 1
• Do not add antipseudomonal or MRSA coverage empirically without documented risk factors—this promotes resistance without improving outcomes. 1
• Do not extend therapy beyond 7-8 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk. 1
• Do not use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—they have inferior in vitro activity compared to high-dose amoxicillin. 1
• Do not delay switching to oral therapy in stable patients—prolonged IV therapy increases costs and complications without improving outcomes. 3