What is the first line treatment for community acquired pneumonia?

First-Line Treatment for Community-Acquired Pneumonia

For outpatients without comorbidities, amoxicillin 1 g three times daily is the preferred first-line treatment, with doxycycline 100 mg twice daily as an acceptable alternative. For outpatients with comorbidities or recent antibiotic use, combination therapy with a β-lactam plus macrolide or respiratory fluoroquinolone monotherapy is recommended. For hospitalized patients, β-lactam plus macrolide combination (such as ceftriaxone 1-2 g daily plus azithromycin 500 mg daily) or respiratory fluoroquinolone monotherapy represents first-line therapy. 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

The American Thoracic Society recommends amoxicillin 1 g orally three times daily as the preferred first-line agent based on moderate quality evidence supporting its effectiveness against common CAP pathogens. 1, 2 This recommendation represents a significant shift from older North American guidelines that favored macrolides, aligning more closely with European approaches that prioritize aminopenicillins to minimize resistance development. 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, 2

• Macrolides (azithromycin 500 mg on 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 This restriction addresses the critical concern that widespread macrolide use has driven resistance rates, and macrolide monotherapy can lead to treatment failure with resistant isolates. 1

Outpatients With Comorbidities or Recent Antibiotic Use

For patients with chronic heart disease, lung disease, diabetes, renal insufficiency, malignancy, or recent antibiotic exposure within 3 months, combination therapy is required. 1, 2

• Combination regimen: β-lactam (amoxicillin-clavulanate 2 g twice daily, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline. 1, 2 High-dose amoxicillin targets ≥93% of S. pneumoniae including drug-resistant strains. 1

• Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily). 1, 2 However, fluoroquinolone use should be discouraged in uncomplicated cases due to concerns about resistance development and increasing FDA warnings regarding serious adverse events. 1

• Critical caveat: If the patient received antibiotics from one class recently, select a different antibiotic class to minimize resistance risk. 1

Inpatient Non-ICU Treatment

For hospitalized patients without ICU-level severity, two equally effective regimens exist with strong recommendations and high-quality evidence. 1, 2

First-Line Regimens (Equal Efficacy)

• β-lactam plus macrolide combination: Ceftriaxone 1-2 g IV daily (or cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 1.5-3 g IV every 6 hours) plus azithromycin 500 mg daily. 1, 2, 3 This combination provides coverage for both typical bacterial pathogens and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1

• Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 1, 2, 4 Systematic reviews demonstrate that fluoroquinolone monotherapy results in fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations, though mortality rates are equivalent. 1

• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative. 1

• β-lactam plus doxycycline 100 mg twice daily represents a third option for patients with contraindications to both macrolides and fluoroquinolones, though this carries conditional recommendation with low-quality evidence. 1, 2, 5

Critical Implementation Points

• Administer the first antibiotic dose in the emergency department immediately upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 2, 3

• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy. 1, 2

• Transition from IV to oral therapy when patients are hemodynamically stable, clinically improving, able to take oral medications, and have normal GI function—typically by day 2-3 of hospitalization. 1, 2

ICU-Level Severe CAP

All ICU patients require mandatory combination therapy with broader coverage. 1, 2

• β-lactam (ceftriaxone 2 g IV daily, cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 3 g IV every 6 hours) plus either azithromycin 500 mg daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1, 2 This strong recommendation is based on retrospective studies demonstrating significant mortality reduction with combination therapy compared to β-lactam monotherapy. 1

Special Populations Requiring Expanded Coverage

Risk Factors for Pseudomonas aeruginosa

Add antipseudomonal coverage when patients have structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1, 2

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, 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) plus azithromycin. 1, 2

Risk Factors for MRSA

Add MRSA coverage for patients with prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1, 2

• 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 the base regimen. 1, 2

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, 2 The typical duration for uncomplicated CAP is 5-7 days. 1, 2, 3

• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 2

• Evidence demonstrates that short-course treatment (≤6 days) achieves equivalent clinical cure rates with fewer adverse events compared to ≥7 days. 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—this leads to treatment failure. 1, 2

• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns. 1

• Do not use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy for standard hospitalized CAP—reserve these for patients with specific risk factors for resistant organisms. 2

• Do not extend therapy beyond 7 days in responding patients without specific indications—this increases antimicrobial resistance risk without clinical benefit. 2

• Avoid delayed antibiotic administration in hospitalized patients—every hour of delay increases mortality risk. 2, 3