What is the first line treatment for an adult patient with community acquired pneumonia?

First-Line Treatment for Community-Acquired Pneumonia in Adults

For outpatients without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 1 For hospitalized non-ICU patients, ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily is the standard regimen, with respiratory fluoroquinolone monotherapy (levofloxacin 750 mg or moxifloxacin 400 mg daily) as an equally effective alternative. 1, 2

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily is the preferred first-line agent based on its effectiveness against common CAP pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries 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 resistance rates exceeding this threshold lead to treatment failure. 1, 3

Adults With Comorbidities or Recent Antibiotic Use

• Combination therapy is mandatory: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline. 1
• Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily), though fluoroquinolone use should be reserved for specific situations due to FDA warnings about serious adverse events. 1
• Comorbidities requiring combination therapy include COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within the past 3 months. 3

Inpatient Treatment Algorithm

Hospitalized Non-ICU Patients

• Two equally effective regimens exist with strong evidence: 1
  • β-lactam plus macrolide: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV or oral). 1, 2
  • Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily. 1, 4
• Alternative β-lactams include cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with a macrolide. 1
• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative. 1
• The first antibiotic dose MUST be administered in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1, 2

Severe CAP Requiring ICU Admission

• Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate for severe disease. 1
• Preferred regimen: 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 IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1, 3
• For penicillin-allergic ICU patients: Respiratory fluoroquinolone PLUS aztreonam 2 g IV every 8 hours. 1

Special Populations Requiring Broader Coverage

Risk Factors for Pseudomonas aeruginosa

• Add antipseudomonal coverage if the patient has: 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, 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

Risk Factors for MRSA

• Add MRSA coverage if the patient has: 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 and Transition to Oral Treatment

• 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. 3, 1, 5
• Typical duration for uncomplicated CAP is 5-7 days—extending therapy beyond 7 days in responding patients increases antimicrobial resistance risk without improving outcomes. 1, 5
• Extended duration (14-21 days) is required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 3, 1
• Switch from IV to oral therapy when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 3, 1
• Oral step-down options: Amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily, or amoxicillin-clavulanate 875/125 mg twice daily PLUS azithromycin. 1

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as macrolide-resistant S. pneumoniae may also be resistant to doxycycline, leading to treatment failure. 1
• NEVER use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and resistance concerns. 1
• Do NOT automatically escalate to broad-spectrum antibiotics (antipseudomonal or anti-MRSA coverage) without documented risk factors, as this increases resistance without improving outcomes. 1
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 1
• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present. 1

Diagnostic Testing Recommendations

• All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment and infection prevention strategies. 2
• Blood cultures and sputum Gram stain/culture should be obtained before initiating antibiotics in all hospitalized patients. 1
• Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients. 1