What is the initial treatment recommendation for a patient diagnosed with pneumonia?

Initial Treatment for Community-Acquired Pneumonia

For outpatient treatment of previously healthy adults without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, while hospitalized non-ICU patients should receive ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, and ICU patients require mandatory combination therapy with ceftriaxone 2 g IV daily plus either azithromycin 500 mg IV daily or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Previously Healthy Adults (No Comorbidities, Age <65)

• First-line: Amoxicillin 1 g orally three times daily for 5-7 days provides optimal coverage against Streptococcus pneumoniae including drug-resistant strains 1, 2
• Alternative: Doxycycline 100 mg orally twice daily for 5-7 days if amoxicillin cannot be tolerated 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented <25% 1, 3

Adults with Comorbidities or Age ≥65

• Combination therapy: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 (total 5-7 days) 1, 2
• Alternative combination: Cefpodoxime or cefuroxime PLUS macrolide or doxycycline 1
• Fluoroquinolone monotherapy: Levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily for 5-7 days 1
• Comorbidities include COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within past 3 months 1

Hospitalized Non-ICU Patients

Standard Regimens (Two Equally Effective Options)

• β-lactam plus macrolide: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily 1, 4
• Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1
• Alternative β-lactams: Cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours (always combined with macrolide) 1

Penicillin-Allergic Patients

• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) is the preferred alternative 1
• Alternative: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg daily 1

Critical Timing Consideration

• Administer the first antibiotic dose in the emergency department immediately upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 4

Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• 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, 4
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 1
• Monotherapy is inadequate for severe disease 1

Special Pathogen Coverage

Add antipseudomonal coverage ONLY when these risk factors are present: 1

• Structural lung disease (bronchiectasis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of Pseudomonas aeruginosa

Antipseudomonal regimen: Piperacillin-tazobactam, cefepime, 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

Add MRSA coverage ONLY when these risk factors are present: 1

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

MRSA 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 base regimen 1

Duration of Therapy

• Minimum 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1, 4
• Typical duration for uncomplicated CAP: 5-7 days 1, 4
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 5, 1
• For severe microbiologically undefined pneumonia: 10 days 5

Transition to Oral Therapy

• Switch from IV to oral when: hemodynamically stable, clinically improving, afebrile for 24 hours, able to take oral medications, normal GI function 5, 1
• Typically occurs by day 2-3 of hospitalization 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, OR continue respiratory fluoroquinolone 1

Essential Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture BEFORE initiating antibiotics in ALL hospitalized patients 1
• Test for COVID-19 and influenza when these viruses are common in the community 4
• Urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—leads to treatment failure 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events 1
• Do not automatically add broad-spectrum antibiotics (antipseudomonal or anti-MRSA coverage) without documented risk factors 1
• Do not extend therapy beyond 7-8 days in responding patients without specific indications—increases antimicrobial resistance risk 1
• If patient received antibiotics within past 90 days, select agent from different antibiotic class 1