What are the recommended antibiotic regimens for community-acquired pneumonitis?

Antibiotic Treatment for Community-Acquired Pneumonia

For outpatient treatment of previously healthy adults without comorbidities, use amoxicillin 1 gram three times daily for 5-7 days as first-line therapy, with doxycycline 100 mg twice daily as the preferred alternative. 1, 2, 3

Outpatient Treatment Algorithm

Previously Healthy Adults (No Comorbidities)

First-line options:

• Amoxicillin 1 gram orally three times daily for 5-7 days (strong recommendation, moderate quality evidence) 4, 1, 3
• Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 4, 1, 2

Macrolide monotherapy (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 to be <25%. 4, 1, 2 In regions with ≥25% macrolide resistance, avoid macrolide monotherapy entirely. 4

Adults With Comorbidities

Comorbidities include: chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, immunosuppression, or recent antibiotic use within 90 days. 4

Combination therapy (preferred):

• High-dose amoxicillin-clavulanate 2 grams/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days (strong recommendation, moderate quality evidence) 4, 1, 3
• Alternative β-lactams: ceftriaxone, cefpodoxime, or cefuroxime 500 mg twice daily 4
• Doxycycline 100 mg twice daily can substitute for the macrolide 4, 1

Fluoroquinolone monotherapy (alternative):

• Levofloxacin 750 mg orally once daily for 5 days 4, 1, 2
• Moxifloxacin 400 mg orally once daily for 5 days 4, 2
• Gemifloxacin 320 mg orally once daily for 5 days 4, 2

Inpatient Non-ICU Treatment

Two equally effective regimens with strong evidence:

Option 1: Combination therapy (β-lactam + macrolide)

• Ceftriaxone 1-2 grams IV daily PLUS azithromycin 500 mg IV/oral daily (strong recommendation, level I evidence) 4, 2, 3
• Alternative β-lactams: cefotaxime 1-2 grams IV every 8 hours, ampicillin-sulbactam 3 grams IV every 6 hours, or ampicillin 4, 2
• Clarithromycin 500 mg twice daily can substitute for azithromycin 3
• Doxycycline 100 mg twice daily is an alternative to macrolides (level III evidence) 4, 3

Option 2: Fluoroquinolone monotherapy

• Levofloxacin 750 mg IV daily (strong recommendation, level I evidence) 4, 2, 3
• Moxifloxacin 400 mg IV daily (strong recommendation, level I evidence) 4, 2, 3

A 2023 meta-analysis of 18 randomized controlled trials (4,140 participants) demonstrated that respiratory fluoroquinolone monotherapy achieved significantly higher clinical cure rates (86.5% vs 81.5%; OR 1.47) and microbiological eradication rates (86.0% vs 81.0%; OR 1.51) compared to β-lactam plus macrolide combination therapy, with similar mortality and adverse event rates. 5

For penicillin-allergic patients, use respiratory fluoroquinolone monotherapy. 4, 3

Inpatient ICU Treatment (Severe CAP)

Mandatory combination therapy for all ICU patients:

Standard regimen:

• β-lactam (ceftriaxone 2 grams IV daily, cefotaxime 1-2 grams IV every 8 hours, or ampicillin-sulbactam 3 grams 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) (strong recommendation, level I-II evidence) 4, 2, 3

For Pseudomonas aeruginosa risk factors (structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation):

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 grams IV every 6 hours, cefepime 2 grams IV every 8 hours, imipenem 500 mg IV every 6 hours, or meropenem 1 gram IV every 8 hours) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily (moderate recommendation, level III evidence) 4, 2, 3
• Alternative: antipseudomonal β-lactam PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 4, 2

For MRSA risk factors (post-influenza pneumonia, cavitary infiltrates, prior MRSA infection/colonization, recent hospitalization with IV antibiotics):

• 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 (moderate recommendation, level III evidence) 4, 2, 3

For penicillin-allergic ICU patients, use respiratory fluoroquinolone PLUS aztreonam 2 grams IV every 8 hours. 4, 2

Duration of Therapy

Treat for a minimum of 5 days and continue until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability. 2, 3 Standard duration is 5-7 days for uncomplicated CAP. 1, 2, 3

Extend duration to 14-21 days ONLY for:

• Legionella pneumophila infection 1, 2, 3
• Staphylococcus aureus pneumonia 1, 2, 3
• Gram-negative enteric bacilli 1, 2, 3

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient meets ALL criteria:

• Hemodynamically stable 2, 3
• Clinically improving 2, 3
• Able to take oral medications 2, 3
• Normal gastrointestinal function 2, 3

This typically occurs by day 2-3 of hospitalization. 3

Oral step-down regimens:

• Amoxicillin 1 gram orally three times daily PLUS azithromycin 500 mg orally daily 3
• Levofloxacin 750 mg orally daily 2, 3
• Moxifloxacin 400 mg orally daily 2, 3

Critical Pitfalls to Avoid

Delayed antibiotic administration: Administer the first antibiotic dose in the emergency department for all hospitalized patients, as delays beyond 8 hours increase 30-day mortality by 20-30%. 2, 3

Inappropriate macrolide monotherapy: Never use macrolide monotherapy in patients with comorbidities, areas with ≥25% pneumococcal macrolide resistance, recent antibiotic exposure, or hospitalized patients, as breakthrough pneumococcal bacteremia is significantly more common. 4, 1, 3

Recent antibiotic exposure: If the patient received antibiotics within 90 days, select a different antibiotic class to reduce resistance risk. 4, 1, 2

Excessive treatment duration: Do not extend therapy beyond 7 days in responding patients without specific indications (Legionella, S. aureus, gram-negative enteric bacilli), as this increases antimicrobial resistance risk. 2, 3

Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 2, 3