Treatment for Community-Acquired Pneumonia

Outpatient Management – Previously Healthy Adults

Amoxicillin 1 g orally three times daily for 5–7 days is the first-line treatment for healthy adults without comorbidities, providing superior pneumococcal coverage against 90–95% of Streptococcus pneumoniae strains, including many penicillin-resistant isolates. 1

Doxycycline 100 mg orally twice daily serves as an acceptable alternative when amoxicillin is contraindicated, offering broad-spectrum coverage including atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 2
Macrolide monotherapy (azithromycin 500 mg 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%—in most U.S. regions resistance is 20–30%, making monotherapy unsafe as first-line. 1, 2

Outpatient Management – Adults with Comorbidities

For patients with comorbidities (COPD, diabetes, chronic heart/lung/liver/renal disease, alcoholism, malignancy, immunosuppression, or recent antibiotic use within 90 days), combination therapy is mandatory. 1

Preferred regimen: Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg on day 1, then 250 mg daily for 5–7 days total. 1
Alternative β-lactams (cefpodoxime or cefuroxime) can substitute for amoxicillin-clavulanate, always combined with a macrolide or doxycycline 100 mg twice daily. 1
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is an alternative when β-lactams or macrolides are contraindicated, though fluoroquinolones should be reserved due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection). 1, 2

Hospitalized Patients (Non-ICU)

Two equally effective regimens exist with strong recommendations and high-quality evidence: 1

β-lactam plus macrolide combination: Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally 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 azithromycin. 1
Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 1
- Fluoroquinolone monotherapy is reserved for penicillin-allergic patients or when combination therapy is contraindicated. 1

The β-lactam plus macrolide regimen provides comprehensive coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella), achieving 91.5% favorable clinical outcomes. 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with significantly higher mortality in critically ill patients with bacteremic pneumococcal pneumonia. 1

Preferred ICU regimen: Ceftriaxone 2 g IV once 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 or a 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 and β-lactam plus fluoroquinolone. 1

Special Pathogen Coverage (Risk-Based Only)

Antipseudomonal Coverage

Add antipseudomonal therapy only when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of Pseudomonas aeruginosa. 1

Regimen: Piperacillin-tazobactam 4.5 g IV every 6 hours plus ciprofloxacin 400 mg IV every 8 hours (or levofloxacin 750 mg IV daily) plus an aminoglycoside (gentamicin or tobramycin 5–7 mg/kg IV daily) for dual antipseudomonal coverage. 1

MRSA Coverage

Add MRSA therapy only when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1

Regimen: Vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) or linezolid 600 mg IV every 12 hours, added to the base regimen. 1

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. 1

Typical duration for uncomplicated CAP: 5–7 days. 1
Extended duration (14–21 days) is required only for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2

Transition from IV to Oral Therapy

Switch to oral antibiotics when the patient is hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm), clinically improving (afebrile 48–72 hours, respiratory rate ≤24 breaths/min), oxygen saturation ≥90% on room air, able to take oral medication, and has normal GI function—typically by hospital day 2–3. 1

Oral step-down options: amoxicillin 1 g three times daily plus azithromycin 500 mg daily (or azithromycin alone after 2–3 days of IV therapy). 1

Critical Timing and Pitfalls to Avoid

Administer the first antibiotic dose immediately upon diagnosis, ideally in the emergency department—delays beyond 8 hours increase 30-day mortality by 20–30% in hospitalized patients. 1
Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1
Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and is associated with treatment failure. 1
Avoid macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25%—this increases risk of breakthrough bacteremia and treatment failure. 1
Do not add broad-spectrum antipseudomonal or MRSA agents automatically—restrict to patients with documented risk factors to prevent resistance, adverse effects, and unnecessary cost. 1
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and rising resistance. 1

Follow-Up and Monitoring

Outpatient review at 48 hours (or sooner if clinically indicated) to assess symptom resolution, oral intake, and treatment response. 1, 2
Signs of treatment failure warranting hospital referral: no clinical improvement by day 2–3, development of respiratory distress or hypoxemia, inability to tolerate oral antibiotics, or new complications such as pleural effusion. 1
Escalation strategy for outpatient failure: if amoxicillin monotherapy fails, add or substitute a macrolide; if combination therapy fails, switch to a respiratory fluoroquinolone. 1, 2
Routine follow-up at 6 weeks for all patients; chest radiograph only for those with persistent symptoms, abnormal physical findings, or high risk for underlying malignancy (e.g., smokers >50 years). 1

What is the recommended initial antibiotic regimen for an adult with community‑acquired pneumonia, stratified by outpatient status, comorbidities, hospital admission, and intensive‑care unit need?

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