What is the recommended empiric therapy for an otherwise healthy adult with community‑acquired pneumonia managed as an outpatient, and how should treatment be adjusted if the patient requires hospital admission or intensive‑care unit care?

Treatment of Community-Acquired Pneumonia in Adults

Outpatient Management (Healthy Adults Without Comorbidities)

Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line therapy for previously healthy adults with community-acquired pneumonia, providing superior coverage against 90–95% of Streptococcus pneumoniae isolates including many penicillin-resistant strains. 1

• Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens. 1
• Macrolide monotherapy (azithromycin or clarithromycin) should only be used when local pneumococcal macrolide resistance is documented to be <25%; in most U.S. regions resistance is 20–30%, making this approach unsafe as first-line therapy. 1
• 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; typical duration is 5–7 days. 1

Outpatient Management (Adults With Comorbidities)

For patients with chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancy, asplenia, immunosuppression, or recent antibiotic use within 90 days, combination therapy is required. 1

• Option 1 – Combination therapy: Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin (500 mg day 1, then 250 mg daily for 5–7 days) or doxycycline 100 mg twice daily. 1
• Option 2 – Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days, reserved for patients with β-lactam allergy or when combination therapy is contraindicated due to FDA safety warnings. 1

Hospitalized Patients (Non-ICU)

For hospitalized patients not requiring intensive care, ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily is the preferred regimen, providing coverage for typical bacterial pathogens and atypical organisms with strong evidence and high-quality data. 1

• Alternative β-lactams include 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) is equally effective and reserved for penicillin-allergic patients. 1
• Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1
• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy. 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality in critically ill individuals 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
• For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours plus a respiratory fluoroquinolone. 1

Special Pathogen Coverage (Risk-Based Only)

Pseudomonas aeruginosa 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, prior respiratory isolation of P. aeruginosa, or chronic broad-spectrum antibiotic exposure ≥7 days in the past month. 1

• Regimen: Piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours or carbapenem 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 CAP regimen. 1

Duration of Therapy and Transition to Oral Antibiotics

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

• For uncomplicated CAP, a typical total course is 5–7 days. 1
• Extended courses of 14–21 days are required only for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1
• Switch from IV to oral therapy when the patient is hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm), clinically improving, afebrile for 48–72 hours, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, and able to take oral medication—typically by hospital day 2–3. 1
• Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily. 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients; it fails to cover typical pathogens such as S. pneumoniae and leads to treatment failure. 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1
• Do not add broad-spectrum antipseudomonal or MRSA agents routinely; restrict their use to patients with documented risk factors to prevent unnecessary resistance and adverse effects. 1
• Never delay antibiotic administration beyond 8 hours in hospitalized patients; this increases 30-day mortality by 20–30%. 1

Monitoring and Follow-Up

• Monitor temperature, respiratory rate, pulse, blood pressure, mental status, and oxygen saturation at least twice daily in hospitalized patients. 1, 2
• If no clinical improvement by day 2–3, obtain repeat chest radiograph, inflammatory markers (CRP, white blood cell count), and additional microbiologic specimens to assess for complications such as pleural effusion, empyema, or resistant organisms. 1, 3
• Schedule a routine follow-up visit at 6 weeks; obtain a chest radiograph only if symptoms persist, physical signs remain abnormal, or the patient has high risk for underlying malignancy (smokers >50 years). 1, 2

Prevention

• Offer pneumococcal polysaccharide vaccination to all adults ≥65 years and those with high-risk conditions. 1
• Recommend annual influenza vaccination for all patients. 1
• Provide smoking-cessation counseling to all current smokers. 1