What is the recommended antibiotic treatment for a patient with community-acquired pneumonia (CAP), considering factors such as severity of illness, medical history, and potential underlying conditions like chronic obstructive pulmonary disease (COPD) or immunocompromised states?

Antibiotic Treatment for Community-Acquired Pneumonia

First-Line Therapy by Clinical Setting

For healthy outpatients without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line antibiotic, with doxycycline 100 mg twice daily as the best alternative. 1, 2, 3

Outpatient Treatment Algorithm

Healthy adults without comorbidities:

• First choice: Amoxicillin 1 g orally three times daily for 5-7 days 1, 3
• Alternative: Doxycycline 100 mg orally twice daily for 5-7 days (consider 200 mg loading dose) 1, 3
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5): ONLY use if local pneumococcal macrolide resistance is documented <25% 1, 2, 4

Adults with comorbidities (COPD, diabetes, heart/liver/renal disease, age ≥65):

• Combination therapy: Amoxicillin-clavulanate 875/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days total 1, 2
• Alternative monotherapy: Levofloxacin 750 mg once daily for 5 days OR moxifloxacin 400 mg once daily for 5 days 1, 2

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong evidence: 1

1. β-lactam plus macrolide: Ceftriaxone 1-2 g IV once daily PLUS azithromycin 500 mg daily 1, 5
2. Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2

For penicillin-allergic patients: Use respiratory fluoroquinolone monotherapy 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1

• Preferred regimen: Ceftriaxone 2 g IV once daily PLUS azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 5
• Alternative β-lactams: Cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours 1

Special Populations Requiring Broader Coverage

Pseudomonas Risk Factors

Add antipseudomonal coverage if patient has: 1

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

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin OR levofloxacin PLUS aminoglycoside (gentamicin or tobramycin) 1

MRSA Risk Factors

Add MRSA coverage if patient has: 1

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

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

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. 1, 5

• Uncomplicated CAP: 5-7 days total 1, 3
• Legionella, S. aureus, or Gram-negative enteric bacilli: Extend to 14-21 days 1, 2

Clinical stability criteria before discontinuation: 1

• Afebrile >48 hours
• Heart rate <100 bpm
• Respiratory rate <24 breaths/min
• Systolic blood pressure >90 mmHg
• Oxygen saturation >90% on room air
• Able to take oral medications

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient is: 1

• Hemodynamically stable
• Clinically improving
• Able to ingest medications
• Has normal GI function

This typically occurs by day 2-3 of hospitalization. 1

Oral step-down options: 1

• Amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily
• Levofloxacin 750 mg once daily
• Moxifloxacin 400 mg once daily

Critical Pitfalls to Avoid

Never use macrolide monotherapy in: 1, 3

• Areas where pneumococcal macrolide resistance ≥25%
• Patients with any comorbidities
• Hospitalized patients (provides inadequate coverage for typical bacterial pathogens)

Never delay antibiotic administration beyond 8 hours in hospitalized patients—this increases 30-day mortality by 20-30%. 1

Administer the first antibiotic dose in the emergency department immediately upon diagnosis. 1, 5

If patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 3

Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present. 1

Do not extend therapy beyond 7 days in responding patients without specific indications—this increases antimicrobial resistance risk without improving outcomes. 1

Diagnostic Testing for Hospitalized Patients

Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients. 1, 6

Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis may affect treatment and infection prevention strategies. 5