What are the recommended antibiotics for a typical adult patient with community-acquired pneumonia?

Antibiotic Selection for Community-Acquired Pneumonia in Adults

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

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

First-line therapy:

• Amoxicillin 1 gram orally three times daily for 5-7 days provides optimal coverage against Streptococcus pneumoniae (the most common pathogen, accounting for 48% of identified cases) and demonstrates activity against 90-95% of pneumococcal strains including many with intermediate penicillin resistance 1, 2

Alternative options:

• Doxycycline 100 mg orally twice daily for 5-7 days offers broad-spectrum coverage including atypical organisms and has demonstrated comparable efficacy to fluoroquinolones at significantly lower cost 1, 2, 3
• 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 to be <25% 1, 2

Adults With Comorbidities (COPD, diabetes, heart/lung/liver/renal disease, malignancy, immunosuppression)

Preferred regimen:

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5, total duration 5-7 days 1, 2
• This combination achieves 91.5% favorable clinical outcomes and provides dual coverage against typical bacterial pathogens and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1

Alternative monotherapy:

• Levofloxacin 750 mg orally once daily for 5 days provides equivalent efficacy with >98% activity against S. pneumoniae including penicillin-resistant strains 1, 2, 4
• Moxifloxacin 400 mg orally once daily for 5 days is equally effective 1, 2

Inpatient Treatment (Non-ICU)

Two equally effective regimens with strong evidence:

1. β-lactam plus macrolide combination:

   • Ceftriaxone 1-2 grams IV once daily PLUS azithromycin 500 mg daily (IV or oral) 1, 2
   • Alternative β-lactams: cefotaxime 1-2 grams IV every 8 hours or ampicillin-sulbactam 3 grams IV every 6 hours 1

2. Respiratory fluoroquinolone monotherapy:

   • Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2
   • Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 1

Transition to oral therapy when the patient is hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization 1, 2

Severe CAP Requiring ICU Admission

Mandatory combination therapy for all ICU patients:

• Ceftriaxone 2 grams IV once daily (or 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) 1, 2, 5
• Monotherapy is inadequate for severe disease and increases mortality risk 1

Special Populations Requiring Broader Coverage

Pseudomonas Risk Factors

Add antipseudomonal coverage if:

• Structural lung disease (bronchiectasis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa
• Recent broad-spectrum antibiotic use 1

Regimen: Antipseudomonal β-lactam (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) 1

MRSA Risk Factors

Add MRSA coverage if:

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging 1

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 the base regimen 1

Treatment Duration

Standard duration: Minimum of 5 days and until afebrile for 48-72 hours with no more than one sign of clinical instability; typical duration for uncomplicated CAP is 5-7 days 1, 2, 6

Extended duration (14-21 days) required for:

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

Critical Pitfalls to Avoid

1. Never use macrolide monotherapy in patients with comorbidities or in areas where pneumococcal macrolide resistance exceeds 25%—breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains 1, 2

2. Never delay antibiotic administration in hospitalized patients—the first dose must be given in the emergency department, as delays beyond 8 hours increase 30-day mortality by 20-30% 1

3. Never use β-lactam monotherapy for hospitalized patients—it provides inadequate coverage for atypical pathogens and increases mortality compared to combination therapy 1

4. Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendinopathy, peripheral neuropathy, CNS effects) and resistance concerns 1, 2

5. Select a different antibiotic class if the patient used antibiotics within the past 90 days to reduce resistance risk 1, 2

6. Never use ceftriaxone alone—it lacks activity against atypical pathogens and must be combined with a macrolide or fluoroquinolone 1

Penicillin-Allergic Patients

• Outpatient: Doxycycline 100 mg twice daily or respiratory fluoroquinolone 1, 2
• Inpatient non-ICU: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• ICU: Aztreonam 2 grams IV every 8 hours PLUS respiratory fluoroquinolone 1