What are the recommended antibiotics for community-acquired pneumonia?

Recommended Antibiotics for Community-Acquired Pneumonia

For outpatient treatment of healthy adults without comorbidities, amoxicillin 1 gram three times daily is the first-line antibiotic, with doxycycline 100 mg twice daily as the preferred alternative. 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the first-line choice, providing optimal coverage against Streptococcus pneumoniae (the most common pathogen, accounting for 48% of identified cases) with activity against 90-95% of pneumococcal strains. 1, 2
• Doxycycline 100 mg orally twice daily for 5-7 days serves as the preferred alternative, offering broad-spectrum coverage including atypical organisms at significantly lower cost than fluoroquinolones. 1, 2
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily, or clarithromycin 500 mg twice daily) should ONLY be used if local pneumococcal macrolide resistance is documented to be <25%, as breakthrough pneumococcal bacteremia is significantly more common with macrolide-resistant strains. 1, 2

Adults With Comorbidities

Comorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppression; or recent antibiotic use within 90 days. 3

• Combination therapy: β-lactam PLUS macrolide is strongly recommended. 3, 1, 2

  • Amoxicillin-clavulanate 875 mg/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days 1
  • Alternative β-lactams: cefpodoxime, cefuroxime 500 mg twice daily, or ceftriaxone 3, 1

• Respiratory fluoroquinolone monotherapy is equally effective: 3, 1, 2

  • Levofloxacin 750 mg once daily for 5 days 1, 2
  • Moxifloxacin 400 mg once daily for 5-7 days 1, 2

However, fluoroquinolones should be reserved for patients with comorbidities or when other options cannot be used due to risks of tendinopathy, peripheral neuropathy, and CNS effects. 1

Inpatient Non-ICU Treatment

For hospitalized patients not requiring ICU admission, use either β-lactam PLUS macrolide combination therapy OR respiratory fluoroquinolone monotherapy. 3, 1, 2

Preferred Regimens (Both Equally Effective)

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV/oral daily (strong recommendation, high-quality evidence) 1, 2
• Levofloxacin 750 mg IV/oral daily as monotherapy (strong recommendation, high-quality evidence) 1, 2
• Moxifloxacin 400 mg IV/oral daily as monotherapy (strong recommendation, high-quality evidence) 1, 2

Alternative β-lactams

• Cefotaxime 1-2 g IV every 8 hours 3, 2
• Ampicillin-sulbactam 3 g IV every 6 hours 3, 2
• Ceftaroline (for high-level penicillin resistance) 1

For Penicillin-Allergic Patients

• Respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin) 3, 2
• Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily (for patients with contraindications to fluoroquinolones) 2

Inpatient ICU Treatment (Severe CAP)

For ICU patients, mandatory combination therapy with β-lactam PLUS either azithromycin OR respiratory fluoroquinolone is required. 3, 1, 2

Standard Severe CAP Regimen

• Ceftriaxone 2 g IV daily OR cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours 3, 2
• PLUS azithromycin 500 mg IV daily (level II evidence) OR levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily (level I evidence) 3, 2

When Pseudomonas Aeruginosa is Suspected

Risk factors include structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 2

• Antipseudomonal β-lactam: piperacillin-tazobactam, cefepime, imipenem, or meropenem 3, 2
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 3, 2
• OR antipseudomonal β-lactam PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily) PLUS azithromycin 3, 2

When MRSA is Suspected

Risk factors include post-influenza pneumonia, cavitary infiltrates on imaging, prior MRSA infection/colonization, or recent hospitalization with IV antibiotics. 2

• 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 3, 2

Treatment Duration

• Standard duration: 5-7 days for uncomplicated CAP once clinical stability is achieved (afebrile for 48-72 hours with no more than one sign of clinical instability). 1, 2
• Extended duration: 14-21 days ONLY for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to ingest medications, and has normal GI function—typically by day 2-3 of hospitalization. 2

Recommended Oral Step-Down Regimens

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily (preferred) 2
• Levofloxacin 750 mg orally daily (alternative) 1, 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 2
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance ≥25%, in patients with any comorbidities, or in those with recent antibiotic use. 1, 2
• Administer the first antibiotic dose while still in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 2
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 2
• Avoid automatically escalating to broad-spectrum antibiotics (antipseudomonal or anti-MRSA coverage) without documented risk factors. 2
• For patients with recent antibiotic exposure within 90 days, select an antibiotic from a different class to reduce resistance risk. 1, 2