What antibiotics are recommended for community-acquired pneumonia (CAP) aside from co-amoxiclav (amoxicillin-clavulanate)?

Alternative Antibiotics for Community-Acquired Pneumonia (Excluding Co-Amoxiclav)

Outpatient Treatment

For previously healthy adults without comorbidities, amoxicillin 1g three times daily is the preferred first-line alternative to co-amoxiclav, with macrolides (azithromycin or clarithromycin) or doxycycline 100mg twice daily as additional options. 1

Previously Healthy Patients (No Comorbidities)

• Amoxicillin 1g three times daily for 7 days is recommended as first-line therapy 1, 2
• Macrolides (azithromycin 500mg day 1, then 250mg daily; or clarithromycin 500mg twice daily) are acceptable alternatives, but should only be used in areas where pneumococcal macrolide resistance is <25% 2, 1
• Doxycycline 100mg twice daily is an acceptable alternative 2, 1
• Tetracyclines are listed as alternatives in European guidelines 2

Patients with Comorbidities (COPD, diabetes, renal/heart failure, malignancy)

• Respiratory fluoroquinolones (levofloxacin 750mg daily, moxifloxacin 400mg daily, or gemifloxacin) as monotherapy 2, 1
• Combination therapy: Advanced macrolide (azithromycin or clarithromycin) plus high-dose amoxicillin (1g three times daily) 2
• Alternative combination: Advanced macrolide plus cefuroxime, cefpodoxime, or cefprozil 2

Recent Antibiotic Use (within 3 months)

• Respiratory fluoroquinolone alone (if no recent fluoroquinolone use) 2
• Advanced macrolide plus high-dose amoxicillin (if recent fluoroquinolone use) 2
• Avoid using the same antibiotic class recently administered 2

Inpatient Treatment (Medical Ward)

For hospitalized patients with non-severe CAP, the preferred regimens are either a respiratory fluoroquinolone alone OR a beta-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus a macrolide. 2, 1

Standard Regimens

• Respiratory fluoroquinolone monotherapy: Levofloxacin 500-750mg daily or moxifloxacin 400mg daily 2, 1
• Beta-lactam plus macrolide combination:
  • Ceftriaxone 1-2g daily IV plus azithromycin 500mg daily 2, 1, 3
  • Cefotaxime 1g three times daily IV plus macrolide 2, 1
  • Ampicillin-sulbactam plus macrolide 2, 1
• Beta-lactam plus doxycycline is an alternative combination (lower quality evidence) 1

Penicillin-Allergic Patients

• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) is the preferred option 2, 1

European Guidelines Alternatives

• Penicillin G 1-4 million units every 2-4 hours IV plus macrolide 2
• Second-generation cephalosporin (cefuroxime 750-1500mg every 8 hours IV) plus macrolide 2

Intensive Care Unit (Severe CAP)

For ICU patients without Pseudomonas risk, use a beta-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus either azithromycin OR a respiratory fluoroquinolone. 2, 1

Standard Severe CAP (No Pseudomonas Risk)

• Third-generation cephalosporin plus macrolide: Ceftriaxone 2g daily or cefotaxime 1g three times daily plus azithromycin or erythromycin 500mg four times daily 2, 1
• Third-generation cephalosporin plus respiratory fluoroquinolone: Ceftriaxone or cefotaxime plus levofloxacin 750mg daily or moxifloxacin 400mg daily 2, 1
• Ampicillin-sulbactam can substitute for cephalosporins 2, 1

Beta-Lactam Allergy (No Pseudomonas Risk)

• Respiratory fluoroquinolone with or without clindamycin 2
• Aztreonam plus respiratory fluoroquinolone 2, 1

Pseudomonas Risk Factors Present

Risk factors include severe structural lung disease (bronchiectasis), recent antibiotic therapy, or recent ICU stay 2

• Antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin 400mg IV or levofloxacin 750mg daily 2
• Alternative: Antipseudomonal beta-lactam plus aminoglycoside plus respiratory fluoroquinolone or macrolide 2

Beta-Lactam Allergy with Pseudomonas Risk

• Aztreonam plus levofloxacin 750mg daily 2
• Aztreonam plus moxifloxacin or gatifloxacin, with or without aminoglycoside 2

Special Clinical Situations

Suspected Aspiration Pneumonia

• Clindamycin is the preferred alternative to amoxicillin-clavulanate 2

Influenza with Bacterial Superinfection

• Beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) or respiratory fluoroquinolone 2
• Consider adding oseltamivir if influenza is suspected or confirmed 4

Suspected MRSA

• Add vancomycin or linezolid to the standard regimen 2, 1

Treatment Duration

• Standard duration: 5-7 days for uncomplicated CAP 1
• Severe infections: 10-14 days may be required 2, 5
• Treatment should not exceed 8 days in patients responding adequately 4

Critical Clinical Considerations

High Macrolide Resistance Areas

• Avoid macrolide monotherapy when local S. pneumoniae macrolide resistance exceeds 25% 2, 1
• Respiratory fluoroquinolones are preferred in these settings 4, 1

Comparative Efficacy Evidence

• Ceftriaxone plus azithromycin demonstrated equivalent or superior outcomes compared to levofloxacin monotherapy in hospitalized patients, with 100% eradication of S. pneumoniae versus 44% with levofloxacin 6
• Levofloxacin 750mg for 5 days showed non-inferior efficacy to levofloxacin 500mg for 10 days 7

Common Pitfalls to Avoid

• Do not delay first antibiotic dose in hospitalized patients; administer while still in the emergency department 1
• Avoid fluoroquinolone use if patient received fluoroquinolones within the past 3 months 2
• Do not use aminoglycosides in elderly patients when alternatives exist, as they are associated with worse outcomes 2
• Consider local resistance patterns when selecting empiric therapy 2

Transition to Oral Therapy

• Switch from IV to oral when patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function 1