What are the first-line antibiotic choices for treating cellulitis?

First-Line Antibiotic Choices for Cellulitis

For non-purulent cellulitis, cephalexin (500 mg orally 3-4 times daily for 5-6 days) is the recommended first-line antibiotic treatment. 1

Pathogen Coverage and First-Line Options

The majority of non-purulent, uncomplicated cellulitis cases are caused by β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus (MSSA). First-line treatment options include:

• Cephalexin: 500 mg orally 3-4 times daily for 5-6 days 1, 2
• Dicloxacillin: For MSSA infections 1
• Clindamycin: 300-450 mg orally three times daily for 5-6 days (alternative for penicillin-allergic patients) 1
• Amoxicillin-clavulanate: 875/125 mg twice daily orally for 5-6 days (for broader coverage) 1

Treatment Algorithm Based on Clinical Presentation

1. Uncomplicated, Non-purulent Cellulitis

• First choice: Cephalexin 500 mg 3-4 times daily for 5-6 days 1, 2
• If penicillin allergic: Clindamycin 300-450 mg three times daily for 5-6 days 1

2. Purulent Cellulitis or MRSA Risk Factors

Risk factors for MRSA include: athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, prior MRSA exposure, and intravenous drug users 3.

For these patients, consider:

• Trimethoprim-sulfamethoxazole: Shown to have higher success rates than cephalexin in areas with high MRSA prevalence 4
• Clindamycin: Particularly effective in culture-confirmed MRSA infections, moderately severe cellulitis, and obese patients 4

3. Severe Infections Requiring IV Therapy

• Vancomycin: 15 mg/kg IV every 12 hours 1
• Plus one of:
  • Piperacillin-tazobactam (4.5g IV q6h)
  • Cefepime (2g IV q8h)
  • Meropenem (1g IV q8h) 1

Important Clinical Considerations

Duration of Therapy

• 5-6 days is sufficient for uncomplicated cellulitis 1, 3
• Extend treatment if symptoms have not improved after this period 1

When to Suspect Treatment Failure

If no improvement is seen after 72 hours on oral therapy:

1. Reassess the diagnosis
2. Consider changing the antibiotic regimen 1
3. Consider MRSA coverage if not initially provided 3

Evidence on Combination Therapy

Recent high-quality evidence shows that adding trimethoprim-sulfamethoxazole to cephalexin did not significantly improve outcomes in uncomplicated cellulitis compared to cephalexin alone in the per-protocol analysis 5, 6. This supports the recommendation that MRSA coverage is generally not needed for non-purulent cellulitis 2.

Special Populations

Pediatric Patients

• Children under 8 years should not receive doxycycline due to risk of dental staining 1
• Use weight-based dosing for children

Pregnant Patients

• Avoid doxycycline 1
• Cephalexin is generally considered safe

Patients with Renal Impairment

• Dose adjustment required for cephalexin in patients with creatinine clearance <30 mL/min 1

Prevention of Recurrence

• Address predisposing factors:
  • Treat underlying skin conditions
  • Manage edema and venous insufficiency
  • Improve hygiene practices
  • Consider decolonization for recurrent MRSA infections 1

Remember that cellulitis is primarily a clinical diagnosis, and cultures are often negative. Treatment should be initiated based on clinical presentation, with consideration of local resistance patterns and patient-specific risk factors.