What are the recommended antibiotics for treating soft tissue cellulitis?

Recommended Antibiotics for Soft Tissue Cellulitis

For nonpurulent cellulitis, first-line treatment should be antibiotics active against streptococci, such as penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin for a 5-6 day course. 1

Antibiotic Selection Algorithm

1. Uncomplicated Cellulitis (No Systemic Signs)

• First-line therapy: Antibiotics active against streptococci 1
  • Penicillin
  • Amoxicillin
  • Dicloxacillin
  • Cephalexin (500 mg four times daily)
  • Clindamycin (if penicillin-allergic)

2. Cellulitis with Systemic Signs of Infection

• Recommended therapy: Coverage for both streptococci and MSSA 1
  • Cephalexin
  • Dicloxacillin
  • Clindamycin

3. Special Circumstances Requiring MRSA Coverage

MRSA coverage should be added when cellulitis is associated with:

• Penetrating trauma
• Evidence of MRSA infection elsewhere
• Nasal colonization with MRSA
• Injection drug use
• Systemic inflammatory response syndrome (SIRS)
• Athletes, prisoners, military recruits, residents of long-term care facilities 2

MRSA-active options:

• Oral: Trimethoprim-sulfamethoxazole, doxycycline, clindamycin
• IV: Vancomycin, daptomycin, linezolid, telavancin 1

4. Severely Compromised Patients

• Recommended therapy: Vancomycin plus either piperacillin-tazobactam or imipenem/meropenem 1

Duration of Therapy

• Standard duration: 5-6 days 1
• Extend treatment if infection has not improved after 5 days 1

Evidence Quality and Considerations

The 2021 American College of Physicians guideline 1 and 2014 IDSA guideline 1 both recommend a 5-day course of antibiotics for nonpurulent cellulitis, with extension if not improved. This shorter course is supported by multiple clinical trials showing similar efficacy to longer courses.

Recent research has clarified that MRSA is an unusual cause of typical cellulitis. The addition of MRSA coverage (trimethoprim-sulfamethoxazole) to cephalexin did not significantly improve outcomes in uncomplicated cellulitis in controlled trials 3, 4. However, in areas with high MRSA prevalence, trimethoprim-sulfamethoxazole showed higher success rates than cephalexin alone in a retrospective study 5.

Important Clinical Pearls

• Blood cultures are not routinely recommended but should be considered in patients with malignancy, neutropenia, severe immunodeficiency, immersion injuries, or animal bites 1
• Elevation of the affected area hastens improvement by promoting drainage of edema 1
• Examine interdigital toe spaces in lower-extremity cellulitis to identify and treat predisposing conditions 1
• Consider adjunctive anti-inflammatory therapy in non-diabetic patients (prednisone 40 mg daily for 7 days) to potentially hasten resolution 1, 6
• Treat predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities to reduce recurrence risk 1

Common Pitfalls to Avoid

1. Overuse of broad-spectrum antibiotics when narrow-spectrum agents targeting streptococci would suffice
2. Unnecessary MRSA coverage for typical cellulitis without risk factors
3. Failure to extend treatment when improvement is not seen after 5 days
4. Not addressing underlying conditions that predispose to cellulitis and recurrence
5. Prolonged antibiotic courses when shorter durations are equally effective

For patients with recurrent cellulitis (3-4 episodes per year), consider prophylactic antibiotics such as oral penicillin or erythromycin twice daily for extended periods, or intramuscular benzathine penicillin every 2-4 weeks 1.