What is the next step for a patient with breast side skin cellulitis/wound infection who did not respond to Keflex (Cephalexin)?

Management of Breast Side Skin Cellulitis/Wound Infection After Cephalexin Failure

For a patient with breast side skin cellulitis/wound infection who did not respond to Keflex (cephalexin), the next step should be switching to clindamycin, trimethoprim-sulfamethoxazole, or doxycycline to provide coverage for potential methicillin-resistant Staphylococcus aureus (MRSA). 1, 2

Evaluation of Treatment Failure

Before switching antibiotics, consider:

• Confirming the diagnosis is truly cellulitis (not inflammatory breast cancer, dermatitis, etc.)
• Obtaining cultures if possible, especially if:
  • There are systemic signs of infection
  • The patient has risk factors for MRSA
  • There is purulent drainage
  • The patient is immunocompromised 2
• Assessing for an undrained abscess using ultrasound if available

Antibiotic Selection After Cephalexin Failure

First-line options:

1. Clindamycin: 300-450 mg orally four times daily for 5-7 days 1

   • Provides coverage against both streptococci and MRSA
   • Caution: Risk of C. difficile colitis

2. Trimethoprim-sulfamethoxazole (TMP-SMX): 1-2 double-strength tablets twice daily for 5-7 days 1

   • Excellent MRSA coverage
   • Less optimal for streptococcal coverage
   • Avoid in pregnancy and sulfa allergy

3. Doxycycline: 100 mg twice daily for 5-7 days 1, 3

   • Effective against MRSA and streptococci
   • Recent evidence shows comparable efficacy to cephalexin for presumed streptococcal infections 3
   • Avoid in pregnancy and children under 8

For severe infections or systemic symptoms:

• Consider hospitalization for IV antibiotics if:

  • Fever >38°C (100.4°F)
  • Significant comorbidities
  • Rapid progression of infection
  • Failed outpatient therapy
  • Immunocompromised state 2

• IV options include:

  • Vancomycin (MRSA coverage)
  • Linezolid
  • Daptomycin
  • Ceftaroline 1

Evidence for Antibiotic Selection

The choice of second-line therapy should be guided by local resistance patterns and patient factors. Research shows that in areas with high MRSA prevalence, antibiotics with MRSA activity (TMP-SMX, clindamycin) have higher success rates than cephalexin for cellulitis 4.

A randomized trial comparing cephalexin alone versus cephalexin plus TMP-SMX showed no significant benefit of combination therapy in the per-protocol analysis, though there was a trend toward benefit in the intention-to-treat analysis 5, 6. This suggests that for patients who have already failed cephalexin, switching to an agent with MRSA activity rather than adding one is a reasonable approach.

Additional Management Considerations

• Elevate the affected area to reduce edema and promote healing 2
• Mark the borders of erythema to monitor progression
• Reassess within 48-72 hours to evaluate response to the new antibiotic 2
• Consider wound care if applicable
• Treat predisposing factors (e.g., lymphedema, skin conditions) 2

Duration of Therapy

The recommended duration is 5-7 days, but treatment should be extended if the infection has not improved within this time period 1, 2.

Prevention of Recurrence

For patients with recurrent skin infections:

• Consider decolonization with intranasal mupirocin and chlorhexidine washes 1
• Address underlying conditions that may predispose to infection
• Consider prophylactic antibiotics for patients with 3-4 episodes per year 2