What is the best course of action for a patient with Methicillin-resistant Staphylococcus aureus (MRSA) cellulitis who develops a urticarial rash while on vancomycin (Vancomycin) therapy?

Management of Urticarial Rash in a Patient on Vancomycin for MRSA Cellulitis

Vancomycin should be discontinued immediately and replaced with an alternative antibiotic such as linezolid for the patient with MRSA cellulitis who has developed a urticarial rash after 10 days of therapy. 1, 2

Assessment of the Hypersensitivity Reaction

The urticarial rash represents a significant hypersensitivity reaction to vancomycin, which can range from mild reactions to severe manifestations including:

• Red man syndrome (related to rapid infusion)
• Urticarial rash (as in this case)
• Potential progression to more severe reactions such as DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) or toxic epidermal necrolysis 3

Immediate Management

1. Discontinue vancomycin immediately

   • Continued exposure can lead to worsening hypersensitivity reactions
   • Risk of progression to more severe cutaneous reactions or acute interstitial nephritis 3, 4

2. Administer antihistamines

   • H1 blockers (diphenhydramine 25-50 mg) for symptomatic relief
   • Consider adding H2 blockers (famotidine 20 mg) for enhanced effect

3. Consider short course of corticosteroids

   • Prednisone 40-60 mg daily for 3-5 days if reaction is moderate to severe
   • Taper if longer course is needed

Alternative Antibiotic Options

First-line alternative:

• Linezolid 600 mg PO twice daily 2, 5
  • Excellent efficacy against MRSA
  • Oral bioavailability equivalent to IV formulation
  • Demonstrated 79% cure rate for MRSA skin infections compared to 73% for vancomycin 5
  • Duration: Complete a total of 10-14 days of therapy (including previous vancomycin days)

Alternative options:

• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets (160/800 mg) twice daily 2
• Daptomycin 4-6 mg/kg IV once daily (if parenteral therapy required) 6
• Clindamycin 300-450 mg orally 3-4 times daily (if local resistance <10%) 2

Monitoring and Follow-up

1. Monitor for resolution of rash

   • Expect improvement within 24-72 hours after discontinuation of vancomycin
   • Document extent and progression/resolution of rash

2. Evaluate for systemic involvement

   • Check renal function (BUN, creatinine) as vancomycin can cause acute interstitial nephritis 3, 4
   • CBC with differential to assess for eosinophilia (marker of drug reaction)
   • Liver function tests to rule out hepatic involvement

3. Document vancomycin allergy

   • Clearly document in the patient's medical record
   • Educate patient about this allergy

Special Considerations

• Avoid vancomycin desensitization in this case, as safer alternatives exist for MRSA cellulitis 7
• Wound management should continue with appropriate debridement if needed 2
• Assess clinical response to the new antibiotic within 48-72 hours

Pitfalls to Avoid

1. Do not continue vancomycin with antihistamine premedication - this approach is insufficient for established hypersensitivity reactions and risks more severe reactions

2. Do not automatically switch to teicoplanin (where available) as cross-reactivity between glycopeptides can occur

3. Avoid unnecessary broad-spectrum coverage - focus on MRSA-targeted therapy as the pathogen is already identified

4. Do not delay antibiotic switch - prompt discontinuation of the offending agent is essential to prevent progression of hypersensitivity

Linezolid is particularly well-suited for this situation as it has demonstrated excellent efficacy against MRSA skin infections, has 100% oral bioavailability, and has a different mechanism of action from vancomycin, eliminating the risk of cross-reactivity 5, 8, 9.