What to do if a rash continues to spread despite treatment with Valtrex (valacyclovir)?

Management of Rash Spreading Despite Valacyclovir Treatment

If a rash continues to spread despite treatment with valacyclovir, the most likely cause is acyclovir/valacyclovir resistance, and the patient should be promptly referred to an infectious disease specialist for alternative therapy with foscarnet.

Evaluation Algorithm for Persistent Rash on Valacyclovir

Step 1: Assess for Antiviral Resistance

When lesions persist or continue to spread despite appropriate valacyclovir therapy, resistance of the herpes virus strain to acyclovir/valacyclovir should be suspected 1. This is particularly important to consider in:

• Immunocompromised patients
• Patients with HIV infection
• Patients with prolonged or multiple courses of antiviral therapy

Step 2: Determine Immune Status

• Check for signs of immunosuppression:
  • HIV testing (herpes zoster can be a harbinger of chronic HIV infection) 2
  • History of organ transplantation
  • Current immunosuppressive medications
  • Unexplained weight loss or lymphadenopathy

Step 3: Consider Alternative Diagnoses

• Rule out other causes of spreading rash:
  • Drug reaction to valacyclovir itself (rare but reported) 3
  • Bacterial superinfection of herpes lesions
  • Different viral or bacterial etiology

Treatment Recommendations

For Suspected Acyclovir/Valacyclovir Resistance:

1. Consult with an infectious disease specialist immediately
2. Switch to foscarnet therapy:
   • Foscarnet 40 mg/kg IV every 8 hours until clinical resolution 1
   • This is the treatment of choice for acyclovir-resistant herpes infections

Important Considerations:

• All acyclovir-resistant strains are also resistant to valacyclovir 1
• Most acyclovir-resistant strains are also resistant to famciclovir 1
• Continuing valacyclovir in the setting of resistance will not improve the condition and may select for further resistance

Alternative Topical Therapy:

• Topical cidofovir gel 1% applied to lesions once daily for 5 consecutive days may be effective 1
• This can be used as an adjunct to systemic therapy or in cases where IV foscarnet is not immediately available

Special Populations

Immunocompromised Patients:

• Higher doses of antivirals are often required 1
• For HIV-infected patients with herpes zoster, consider:
  • Acyclovir 400 mg orally 3-5 times daily until clinical resolution 1
  • For severe cases: acyclovir 5 mg/kg IV every 8 hours 1

Pregnant Women:

• The safety of systemic acyclovir and valacyclovir in pregnancy has not been fully established
• For life-threatening maternal HSV infection, IV acyclovir is indicated 1

Pitfalls to Avoid

1. Continuing ineffective therapy: Continuing valacyclovir when resistance is suspected may delay appropriate treatment
2. Misdiagnosis: Not all spreading rashes are treatment failures - consider drug reactions to valacyclovir itself
3. Missing immunodeficiency: Failure to respond to therapy may indicate underlying immunodeficiency that requires investigation
4. Inadequate dosing: Ensure patient was taking the correct dose (typically 1g three times daily for herpes zoster) 4

Remember that prompt consultation with specialists and rapid institution of alternative therapy are essential to prevent complications from progressive infection.