What is the treatment approach for recalcitrant herpes simplex infections?

Treatment Approach for Recalcitrant Herpes Simplex Infections

For recalcitrant herpes simplex infections, treatment should be escalated to higher doses of oral antivirals, followed by intravenous antivirals, and then alternative agents such as foscarnet or cidofovir when resistance is suspected. 1

Initial Assessment and Standard Treatment

• Recalcitrant herpes simplex infections are most commonly seen in immunocompromised patients, who may not be able to control HSV infection effectively and often develop severe disease refractory to standard antiviral therapy 1
• Standard first-line treatment for herpes simplex infections includes:
  • Acyclovir 200 mg orally 5 times daily for 7-10 days for first clinical episodes 2
  • Acyclovir 400 mg orally 5 times daily for 10 days for herpes proctitis 2
  • For recurrent episodes: acyclovir 200 mg orally 5 times daily, 400 mg 3 times daily, or 800 mg twice daily for 5 days 2

Treatment Algorithm for Recalcitrant HSV Infections

Step 1: Increase Oral Antiviral Dose

• If standard doses fail to produce adequate response within 3-5 days, increase acyclovir to 800 mg orally five times daily 1
• Alternatively, consider switching to valacyclovir 1000 mg twice daily or famciclovir 500 mg twice daily for improved bioavailability 3, 2
• Obtain cultures to verify HSV etiology and consider requesting acyclovir susceptibility testing if available 1

Step 2: Consider Intravenous Therapy

• If no response is seen after 5-7 days of high-dose oral therapy, initiate intravenous acyclovir 1
• Recommended IV acyclovir dosage: 5-10 mg/kg every 8 hours 4
• For immunocompromised patients with severe infection, use 10 mg/kg every 8 hours 4
• Monitor renal function and adjust dosage accordingly for patients with renal impairment 4

Step 3: Management of Suspected Acyclovir-Resistant HSV

• If lesions fail to respond to intravenous acyclovir after 5-7 days, suspect acyclovir resistance 1, 5
• For accessible mucocutaneous lesions, consider topical trifluridine applied 3-4 times daily until complete healing 1
• For inaccessible lesions or poor response to topical therapy, initiate intravenous foscarnet at 40 mg/kg three times daily or 60 mg/kg twice daily for 10 days 1, 5
• If foscarnet fails, consider intravenous cidofovir or topical 1-3% cidofovir ointment (compounded) 1, 5

Special Considerations

HIV-Infected Patients

• HIV-infected patients with HSV infections often require longer courses of therapy than recommended for immunocompetent individuals 2
• Higher doses of oral antivirals may be effective in cases that appear to demonstrate resistance to standard therapy 2
• For HIV patients with recalcitrant HSV, some experts suggest using the erythromycin 7-day regimen 2
• Patients with HIV should be monitored closely as healing may be slower and treatment failures more common 2

Prevention of Recurrence

• For patients with frequent recurrences (≥6 per year), consider suppressive therapy 3:
  • Acyclovir 400 mg twice daily 3
  • Valacyclovir 1 g daily 3
  • Famciclovir 250 mg twice daily 3
• These regimens are effective in suppressing 70-80% of symptomatic recurrences 3
• For HIV-infected patients, suppressive therapy should be considered but may not be effective in decreasing transmission risk 2

Monitoring and Follow-up

• Patients should be evaluated after 1 week of treatment if symptoms persist 2
• For patients on topical corticosteroids (sometimes used for associated inflammation), monitor IOP and pupillary dilation to evaluate for glaucoma and cataract 2
• For patients with HSV keratitis, secondary stromal keratitis may benefit from topical steroid treatment but only in conjunction with oral antiviral therapy 2

Pitfalls and Caveats

• Topical acyclovir is substantially less effective than oral therapy and its use is discouraged 2
• Topical trifluridine inevitably causes epithelial toxicity if used for more than 2 weeks 2
• Topical corticosteroids potentiate HSV infection and should be avoided unless used in conjunction with antiviral therapy 2
• Acyclovir resistance is rare in immunocompetent patients but more common in immunocompromised hosts 1, 5
• Viral culture with susceptibility testing is the preferred method to confirm acyclovir resistance 5