What is the next step in managing a patient with herpes simplex virus infection, presenting with vesicular lesions, purulent drainage, and erythema, who is currently taking valacyclovir (Valtrex) three times a day and applying acyclovir (Zovirax) ointment?

Management of Extensive HSV Infection with Purulent Drainage on Current Antiviral Therapy

Immediate Action Required

This patient requires urgent evaluation for bacterial superinfection and consideration of IV foscarnet for potential acyclovir-resistant HSV, given the presence of purulent drainage, extensive lesions across multiple sites, and apparent treatment failure despite appropriate oral valacyclovir therapy. 1

Critical Assessment Steps

1. Rule Out Bacterial Superinfection

• Obtain bacterial cultures immediately from the purulent drainage, as the presence of purulent material with surrounding erythema and tenderness strongly suggests secondary bacterial infection (typically Staphylococcus aureus or Streptococcus pyogenes) 1
• Start empiric antibiotic coverage for skin and soft tissue infection while awaiting culture results
• The combination of HSV lesions with purulent drainage is NOT typical of uncomplicated HSV and demands bacterial workup

2. Evaluate for Antiviral Resistance

• If lesions persist after 7-10 days of appropriate valacyclovir therapy, HSV resistance must be considered 1
• Send viral cultures with HSV susceptibility testing if available 2
• All acyclovir-resistant strains are also resistant to valacyclovir, so increasing the valacyclovir dose further will not help 1

Treatment Algorithm

If Bacterial Superinfection Confirmed or Highly Suspected:

• Add appropriate systemic antibiotics (e.g., cephalexin 500mg four times daily or doxycycline 100mg twice daily for 7-10 days)
• Continue valacyclovir at current dose (three times daily dosing is appropriate for severe disease) 1
• Discontinue topical acyclovir ointment—topical antivirals are not effective for suppressive therapy or severe disease as they cannot reach the site of viral reactivation 3

If HSV Resistance Suspected (lesions not improving after 7-10 days of valacyclovir):

• Initiate IV foscarnet 40 mg/kg every 8 hours until clinical resolution 1, 2
• Foscarnet is the treatment of choice for acyclovir-resistant HSV 1
• Ensure adequate hydration and monitor renal function closely during foscarnet therapy 2
• Alternative: If lesions are accessible, consider topical trifluridine (TFT) ophthalmic solution applied 3-4 times daily 2

If Immunocompromised Status Present:

• Risk of acyclovir resistance increases to 7% in immunocompromised patients (versus <0.5% in immunocompetent hosts) 3
• Consider earlier transition to foscarnet if poor response within 5-7 days 2
• Higher and more prolonged antiviral dosing may be required 3

Correct Current Medication Errors

Valacyclovir Dosing:

• The current "three times daily" dosing is NOT standard for any HSV indication 4, 1, 5
• For severe recurrent genital herpes: valacyclovir 500mg twice daily for 5 days 4
• For cold sores: valacyclovir 2g twice daily for 1 day 3, 5
• For suppressive therapy with frequent recurrences: valacyclovir 500mg-1000mg once daily 1
• Clarify the intended indication and correct the dosing regimen accordingly

Topical Acyclovir:

• Discontinue topical acyclovir ointment—it provides only modest clinical benefit and is far less effective than oral therapy 3
• Topical antivirals cannot reach the site of viral reactivation in nerve ganglia 3
• The combination adds no meaningful benefit to oral therapy 3

Common Pitfalls to Avoid

• Failing to recognize bacterial superinfection in HSV lesions with purulent drainage—this is NOT typical HSV presentation 1
• Continuing to escalate oral acyclovir/valacyclovir doses when resistance is present—all acyclovir-resistant strains are cross-resistant to valacyclovir 1
• Relying on topical antivirals for severe or extensive disease—these are ineffective for anything beyond very mild localized lesions 3
• Delaying foscarnet therapy in immunocompromised patients with treatment failure—resistance develops more readily in this population 3, 2

Monitoring and Follow-Up

• Reassess clinically within 48-72 hours after initiating antibiotics (if bacterial infection suspected)
• If no improvement after 5-7 days of appropriate therapy, strongly consider HSV resistance and transition to foscarnet 2
• Monitor renal function if foscarnet is initiated 2
• Once acute episode resolves, consider daily suppressive therapy (valacyclovir 500mg-1000mg once daily) if patient has ≥6 recurrences per year 4, 1