Continuous infusion of acyclovir is more effective than discontinuous infusion for treatment of genital herpes in an immunocompromised patient

Abstract

Recurrent genital herpes in immunocompromised patients may sometimes run a severe course spreading all over the perineum. Herpes simplex virus may develop resistance to acyclovir. A recurrent genital herpes simplex virus (HSV) infection complicating the treatment of Hodgkin's disease continued to spread in spite of acyclovir treatment via discontinuous infusion. Resolution of genital herpes was obtained with continuous infusion of acyclovir. Case ReportA 32-year-old woman had a history of recurrent genital herpes and received long-term treatment with oral acyclovir. Because of Hodgki.n's disease, chemotherapy and radiotherapy had been performed. A very low white blood cell and lymphocyte count was observed and the patient was consequently put on G-CSF (granuloeyte colony-stimulating factor). A disseminated eryptococcosis (fungemia, meningo-encephalitis, pneumonia) occurred and was treated with amphotericin B + 5 fluorocytosine, both intravenously, followed by fluconazole. Recurrent genital herpes appeared during the hospital stay, extending to a large placard over the perineum. The patient was then put on acyclovir IV 500 mg 1 h q.8 (i.e., 45 mg/kg/day). There was no improvement after 12 days of treatment. Therefore a continuous infusion of acyclovir was performed (2 g/day, 50 mg/kg/day) leading to recovery. The dosage of acyclovir was diluted to a total of 240 ml to be administered intravenously by a constant rate infusion.pump. The patient responded clinically within 6 days and by 14 days her lesions had healed, Unfortunately, we could neither carry out swabs from suspected lesions to isolate HSV, nor could we measure acyclovir levels in plasma.

Therapeutic Drug Monitoring of Continuous-Infusion Acylovir for Disseminated Herpes Simplex Virus Infection in a Neonate Receiving Concurrent Extracorporeal Life Support and Continuous Renal Replacement Therapy

“…From a safety perspective, acyclovir plasma concentrations would need to remain below 50–70 mg/L, as these concentrations have been associated with neurotoxicity in a small subset of patients . Continuous‐infusion acyclovir has been effective in treating HSV after conventional intermittent acyclovir treatment failure . However, to our knowledge, the use and pharmacokinetics of continuous‐infusion acyclovir in the setting of concurrent extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT) have never been described.…”

“…[7][8][9][10] Continuous-infusion acyclovir has been effective in treating HSV after conventional intermittent acyclovir treatment failure. [11][12][13][14][15] However, to our knowledge, the use and pharmacokinetics of continuous-infusion acyclovir in the setting of concurrent extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT) have never been described. In this case report, we describe the pharmacokinetics of continuous-infusion acyclovir in a patient receiving concurrent ECLS and CRRT.…”

Efficacy of Continuous Acyclovir Infusion in Neonatal Herpes Virus Encephalitis

“…We successfully eliminated herpes simplex virus-2 from the central nervous system in a patient with neonatal herpes simplex virus encephalitis using a continuous acyclovir infusion after conventional intermittent high-dose acyclovir and vidarabine failed. Some studies have reported on the effi cacy of continuous acyclovir infusion in herpes simplex virus, with or without acyclovir resistance, in immunodefi cient patients in whom intermittent acyclovir was not eff ective [1,4,7] . The diff erent effi cacies of these two therapies may be related to diff erent drug pharmacokinetics.…”

“…Pharmacokinetic studies in 16 immunosuppressed patients with Varicella-zoster virus or herpes simplex virus showed increased acyclovir penetration into the lesions with continuous infusion, resulting in vesicle fl uid levels near the plasma acyclovir levels [8] . As no reports exist on the serum and central concentrations of acyclovir suffi cient to eliminate herpes simplex virus in a case of herpes simplex virus encephalitis, we selected a dose of 2 mg / kg per hour, which is near the maximum reported safe and eff ective dose [1,4,7,8] . The therapy was eff ective clinically.…”

“…Incomplete herpes simplex virus removal sometimes occurs [5] , and is related to the poor prognosis of this disease. In cases with herpes simplex virus infection other than encephalitis, continuous acyclovir infusion has been eff ective in eliminating the virus after conventional intermittent acyclovir infusion failed [1,2,4,7] . Here, we report an infant with neonatal encephalitis due to herpes simplex virus-2, which intermittent high-dose acyclovir and vidarabine failed to eliminate, while continuous infusion of high-dose acyclovir succeeded.…”