Herpes simplex encephalitis, treatment

Indications PO - acute treatment of herpes zoster (shingles) Initial episodes and the management of genital herpes Treatment of chickenpox (varicella) IV - treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients Treatment of herpes simplex encephalitis Treatment of neonatal herpes infections Treatment of varicella-zoster (shingles) infections in immunocompromised patients... 

Vidarabine inhibits vitally induced DNA polymerase more strongly than it does the endogenous enzyme. Its use is now limited to topical treatment of severe herpes simplex infection. Before the introduction of the better tolerated acyclovir, vidarabine played a major part in the treatment of herpes simplex encephalitis. 

Intravenous acyclovir is used in the treatment of herpes simplex encephalitis, neonatal HSV infection, and mucocutaneous HSV infection in immunocompromised individuals. Acyclovir ointment is used in the treatment of initial genital herpes but is not effective for recurrent disease. Ophthalmic acyclovir formulations, although not available in the United States, are effective in the treatment of herpes keratoconjunctivitis. 

Intravenous acyclovir is the treatment of choice for herpes simplex encephalitis, neonatal HSV infection, and serious HSV or VZV infections (Table 49-1). In immunocompromised patients with VZV infection, intravenous acyclovir reduces the incidence of cutaneous and visceral dissemination. 

An immediately life-threatening disease means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months, or in which premature death is likely without early treatment. For example, advanced cases of AIDS, herpes simplex encephalitis, and subarachnoid hemorrhage are all considered immediately life-threatening diseases. Treatment INDs are made available to patients before general marketing begins, typically... 

Acyclovir is the drug of choice for herpes simplex encephalitis. In patients with normal renal function, acyclovir is usually administered as 10 mg/kg intravenously every 8 hours for 2 to 3 weeks. Herpes virus resistance to acyclovir has been reported with increasing incidence, particularly from immunocompromised patients with prior or chronic exposures to acyclovir. The alternative treatment for acyclovir-resistant herpes simplex virus is foscarnet. The major toxicity of foscarnet is renal impairment, and doses must be individualized for renal function. The dose for patients with normal renal function is 40 mg/kg infused over 1 hour every 8 to 12 hours for 2 to 3 weeks. Ensuring adequate hydration is imperative. In addition, patients receiving foscarnet should be monitored for seizures related to alterations in plasma electrolyte levels. 

Acyclovir is more effective the more serious the disease and the earlier it is given. It has been shown to be efficacious when used systemically in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephalitis in humans (68). 

Uric acid nephrolithiasis calcium renal stones Malignant mesothelioma Status epilepticus Herpes simplex encephalitis Neurosyphilis Status epilepticus Cognitive dysfunction Malignant non-Hodgkin s lymphomas Treatment of PCP associated with AIDS Acanthamoeba keratitis Peripheral arterial occlusive disease Congenital or acquired protein C deficiency Respiratory distress syndrome associated with prematurity... 

Vidarabine is used mainly in human HSV-1 and HSV-2 encephalitis, decreasing the mortality rate from 70 to 30%. Whitley et al. (57) reported that early vidarabine therapy is helpful in controlling complications of localized or disseminated herpes zoster in immunocompromised patients. Vidarabine also is useful in neonatal herpes labialis or genitalis, vaccinia virus, adenovirus, RNA viruses, papovavirus, CMV, and smallpox virus infections. Given the efficacy of vidarabine in certain viral infections, the U.S. FDA approved a 3% ointment for the treatment of herpes simplex keratoconjunctivitis and recurrent epithelial keratitis, and a 2% IV injection for the treatment of herpes simplex encephalitis and herpes zoster infections (Table 43.3). A topical ophthalmic preparation of vidarabine is useful in herpes simplex keratitis but shows little promise in herpes simplex labialis or genitalis. The monophosphate esters of vidarabine are more water-soluble and can be used in smaller volumes and even intramuscularly. These esters are under clinical investigation for the treatment of hepatitis B, systemic and cutaneous herpes simplex, and herpes zoster virus infections in immunocompromised patients. 

Nucleosides - Although 5-iododeoxyuridine (Ldoxuridine lUM "Stoxil" "Herplex ) has proven successful in the treatment of herpetic keratitis of the eyes, it has been less successful in the treatment of herpes simplex encephalitis. Using labelled lUDR it was found that insignificant amounts of lUMt entered the brain after IV injection (67). 

In addition, brain tissue was found to rapidly break down lUIXL to lU I + U and the authors concluded that this was the reason for lack of efficacy. Recent very limited studies in humans indicated that early treatment of herpes simplex encephalitis with IV lUI . and external decompression was not only life-saving, but prevented permanent brain damage... 

Herpes simplex virus encephalitis after myxedema coma has been described in an 81-year-old man treated with hydrocortisone (100 mg 8-hourly) and levothyroxine (328). In renal transplantation, two cases of death from Herpes simplex as a result of glucocorticoid treatment are on record (SED-8, 827 SEDA-17, 449). 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Herpes simplex virus type 1 (HSV-1) is a member of the Herpesviridae family. HSV infection is endemic in the population. The primary symptom of infection is recurrent fever blisters. On occasion, infection can lead to more serious symptoms such as encephalitis and retinitis. In particular, immunocompromised patients, such as those undergoing chemotherapy treatments or receiving organ transplants, and acquired immunodeficiency syndrome (AIDS) victims are at particular risk of developing life-threatening complications due to reactivation of latent infections. 

Parenteral acyclovir is the drug of choice for the treatment of initial and recurrent mucosal or cutaneous herpes simplex infections in immunocompromised patients and for the treatment of disseminated, neonatal, encephalitic, and severe first episodes of genital herpes simplex infections in immunocompetent patients (Whitley, 1997). Intravenous acyclovir should also be used for severe diseases such as encephalitis (Brady and Bernstein, 2004). 

Vidarabine, an antiviral agent (10 to 15 mg/kg/day for 5 to 10 days), is indicated in the treatment of herpes simplex virus encephalitis, neonatal herpes simplex virus infections, and herpes zoster in immunosuppressed patients. In addition, vidarabine (ophthalmic ointment 3% vidarabine monohydrate [equivalent to 2.8% vidarabine]) is indicated in the treatment of acute keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus types 1 and 2, or superficial keratitis caused by herpes simplex virus that has not responded to topical idoxuridine or when toxic or hypersensitivity reactions to idoxuridine have occurred. 

It is an antimetabolite of thymidine and, therefore, may be incorporated into deoxyribonueleic aeid in plaee of thymidine, thus interfering with usual nuelear metabolism. It is solely employed for the topieal therapy of herpes simplex keratitis of the eye. It has also been administered intravenously for the treatment of herpetic encephalitis. 

It is specifically employed for the treatment of herpes simplex virus infeetions belonging to Types 1 and 2 encephalitis. 

Rand, K.H. Bodor, N. el Koussi, AA. Raad, I. Miyake, A. Houck, H. Gildersleeve, N. Potential treatment of herpes simplex virus encephalitis by brain-specific delivery of trifluorothymidine using a dihydropyridine in equilibrium pyridinium salt type redox delivery system, J.Med.Virol., 1986, 20, 1-8. 

Viral infections that occur after transplantation are not limited to the lung. Herpes simplex infections are frequent early after the procedure, manifesting as oral vesicles or ulcerations. Less frequent is genital involvement by herpes simple virus, hepatitis or encephalitis. Herpes zoster and varicella reactivate in most patients, particularly if aciclovir prophylaxis is discontinued. Occasionally, severe cerebral arteritis or pneumonia caused by this virus may occur. CMV infection is frequent after transplantation and has to be regularly monitored by antigenemia and/or PCR for early treatment avoiding CMV disease. Epstein Barr virus (EBV) infection and EBV-associated lymphoproliferative disorders have also to be tested on a regular basis, especially in transplants with in... 

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