Immunocompromised patients herpes zoster infections

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 zoster, intravenous acyclovir reduces the incidence of cutaneous and visceral dissemination. 

Oral famciclovir is used for the treatment of immrmo-competent patients with herpes zoster infections and for the treatment and suppression of recuri ent genital HSV. It is also indicated for the treatment of recuri ent mucocutaneous herpes simplex in both immrmocompetent and immunocompromised patients. Famciclovir is fairly well tolerated. Adverse effects include headache, dizziness, nausea, and diarihea (Scholar and Pratt, 2000). 

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. 

Neonatal herpes simplex virus infection Treatment of neonatal herpes infections. Parenteral Treatment of initial and recurrent mucosal and cutaneous herpes simplex virus (HSV)-I and -2 and varicella-zoster virus (VZV/shingles) infections in immunocompromised patients. 

Topical aciclovir has limited effectivity in the treatment of recurrent herpes genitalis or herpes febrilis infections in non-immunocompromised patients, although topical aciclovir may cause some reduction in the duration of viral shedding. Topical aciclovir has no role in the treatment of herpes zoster. 

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... 

Varicella-zoster virus is a member of the Herpesviridae femily. The viral contagion is transmitted via aerosolized water droplets or close physical contact with infected lesions. The primary infection results in varicella or chickenpox. The varicella infection can have potentially devastating ocular sequelae the most common is anterior uveitis followed by SPK. After the primary infection, latent infection occurs in multiple ganglia throughout the body. Herpes zoster is the resultant reactivation of the latent varicella-zoster virus and most often occurs in elderly and immunocompromised patients. Factors such as physical and emotional trauma, immunosuppressive medications, irradiation, cancer, tuberculosis, malaria, and syphilis are known to reactivate the virus. 

Therapy for herpes zoster should be aimed at accelerating healing, limiting the severity and duration of acute and chronic pain and reducing any complications associated with the infection. In patients who are immunocompromised, therapy should also be aimed at reducing the risk of viral dissemination. Acyclovir, valacyclovir, and famciclovir are all used in the United States for the treatment of herpes zoster. Acyclovir is approved in the U.S. for the treatment of both chickenpox and herpes zoster in the normal host. Oral acyclovir therapy in normal children, adolescents, and adults shortens the duration of lesion formation by about a day, reduces the total number of new lesions by abont 25%, and reduces many of the symptoms in abont a third of patients (Gnann and Whitley, 2002 Snoeck et al., 1999). 

Acyclovir is useful for treating infections caused by HSV, herpes zoster, and for VZV infections (Whitley and Roizman, 2001). Although HCMV is relatively resistant to acyclovir, some cytomegalovirus infections have responded marginally to large doses of acyclovir, and it seems to be effective for the prophylaxis of cytomegalovirus infections in immunocompromised patients. Epstein-Barr virus is not sensitive to acyclovir, and clinical infections do not respond to the drug. 

Parenteral acyclovir (e.g., 5 mg/kg infused at a constant rate over 1 hour every 8 hours for 7 days) may be used in mucosal and cutaneous herpes simplex virus infections, and in varicella zoster infections (shingles) in immunocompromised patients and in herpes simplex encephalitis. 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

THERAPEUTIC USES In immunocompetent persons, the clinical benefits of acyclovir and valacyclovir are greater in initial HS V infections than in recurrent ones, which typically are milder. These drugs are particularly useful in immunocompromised patients because these individuals experience more frequent and more severe HSV and VZV infections. Since VZV is less susceptible than HSV to acyclovir, higher doses must be used for treating varicella or zoster infections. Oral valacyclovir is as effective as oral acyclovir in HSV infections and more effective for treating herpes zoster. 

Vidarabine Vidarabine is an adenine analog and has activity against HSV, VZV, and CMV. Its use for systemic infections is limited by rapid metabolic inactivation and by marked toxic potential. However, it has been used intravenously for severe HSV infections, including those resistant to acyclovir, and it also prevents the dissemination of varicella-zoster virus in immunocompromised patients. Vidarabine is used topically for herpes keratitis, but it has no effect on genital lesions. Toxic effects with systemic use include gastrointestinal irritation, paresthesias, tremor, convulsions, and hepatic dysfunction. Vidarabine is teratogenic in animals. 

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