What is the treatment for a systemic viral infection?

Treatment of Systemic Viral Infection

For systemic viral infections, treatment is pathogen-specific and requires immediate identification of the causative virus, with antiviral therapy indicated only when there is clinical or laboratory evidence of specific viral disease—empirical antiviral therapy without documented viral infection is not recommended. 1

Cytomegalovirus (CMV) Systemic Disease

Initial Treatment Strategy

Intravenous ganciclovir 5 mg/kg twice daily is the first-line therapy for disseminated CMV infection, with transition to oral valganciclovir 900 mg twice daily after 3-5 days if clinical improvement occurs and oral absorption is adequate. 2, 3

• Continue treatment for 21-28 days total or until complete resolution of signs and symptoms 1, 2
• For CMV neurologic disease specifically, combination therapy with ganciclovir plus foscarnet may be preferred initially to maximize response, despite higher adverse effect rates 1, 3
• Prompt initiation of antiviral therapy is critical for optimal clinical outcomes in neurologic CMV disease 1, 3

Alternative Agents for CMV

• Foscarnet for 2-3 weeks is the recommended alternative in cases of ganciclovir resistance or intolerance (particularly myelotoxicity) 1, 3
• Cidofovir can be considered as third-line therapy but carries substantial nephrotoxicity risk 3
• For CMV pneumonitis, adjunctive intravenous immunoglobulin (IVIG) every other day for 3-5 doses may be beneficial 3

Organ-Specific CMV Treatment

• CMV colitis or esophagitis: IV ganciclovir or foscarnet (or oral valganciclovir if symptoms don't interfere with absorption) for 21-28 days 1
• CMV retinitis: Oral valganciclovir is preferable for peripheral non-sight-threatening lesions; ganciclovir intraocular implant plus valganciclovir for immediately sight-threatening lesions adjacent to optic nerve or fovea 1

Monitoring Requirements for CMV

• Twice-weekly monitoring during first 3-5 days: Complete blood count, serum creatinine, electrolytes, clinical symptom assessment 2
• Weekly monitoring during maintenance phase: Complete blood count, renal function, CMV viral load by PCR, clinical response 2, 3

Herpes Simplex Virus (HSV) Systemic Disease

Treatment Approach

• For severe systemic HSV disease, initiate intravenous acyclovir immediately and discontinue immunosuppressive agents until symptoms improve 1
• Oral therapy with acyclovir 400 mg twice daily, valacyclovir 500 mg daily, or famciclovir 250 mg twice daily is appropriate for suppressive prophylaxis in recurrent disease 1
• HSV encephalitis and life-threatening manifestations warrant IV acyclovir or foscarnet with careful multidisciplinary management 1

Varicella Zoster Virus (VZV) Systemic Disease

• Acyclovir, valacyclovir, and famciclovir are effective for systemic VZV infections 4
• These agents are phosphorylated by viral thymidine kinase and incorporated into DNA chains by viral DNA polymerase, resulting in chain termination 4

Influenza Virus Systemic Disease

Neuraminidase Inhibitors (First-Line)

Oseltamivir 75 mg orally twice daily for 5 days is the treatment of choice for influenza, initiated within 48 hours of symptom onset for maximum efficacy. 5, 6

• Treatment reduces median time to symptom improvement by 1.3 days compared to placebo 5
• M2 inhibitors (amantadine, rimantadine) are no longer effective due to universal resistance in circulating strains 1, 6
• Zanamivir, rimantadine, or amantadine are alternatives if oseltamivir is unavailable, though resistance patterns must be considered 1

Special Populations

• For immunocompromised patients with influenza, standard oseltamivir dosing (75 mg twice daily for 5 days) is appropriate 5
• In patients with chronic cardiac or respiratory disease, oseltamivir provides more rapid cessation of febrile illness 5

Respiratory Syncytial Virus (RSV)

• Ribavirin, especially when combined with intravenous antibody, reduces morbidity and mortality among immunosuppressed patients with RSV 6
• Ribavirin is indicated for documented RSV infection in febrile neutropenic patients 1

Critical Management Principles

When NOT to Treat

• Do not use empirical antiviral therapy in febrile neutropenic patients without evidence of viral disease 1
• Treatment of CMV viremia in the absence of organ system involvement is not recommended 1
• Asymptomatic viral shedding in immunocompromised patients does not require treatment 1

Immunosuppression Management

• For HIV-infected patients with systemic CMV disease, initiate or optimize antiretroviral therapy concurrently with CMV treatment 1, 3
• Continue CMV therapy until immune recovery (CD4+ count >100 cells/µL sustained for 3-6 months) 1
• For transplant or other immunosuppressed patients, reduce immunosuppression if clinically feasible 3
• Discontinuation of immunosuppressive agents is associated with clinical improvement and decreased mortality in severe CMV disease 3

Common Adverse Effects to Anticipate

Ganciclovir/valganciclovir: Neutropenia and thrombocytopenia (most common, dose-limiting), nausea, diarrhea, renal dysfunction 2, 3

Foscarnet: Nephrotoxicity, electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia), neurologic dysfunction including seizures 2, 3

Acyclovir: Generally well-tolerated; renal dysfunction with rapid IV administration 7

Oseltamivir: Nausea, vomiting, neuropsychiatric events (rare but monitor for abnormal behavior) 5

Diagnostic Confirmation Requirements

• Tissue biopsy with histopathology showing characteristic viral inclusions is the gold standard for mucosal CMV disease 2
• CMV PCR from blood or tissue supports diagnosis, but positive viral culture alone is insufficient in immunocompromised patients who may have asymptomatic shedding 2
• For HSV, immunohistochemistry or tissue PCR should be used to exclude HSV colitis before escalating immunosuppression 1