What is the recommended treatment for disseminated Cytomegalovirus (CMV) infection?

Treatment of Disseminated Cytomegalovirus (CMV) Infection

Intravenous ganciclovir 5 mg/kg twice daily for 2-3 weeks, with potential transition to oral valganciclovir 900 mg twice daily after clinical improvement, is the first-line treatment for disseminated CMV infection. 1

First-Line Treatment

• Initiate intravenous ganciclovir at 5 mg/kg twice daily for 2-3 weeks as the cornerstone of therapy for disseminated CMV infection 1
• After 3-5 days of IV therapy, if clinical improvement is observed and oral absorption is adequate, transition to oral valganciclovir 900 mg twice daily for the remainder of the 2-3 week course 1, 2
• For severe disseminated CMV infection, prompt initiation of antiviral therapy is critical for optimal clinical response 1
• Treatment should continue until CMV is no longer detected in blood and clinical symptoms have resolved 1

Alternative Treatment Options

• In cases of ganciclovir resistance or intolerance, foscarnet (60 mg/kg every 8 hours or 90 mg/kg every 12 hours) is the recommended alternative 1, 3
• For neurological CMV disease, combination therapy with ganciclovir and foscarnet might be preferred as initial therapy to maximize response, despite higher rates of adverse effects 1, 4
• Cidofovir can be considered as a third-line agent, though it carries substantial risk of nephrotoxicity 1, 4
• For CMV pneumonitis, adjunctive intravenous immunoglobulin (IVIG) can be administered, typically every other day for 3 to 5 doses 4

Special Patient Populations

• In immunocompromised patients (e.g., transplant recipients, HIV patients), discontinuation of immunosuppressive therapy should be considered when possible 1, 4
• For HIV-infected patients with CMV disease, antiretroviral therapy should be initiated or optimized concurrently with CMV treatment 1, 4
• In cases of severe disseminated CMV characterized by mononucleosis-like syndrome (fever, malaise, leukopenia, thrombocytopenia, elevated liver enzymes), discontinuation of immunosuppressive therapy is strongly recommended 4

Monitoring During Treatment

• Weekly monitoring of CMV viral load by PCR is essential to assess treatment response 1
• Complete blood counts and serum electrolytes should be monitored twice weekly during induction therapy and once weekly thereafter due to potential hematologic toxicity 4
• Renal function should be closely monitored, especially with foscarnet or cidofovir therapy 1, 3
• Ophthalmologic examination is recommended for patients with suspected CMV retinitis 4

Management of Adverse Effects

• Ganciclovir and valganciclovir commonly cause neutropenia, thrombocytopenia, anemia, nausea, diarrhea, and renal dysfunction 1, 2
• Foscarnet frequently causes nephrotoxicity, electrolyte abnormalities (particularly calcium, phosphorus, magnesium, and potassium), and neurologic dysfunction 1, 3
• For patients receiving foscarnet, adequate hydration with saline is recommended to reduce nephrotoxicity 4
• Dose adjustments based on renal function are critical for all anti-CMV agents to minimize toxicity 2, 3

Treatment Duration and Follow-up

• Treatment should continue for at least 2-3 weeks and until CMV is no longer detected in blood 1
• For patients with CMV retinitis, regular ophthalmologic follow-up is needed even after successful treatment 4
• In transplant recipients, continued monitoring for recurrence is recommended, as CMV can reactivate, particularly during periods of increased immunosuppression 5

Pitfalls and Caveats

• Delayed initiation of therapy can lead to increased morbidity and mortality, so prompt diagnosis and treatment are essential 1
• Oral valganciclovir should not be used as initial therapy in patients with severe disease, impaired gastrointestinal absorption, or high viral loads 5
• Drug resistance can develop, particularly in patients with prolonged exposure to antiviral agents 6
• Combination therapy with ganciclovir and foscarnet should be considered for severe or progressive disease despite standard therapy 1
• Monitoring for drug-specific toxicities is crucial, as management of these adverse effects often requires dose adjustments rather than discontinuation of therapy 4