What is the recommended treatment for cytomegalovirus (CMV) infection in immunocompromised patients?

Treatment of Cytomegalovirus (CMV) Infection in Immunocompromised Patients

Intravenous ganciclovir 5 mg/kg twice daily for 3-5 days followed by oral valganciclovir 900 mg twice daily for a total duration of 2-3 weeks is the recommended first-line treatment for CMV disease in immunocompromised patients. 1, 2

Initial Treatment Regimen

For active CMV disease (colitis, pneumonitis, or other end-organ disease):

• Start with IV ganciclovir 5 mg/kg twice daily for the first 3-5 days 1, 2
• Transition to oral valganciclovir 900 mg twice daily after clinical improvement is observed, completing a total course of 2-3 weeks 1, 2
• All doses should be taken with food to optimize absorption 3
• Consult infectious disease specialists early in the treatment course 1

Critical management consideration: Withdrawal or reduction of immunosuppressive therapy should be strongly considered, as this is associated with clinical improvement and decreased mortality 1, 2

Alternative Treatment Options

When ganciclovir is not tolerated or resistance develops:

• Foscarnet administered for 2-3 weeks is the recommended alternative 1, 2
• Monitor closely for nephrotoxicity (occurs in ~25% of patients) and electrolyte abnormalities 1, 2
• Cidofovir can be considered as third-line therapy, though substantial nephrotoxicity risk limits its use 1, 2

For CMV neurological disease (encephalitis, myelitis):

• Combination therapy with ganciclovir plus foscarnet may be preferred initially to maximize response, despite higher adverse effect rates 2

For CMV pneumonitis:

• Consider adjunctive intravenous immunoglobulin (IVIG) every other day for 3-5 doses in addition to antiviral therapy 2

Monitoring During Treatment

Essential monitoring parameters include:

• Weekly CMV viral load by PCR to assess treatment response 1, 2
• Continue treatment until CMV is no longer detected in blood 2
• Complete blood counts to monitor for hematologic toxicity (neutropenia, thrombocytopenia, anemia) 2, 3
• Renal function particularly with foscarnet or cidofovir therapy 2
• Electrolytes especially with foscarnet (can cause significant abnormalities) 2

Context-Specific Considerations

In inflammatory bowel disease (IBD) patients with CMV colitis:

• Diagnosis requires colonic biopsy with histology and immunohistochemistry (IHC), which is the gold standard with 78-93% sensitivity 1
• CMV screening is mandatory in steroid-resistant acute severe ulcerative colitis 1
• The same treatment regimen applies: IV ganciclovir 5 mg/kg twice daily for 3-5 days, then valganciclovir 900 mg twice daily for 2-3 weeks 1

In hematopoietic stem cell transplant (HSCT) recipients:

• Pre-emptive therapy is preferred over universal prophylaxis due to ganciclovir toxicity and risk of delayed CMV-specific immune recovery 1
• Weekly monitoring by PCR or pp65 antigen detection should continue for at least 100 days post-transplant 1
• Extend monitoring to 1 year in patients with chronic GVHD, prolonged immunosuppression, or T-cell depletion 1
• Initiate treatment after a single positive pp65 antigen test or two consecutive positive CMV PCR assays 1

In solid organ transplant (SOT) recipients:

• Valganciclovir has proven efficacy for both pre-emptive therapy and treatment of CMV disease, with 83.9% success rates 4
• Treatment duration may be longer than in other populations (median 21 days for pre-emptive therapy) 4

In HIV/AIDS patients:

• For CMV retinitis: induction with 900 mg twice daily for 21 days, then maintenance with 900 mg once daily 3
• Optimize antiretroviral therapy (ART) concurrently with CMV treatment 2

Common Pitfalls and Adverse Effects

Hematologic toxicity is the most significant concern:

• Severe leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia can occur 3
• Bone marrow aplasia and aplastic anemia are rare but serious complications 3
• Monitor complete blood counts at least weekly during treatment 3

Other important adverse effects:

• Ganciclovir/valganciclovir: nausea, diarrhea, renal dysfunction, potential impairment of fertility 2, 3
• Foscarnet: nephrotoxicity (25%), electrolyte abnormalities (hypocalcemia, hypomagnesemia), neurologic dysfunction 1, 2
• Cidofovir: substantial nephrotoxicity and potential ocular toxicity 2

Resistance considerations:

• Ganciclovir resistance can develop with extended use, particularly in heavily immunosuppressed patients 1, 5
• If resistance is suspected (persistent viremia despite adequate therapy), switch to foscarnet 1
• Combination therapy may be needed for resistant cases 2

Prophylaxis vs. Treatment

Important distinction: The evidence provided focuses on treatment of active CMV disease, not prophylaxis. For prophylaxis in high-risk transplant recipients, letermovir has emerged as a preferred agent with lower toxicity than ganciclovir 1. However, once CMV disease develops, the treatment approach outlined above applies regardless of whether prophylaxis was used.