Cytomegalovirus infection in non-immunocompromised critically ill patients: A management perspective

Table 4 Therapeutic options for cytomegalovirus

No.	Drug	Mechanism	Dose	Salient features	Adverse effects
1	Ganciclovir1[63]	Nucleoside analog, needs intracellular phosphorylation to inhibit DNA polymerase, hence can develop resistance	5 mg/kg iv q12h	Preferable in life threatening disease, very high viral load and when there is a concern for inadequate gastrointestinal absorption	Severe neutropenia may become a therapy limiting adverse effect in up to 32% patients. May respond to G-CSF or GM-CSF
2	Valganciclovir1	Prodrug of ganciclovir	900 mg po q12h	Oral bioavailability is equivalent to iv ganciclovir, once-daily dosing and reduced risk of development of resistance	Neutropenia, thrombocytopenia, anemia, acute renal failure
3	Foscarnet or Phosphonoformate1	Does not require intracellular phosphorylation and therefore, retains activity against most GCV-resistant strains of CMV	90 mg/kg iv q12h	Intravenous PFA may be used under conditions of failure of GCV treatment, GCV resistance or excessive side effects such as leukopenia	PFA is nephrotoxic in 1/3rd patients, which limits its use in many critically ill patients
4	Cidofovir1	Acts directly on DNA polymerase	5 mg/kg iv once weekly	May be used as an alternative to PFA in case of GCV resistance. FDA approved only for CMV retinitis in HIV	Nephrotoxic on proximal tubular cells (Fanconi like syndrome). Pre-hydration and probenecid before the dose
5	Maribavir1[64] (Livtencity, Takeda)	Inhibition of human CMV encoded kinase pUL97: Required for viral replication	400 mg po q12h	Used in resistance to GCV, PFA, CDV	No renal or hepatic dose adjustment required. It can cause nausea, vomiting, diarrhea and neutropenia
6	Letermovir1[65] (Prevymis, Merck)	CMV viral terminase inhibitor	480 mg q24h po or iv	FDA approval for post HSCT and post renal transplant prophylaxis	Nausea, diarrhoea, vomiting, oedema. Various drug interactions requiring dose adjustments
7	Hyperimmune serum	Passive immune prophylaxis	400 U/kg on day 1, 4 and 8 and then 200 U/kg on day 12 and 16	As salvage therapy in severe recurrent CMV infections	High cost and heterogeneity of the preparation. Infusion related adverse effects like fever, shivering, rash

¹United States Food and Drug Administration approved for treatment of cytomegalovirus in immunocompromised patients.

CMV: Cytomegalovirus; G-CSF: Granulocyte colony stimulation factor; GM-CSF: Granulocyte macrophage colony stimulation factor; GCV: Ganciclovir; CDV: Cidofovir; PFA: Phosphonoformate; DNA: Deoxy ribonucleic acid; FDA: Food and drug administration; HSCT: Hematopoietic stem cell transplantation; DNA: Deoxyribose nucleic acid; HIV: Human immunodeficiency virus; iv: Intravenous; po: Per oral.