Pediatric Cytomegalovirus Infection Medication

Experience with antiviral agents for cytomegalovirus (CMV) prophylaxis and cytomegalovirus therapy is limited in children. Administer anti–cytomegalovirus therapy only after consultation with an expert familiar with dosage and adverse effects. Antiviral agents may be administered therapeutically for established cytomegalovirus disease or prophylactically (ie, preemptive therapy) when the risk of development of cytomegalovirus disease is high (eg, in transplant recipients).

Class Summary

Nucleosides are the only true antiviral agents active against cytomegalovirus, although immunoglobulins may provide some antiviral effect, particularly in combination with these agents. These agents share a common molecular target, namely, the viral DNA polymerase. Biochemically, ganciclovir is an acyclic nucleoside analog, whereas cidofovir is an acyclic nucleoside phosphonate. Each compound must be phosphorylated to a triphosphate form before it can inhibit the cytomegalovirus polymerase. A viral gene product, the UL97 phosphotransferase, mediates the monophosphorylation step for ganciclovir. In contrast to these 2 agents, foscarnet is not a true nucleoside analog but can also directly inhibit the viral polymerase.

Ganciclovir is commonly used as preemptive therapy in transplant recipients at high risk of developing disease (eg, a cytomegalovirus–seronegative recipient of an organ transplant from a cytomegalovirus–seropositive donor). Oral and intravenous acyclovir has also been used successfully as prophylaxis for solid organ transplantation (seronegative recipient); however, never use acyclovir for cytomegalovirus therapy in active disease. An oral formulation is approved for use in adult patients infected with HIV who have cytomegalovirus retinitis; however, the bioavailability is poor, and no data support use in children.

Relatively little information concerning the use of ganciclovir in the setting of congenital cytomegalovirus infection is available. Because some of the neurological sequelae of congenital cytomegalovirus, particularly sensorineural hearing loss, progress postnatally, the presentation of results from a terminated nationwide collaborative trial are of interest. Intravenous ganciclovir led to improvement or stabilization of hearing in a significant number of 6-month-old infants. Case reports have suggested the efficacy of ganciclovir for acutely ill neonates with life-threatening cytomegalovirus disease (eg, pneumonia).

Alternatives to ganciclovir include trisodium phosphonoformate (PFA) and cidofovir. Pediatric experience with these agents is limited. Although potentially useful in the setting of ganciclovir resistance, the toxicities of these antivirals are significant. Use these agents only in pediatric patients in exceptional circumstances. Although they have only a modest level of activity against cytomegalovirus, high-dose oral acyclovir and valacyclovir have been used for prophylaxis of cytomegalovirus in high-risk individuals but are not suitable for therapy of active disease. Oral therapy with valganciclovir is considered to be investigational in children.

Ganciclovir (Cytovene)

First compound licensed for treatment of CMV infections. A synthetic acyclic nucleotide structurally similar to guanine. Its structure is similar to that of acyclovir; like acyclovir, it requires phosphorylation for antiviral activity. The enzyme responsible for phosphorylation is the product of the viral UL97 gene, a protein kinase. Resistance may occur with long-term use, generally because of mutations in UL97. Indicated in immunocompromised children (eg, HIV infection, posttransplant, other immunocompromised states) when clinical and virological evidence of specific end-organ disease (eg, pneumonitis, enteritis) is present.

In infants, antiviral therapy with ganciclovir may be of benefit in reducing the prevalence of neurodevelopmental sequelae, in particular sensorineural hearing loss (Schleiss, 2004). A study sponsored by the National Institutes of Allergy and Infectious Diseases demonstrated improved hearing-related outcomes in infants with symptomatic congenital CMV treated with ganciclovir (Kimberlin, 2003). Therefore, therapy in newborns with documented infection should be considered; however, consult an expert.

Cidofovir (Vistide)

Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Foscarnet (Foscavir)

Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases.

Class Summary

These agents are used as passive immunization for the prevention of symptomatic cytomegalovirus disease. This strategy has been useful in the control of cytomegalovirus disease in immunocompromised patients in the prenucleoside antiviral era. Evidence in pregnancy suggests that the infusion of cytomegalovirus immune globulin in women with evidence of a primary cytomegalovirus infection can prevent transmission and improve outcomes in newborns.

Immune globulin intravenous (Carimune, Gamimune, Gammagard S/D, Gammar-P, Polygam S/D)

The observation that random donor IVIG appears to be equal in efficacy to CMV hyperimmunoglobulin suggests that the benefit may be derived from an immunomodulatory effect unrelated to virus neutralization.

CMV-Ig (CytoGam)

A CMV hyperimmunoglobulin has been shown to decrease prevalence of CMV disease when administered posttransplant to high-risk transplant recipients when administered alone or in combination with nucleoside antivirals. May be administered therapeutically for CMV disease in combination with ganciclovir.