Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir

Abstract

Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation. Earlier studies showed that 6-weeks' treatment with ganciclovir, starting in the neonatal period, prevented hearing deterioration at 6 months, but in one-fifth of the infants, the effect was not sustained at age 12 months. The aim of this preliminary retrospective study was to investigate the effectiveness and safety of long-term treatment with ganciclovir/valganciclovir for congenital cytomegalovirus infection. Twenty-three infants with culture-proven symptomatic congenital cytomegalovirus infection were treated with ganciclovir for 6 weeks followed by oral valganciclovir to age 12 months. Audiometry was performed at least three times in the first year, in addition to physical examination including neurological and developmental assessment. At age >or=1 year, hearing was normal in 76% of affected ears compared to baseline (54%). In 25 normal ears at birth no deterioration was found at >or=1 year. These results were significantly better than reported in a historical control group of similar infants treated for 6 weeks only (P= 0.001). Viral load monitoring demonstrated sustained virological response. Four of the children (18%) had mental retardation. The main side effect of treatment was transient neutropenia. In conclusion, prolonged therapy of symptomatic congenital CMV infection with intravenous ganciclovir followed by oral valganciclovir is safe, and it appears to lead to a better auditory outcome than short-term treatment.

Hearing Loss and Congenital CMV Infection: A Systematic Review

“…Currently, antiviral treatment with ganciclovir or valganciclovir is recommended only for symptomatic newborns with severe symptomatic focal organ disease or central nervous system involvement. [109][110][111][112] The remainder could be enrolled in a longitudinal follow-up program to detect delayed-onset or progressive hearing loss and other developmental delays. Early detection of hearing loss leads to early intervention and better patient outcomes.…”

Valganciclovir for Symptomatic Congenital Cytomegalovirus Disease

“…13 Other reports in the literature involve individual cases [20][21][22][23][24] or small, uncontrolled case series. [25][26][27] The earlier randomized, controlled trial showed a benefit of 6 weeks of parenteral ganciclovir therapy with respect to best-ear hearing from baseline to 6 months, but there was a suggestion that this benefit wanes over the first 2 years of life. 13 On the basis of these data, the change in best-ear hearing from baseline to 6 months was selected as the primary end point of this trial.…”

Antiviral Drug Resistance of Human Cytomegalovirus

“…GCV has been used to treat congenital infections (2,35,147,204). A randomized controlled trial of a 6-week course of intravenous GCV therapy in symptomatic neonates showed significantly improved hearing at follow-up (110).…”

“…A randomized controlled trial of a 6-week course of intravenous GCV therapy in symptomatic neonates showed significantly improved hearing at follow-up (110). Other small studies have found the use of GCV therapy for congenital infections to be effective in reducing hearing loss (2,147,158), although there remain concerns regarding GCV toxicity, mainly myelosuppression, and optimal treatment regimens have not been established.…”