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JAC Advance Access originally published online on March 14, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):862-867; doi:10.1093/jac/dkp083
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Reviews

Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies

Lauren Nassetta1, David Kimberlin1 and Richard Whitley1,2,*

1 Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA 2 Departments of Medicine, Microbiology and Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA

* Corresponding author. E-mail: Rwhitley{at}peds.uab.edu

Cytomegalovirus (CMV) infection is the most common cause of congenital infection in the developed world, occurring in ~1% of all liveborns. Symptomatic disease occurs in 10% of all congenitally infected infants, resulting in a spectrum of clinical manifestations that include microcephaly, chorioretinitis, hepatosplenomegaly and sensorineural hearing loss, among others. Even those children who are asymptomatic at birth have a risk of hearing loss, with ~8% experiencing this sequela. Overall, congenital CMV infection accounts for one-third of all cases of sensorineural hearing loss. The economic burden of disease exceeds $2 billion annually in the USA. Therefore, this infection has been the target for antiviral therapy. Studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (CASG) have evaluated ganciclovir for the treatment of symptomatic congenital CMV infection with central nervous system involvement. In a randomized, controlled clinical trial of ganciclovir treatment (6 mg/kg iv every 12 h for 6 weeks) brainstem-evoked responses were utilized as the primary endpoint and demonstrated stabilization of hearing both at 6 months and >1 year. Treatment was associated with neutropenia in over 60% of treated patients. Since ganciclovir must be given intravenously, studies with its prodrug, valganciclovir, have been performed to assess pharmacokinetics and pharmacodynamics. Currently, a clinical trial of 6 weeks versus 6 months of valganciclovir is being performed by the CASG. Notably, only intravenous ganciclovir and orally administered valganciclovir have been used to treat congenital CMV infection. Hopefully, other drugs such as maribavir will be available for evaluation in this population.

Keywords: congenital infection , therapy , CMV


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