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Development of resistance in cytomegalovirus infection in a newborn: case report A male neonate developed resistance to ganciclovir and valganciclovir during treatment for congenital cytomegalovirus (CMV) infection. The boy’s mother had an unrecognised primary CMV infection, and gave birth to a congenitally infected boy at 33 weeks gestation. The boy had intrauterine growth retardation, intracerebral calcifications, ventriculomegaly, neuromotor disabilities, microcefalia, hepatitis, hepatosplenomegaly, petechiae and thrombocytopenia. On the first day of life, tests revealed positive CMV antigenaemia and DNAemia, and the boy was diagnosed with a CMV congenital infection. On the second day of life, he received IV ganciclovir 6 mg/kg twice a day. On day 13, he developed neutropenia, and ganciclovir was discontinued. He subsequently deteriorated clinically, and started valganciclovir 5 mg/kg twice a day on day 37, which was progressively increased to a dosage of 15 mg/kg twice a day [route not stated]. Despite administration of valganciclovir, there was no clinical improvement or reduction in blood viral road. After 25 days of valganciclovir treatment, a brainstem-evoked response audiometry revealed a bilateral transmission delay. On day 112, valganciclovir was switched to IV ganciclovir 6 mg/kg twice a day for 1 week; however, he did not improve clinically or virologically. He was admitted, and examination additionally revealed respiratory distress and bilateral chorioretinitis. He received oxygen for respiratory distress, and daily platelet transfusions for thrombocytopenia. Ganciclovir and valganciclovir resistance was suspected, and genotyping of blood samples taken from day 113 revealed a mixture of CMV strains with M460V, C592G and A594V mutations in the UL97 gene responsible for ganciclovir and valganciclovir resistance. On day 127, he started foscarnet. He improved clinically, with a reduction of CMV DNA levels in blood. On day 173, foscarnet was discontinued. On day 203, his blood CMV DNA level remained high. He died at 8 months of age due to pulmonary complications. Author comment: "[T]he emergence of [CMV] drugresistance in symptomatic congenital infections chronically treated with [ganciclovir] or [valganciclovir] should be taken into account". Campanini G, et al. Multiple ganciclovir-resistant strains in a newborn with symptomatic congenital human cytomegalovirus infection. Journal of Clinical Virology 54: 86-88, No. 1, May 2012. Available from: URL: http:// 803075858 dx.doi.org/10.1016/j.jcv.2012.01.020 - Italy

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Reactions 25 Aug 2012 No. 1416