Emerging (val)ganciclovir resistance during treatment of congenital CMV infection: a case report and review of the literature

Abstract

BackgroundCongenital cytomegalovirus (cCMV) infection is an important illness that is a common cause of hearing loss in newborn infants and a major cause of disability in children. For that reason, treatment of symptomatic patients with either ganciclovir or its pro-drug valganciclovir is recommended. Treatment duration of 6 months has been shown to be more beneficial than shorter courses; however, there is uncertainty regarding emergence of resistance strains, secondary effects and long term sequelae.Case presentationHere we present a female infant with symptomatic cCMV who was treated from day 5 of life with oral valganciclovir. In spite of close monitoring of her drug levels and increments of her treatment dose according to weight gain, she developed ganciclovir resistance after 4 months of treatment, with increasing viraemia and petechiae. Adherence to treatment was assessed and felt to be good. Clinically, although she had marked developmental delay, she was making steady progress. In view of the development of resistance treatment was stopped at 5 months of age. No secondary effects of ganciclovir were noted during the whole course.ConclusionsThere were few cases in the literature reporting resistance to ganciclovir for cCMV before the new recommendations for a 6 months treatment course for this infection were published. As demonstrated in our patient, surveillance with periodic viral loads and drug monitoring are vital to identify emerging resistance and optimise antiviral dosing according to weight gain.

Onset of valganciclovir resistance in two infants with congenital cytomegalovirus infection

“…The second child (case 2) reported a modest developmental delay. We agree with other authors (Campanini et al, 2012;Benzi et al, 2012;Choi et al, 2013;Morillo-Gutierrez et al, 2017) that a prolonged therapeutic exposure may be a risk factor for resistance in cCMV patients, and thus viral load surveillance is the key in monitoring early onset of resistance to V-GCV/GCV. Time-scheduled viral load assessments allow prompt identification of resistance, avoiding ineffective therapy and related ADs, even if the current literature mainly indicates that long-term therapy, after the initial period, does not account for ADs while ongoing (Amir et al, 2010;James and Kimberlin, 2016).…”

Congenital Cytomegalovirus Pneumonitis and Treatment Response Evaluation Using Viral Load during Ganciclovir Therapy: a Case Report

“…The benefit of measurement of CMV genome load in treatment for congenital CMV infection has not been well reported. Morillo-Gutierrez et al (15) reported that periodic viral load testing is important to identify emerging resistance strains of CMV during antiviral therapy. In the present case, intravenous ganciclovir therapy appeared to be clinically effective.…”

Design, Synthesis, and Preliminary Studies of Spiro-isoxazoline-peroxides against Human Cytomegalovirus and Glioblastoma

“…The compounds 13f and 13k showed virus inhibition in this assay; however, much more concentration is required that may be impractical to attain physiologically. Considering widespread resistance against GCV in clinical strains of HCMV and well-known side effects such as neutropenia, compound 13m exhibited a moderate activity (IC 50 = 19 μM), which could lead to future drug discovery for HCMV. − …”