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

Beatriz Morillo-Gutierrez,Sheila Waugh,Marieke Emonts,Terence Flood,Ailsa Pickering

doi:10.1186/s12887-017-0933-6

Beatriz Morillo-Gutierrez, Sheila Waugh + Show 3 more

Open Access

https://doi.org/10.1186/s12887-017-0933-6

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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.

Highlights

Congenital cytomegalovirus infection is an important illness that is a common cause of hearing loss in newborn infants and a major cause of disability in children
The fourth case was described by Choi et al [7], in a patient who developedganciclovir resistance noted as an increment in viraemia with no associated symptoms; the viraemia cleared after stopping the treatment
She does not require hearing aids, and she is vocalising, but uses no single words. She developed severe epilepsy at about 2 years of life. To date, this is the fifth case of Congenital cytomegalovirus (cCMV) resistant to ganciclovir described in the literature while on treatment

Summary

Conclusions

This is the fifth case of cCMV resistant to ganciclovir described in the literature while on treatment. We postulate that the rise in the viral load due to the resistance resulted in an increased immune stimulus to CMV, acting as a boost to immunity and, subsequently, a fall in the viral load This case adds another example of cCMV and highlights the importance of frequent monitoring to detect resistant strains, as well as adverse effects related to treatment. As treatment for symptomatic cCMV has been recommended with (val)ganciclovir (1), the emergence of resistance mutations is a potential risk given the combination of high viral loads, prolonged treatment, and the potential for suboptimal drug levels even with dose increments in newborns and infants [8,9,10]. Endnotes 1After the introduction of the recommendations of (val)ganciclovir treatment for symptomatic congenital CMV, surveillance with periodic viral loads and drug monitoring are vital to identify emerging resistance and optimise antiviral dosing in line with weight gain

Background

Findings

Funding None