Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: Implications for the emergence of drug-resistant cytomegalovirus

Tiziano Allice, Alessandro Busca, Franco Locatelli, Michele Falda, Fabrizia Pittaluga, Valeria Ghisetti

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objectives: Valganciclovir is a well established drug for the management of cytomegalovirus (CMV) infection in haematopoietic stem cell transplantation (HSCT). Data concerning its safety regarding the development of drug resistance are required. The aim of the present study was to retrospectively investigate CMV drug resistance in a group of HSCT patients experiencing relapses of CMV infection after a first-line pre-emptive antiviral therapy. Methods: Thirteen adult HSCT patients out of 26 with asymptomatic CMV infection, experiencing relapsing infections 45-155 days after either intravenous (iv) ganciclovir (2 patients) or valganciclovir (11 patients), were studied. Genotypic assays for mutations in the viral phosphotransferase (UL97) and DNA-polymerase (UL54) genes were directly applied on patient specimens. Baseline CMV sequences were compared with those at the time of relapses to identify drug-resistant strains. Results: UL97 mutations A594V and M460V known to confer drug resistance developed in one relapsing patient who received iv ganciclovir as first-line therapy, corresponding to a rate of 7.7% of relapses due to drug-resistant strains and an overall 3.8% rate of infections due to CMV drug-resistant strains. UL54 drug resistance mutations were absent. No evidence of drug resistance was found in patients on valganciclovir either as first-line therapy or as treatment for relapses. Conclusions: The safety profile of valganciclovir as anti-CMV pre-emptive therapy was confirmed, as well as that monitoring CMV drug resistance with genotypic tests on sequential isolates over the time-course of therapy offers guidance to tailor antiviral treatment in a clinically relevant time frame.

Original languageEnglish
Pages (from-to)600-608
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume63
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Cytomegalovirus Infections
Stem Cell Transplantation
Cytomegalovirus
Drug Resistance
Hematopoietic Stem Cell Transplantation
Pharmaceutical Preparations
Recurrence
Ganciclovir
Mutation
Therapeutics
Antiviral Agents
Safety
Asymptomatic Infections
Adult Stem Cells
DNA-Directed DNA Polymerase
Infection
valganciclovir
Phosphotransferases
Genes

Keywords

  • CMV
  • Mutations
  • Sequences
  • UL54
  • UL97

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation : Implications for the emergence of drug-resistant cytomegalovirus. / Allice, Tiziano; Busca, Alessandro; Locatelli, Franco; Falda, Michele; Pittaluga, Fabrizia; Ghisetti, Valeria.

In: Journal of Antimicrobial Chemotherapy, Vol. 63, No. 3, 2009, p. 600-608.

Research output: Contribution to journalArticle

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abstract = "Objectives: Valganciclovir is a well established drug for the management of cytomegalovirus (CMV) infection in haematopoietic stem cell transplantation (HSCT). Data concerning its safety regarding the development of drug resistance are required. The aim of the present study was to retrospectively investigate CMV drug resistance in a group of HSCT patients experiencing relapses of CMV infection after a first-line pre-emptive antiviral therapy. Methods: Thirteen adult HSCT patients out of 26 with asymptomatic CMV infection, experiencing relapsing infections 45-155 days after either intravenous (iv) ganciclovir (2 patients) or valganciclovir (11 patients), were studied. Genotypic assays for mutations in the viral phosphotransferase (UL97) and DNA-polymerase (UL54) genes were directly applied on patient specimens. Baseline CMV sequences were compared with those at the time of relapses to identify drug-resistant strains. Results: UL97 mutations A594V and M460V known to confer drug resistance developed in one relapsing patient who received iv ganciclovir as first-line therapy, corresponding to a rate of 7.7{\%} of relapses due to drug-resistant strains and an overall 3.8{\%} rate of infections due to CMV drug-resistant strains. UL54 drug resistance mutations were absent. No evidence of drug resistance was found in patients on valganciclovir either as first-line therapy or as treatment for relapses. Conclusions: The safety profile of valganciclovir as anti-CMV pre-emptive therapy was confirmed, as well as that monitoring CMV drug resistance with genotypic tests on sequential isolates over the time-course of therapy offers guidance to tailor antiviral treatment in a clinically relevant time frame.",
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