|
Basic Characteristics of Mutations
|
|
Mutation Site
|
H602Y |
|
Mutation Site Sentence
|
A new mutation (H602Y, patient ID #13), identified by comparing CMV UL97 sequences from our study with UL97 sequences from both laboratory and clinical isolates in GenBank [n = 77, see Supplementary data, available at JAC Online (http://jac.oxfordjournals.org/)], which has never been described as associated with CMV drug resistance, developed in a patient who received a regular course of valganciclovir as first-line treatment (CMV DNA became negative after 10 days of treatment). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
UL97 |
|
Standardized Encoding Gene
|
UL97
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
BK000394;X17403
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cytomegalovirus infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
19147520
|
|
Title
|
Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus
|
|
Author
|
Allice T,Busca A,Locatelli F,Falda M,Pittaluga F,Ghisetti V
|
|
Journal
|
The Journal of antimicrobial chemotherapy
|
|
Journal Info
|
2009 Mar;63(3):600-8
|
|
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.
|
|
Sequence Data
|
-
|