Ganciclovir treatment failure in adult allogeneic hematopoietic stem cell transplant recipients with cytomegalovirus infection – a single centre experience
Authors:
E. Vejražková 1; P. Hubáček 2; R. Kutová 3; L. Plíšková 3; M. Košťál 1; V. Štěpánová 4; A. Zavřelová 1; J. Radocha 1; E. Malá 5; P. Žák 1
Authors place of work:
IV. interní hematologická klinika, Fakultní nemocnice v Hradci Králové a Lékařská fakulta v Hradci Králové Univerzity Karlovy v Praze
1; Klinika dětské hematologie a onkologie a Ústav lékařské mikrobiologie, Fakultní nemocnice v Motole a 2. lékařská fakulta Univerzity Karlovy v Praze
2; Ústav klinické biochemie a diagnostiky, Fakultní nemocnice v Hradci Králové a Lékařská fakulta v Hradci Králové Univerzity Karlovy v Praze
3; Ústav klinické mikrobiologie, Fakultní nemocnice v Hradci Králové a Lékařská fakulta v Hradci Králové Univerzity Karlovy v Praze
4; Ústav klinické imunologie a alergologie, Fakultní nemocnice v Hradci Králové a Lékařská fakulta v Hradci Králové Univerzity Karlovy v Praze
5
Published in the journal:
Epidemiol. Mikrobiol. Imunol. 64, 2015, č. 3, s. 160-168
Category:
Original Papers
Summary
Objective:
To determine the incidence of infection with ganciclovir-resistant cytomegalovirus (CMV) in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. Clinical resistance or treatment failure was defined as persistent DNAemia or increasing viral load in peripheral blood after 2 weeks of virostatic treatment. The association between the treatment failure and viral resistance was analysed. The presence of ganciclovir – resistant CMV strains was confirmed by genotypic testing able to detect mutations conferring resistance.
Methods:
In 2012 and 2014, 40 patients who underwent allogeneic HSCT for hematologic malignancies and were treated for human CMV reactivation/disease were followed up prospectively. In patients with treatment failure, CMV DNA was isolated and analysed by nucleotide sequence analysis of the UL 97 and UL 54 genes conferring resistance to the virostatic agent.
Results:
The treatment failure occurred in seven patients, but ganciclovir resistance conferring mutations were only detected in two of them (mutations L595F and M460I in the UL 97 gene). Another mutation in the UL 97 gene (N510S) was found in a patient with recurrent CMV replication who needed to be retreated but did not meet the criteria for treatment failure.
Conclusion:
The low incidence of genetically confirmed ganciclovir-resistant CMV isolates in HSCT recipients with relatively common clinical treatment failure suggests that the mechanism underlying slower viral clearance is often other than mutations conferring ganciclovir resistance to the virus.
Key words:
human cytomegalovirus – ganciclovir – valganciclovir – viral resistance – hematopoietic stem cell transplantation
Zdroje
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Štítky
Hygiene and epidemiology Medical virology Clinical microbiologyČlánok vyšiel v časopise
Epidemiology, Microbiology, Immunology
2015 Číslo 3
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