Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis

Therapeutic implications and outcomes

Albert J. Eid, Supha K. Arthurs, Paul J. Deziel, Mark P. Wilhelm, Raymund R Razonable

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Background: Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis. Methods: The medical records of all CMV D+/R-kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed.: During a four-yr-study period, a total of 225 CMV D+/R-transplant patients received valganciclovir prophylaxis for a median of 92d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV. Conclusions: Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.

Original languageEnglish (US)
Pages (from-to)162-170
Number of pages9
JournalClinical Transplantation
Volume22
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Cytomegalovirus
Pharmaceutical Preparations
Therapeutics
valganciclovir
Transplants
Allografts
Foscarnet
Ganciclovir
Mortality
Incidence
Organ Transplantation
Immunosuppression
Medical Records
Pancreas

Keywords

  • Acute renal failure
  • Allograft failure
  • Foscarnet
  • Mortality
  • Pancreas transplant

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis : Therapeutic implications and outcomes. / Eid, Albert J.; Arthurs, Supha K.; Deziel, Paul J.; Wilhelm, Mark P.; Razonable, Raymund R.

In: Clinical Transplantation, Vol. 22, No. 2, 03.2008, p. 162-170.

Research output: Contribution to journalArticle

Eid, Albert J. ; Arthurs, Supha K. ; Deziel, Paul J. ; Wilhelm, Mark P. ; Razonable, Raymund R. / Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis : Therapeutic implications and outcomes. In: Clinical Transplantation. 2008 ; Vol. 22, No. 2. pp. 162-170.
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abstract = "Background: Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis. Methods: The medical records of all CMV D+/R-kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed.: During a four-yr-study period, a total of 225 CMV D+/R-transplant patients received valganciclovir prophylaxis for a median of 92d. Sixty-five (29{\%}) of the 225 patients developed delayed-onset primary CMV disease, including nine (14{\%}) suspected to have drug-resistant virus. Four (6.2{\%}) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV. Conclusions: Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.",
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