LOW SYSTEMIC GANCICLOVIR EXPOSURE AND PREEMPTIVE TREATMENT FAILURE OF CYTOMEGALOVIRUS REACTIVATION IN A TRANSPLANTED CHILD
Main Article Content
Keywords
Cytomegalovirus, pediatric, pharmacokinetic, ganciclovir, resistance
Abstract
Prevention of cytomegalovirus (CMV) disease with ganciclovir has led to decrease morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. In the present report, we describe a case of ganciclovir treatment failure in a HSCT child who presented a refractory CMV infection despite harbouring a susceptible strain. The failure was partly attributed to sub-therapeutic plasma ganciclovir levels. Our experience emphasizes the importance of drug monitoring in immunocompromised patients.
References
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2. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009;113(23):5711-9.
3. Albano MS, Taylor P, Pass RF, et al. Umbilical cord blood transplantation and cytomegalovirus: Posttransplantation infection and donor screening. Blood 2006;108(13):4275-82.
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5. Small LN, Lau J, Snydman DR. Preventing postorgan transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies. Clin Infect Dis 2006;43(7):869-80.
6. Meijer E, Boland GJ, Verdonck LF. Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants. Clin Microbiol Rev 2003;16(4):647-57.
7. Eckle T, Prix L, Jahn G, et al. Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood 2000;96(9):3286-9.
8. Boivin G, Chou S, Quirk MR, Erice A, Jordan MC. Detection of ganciclovir resistance mutations quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. J Infect Dis 1996;173(3):523-8.
9. Zhang D, Lapeyraque AL, Popon M, Loirat C, Jacqz-Aigrain E. Pharmacokinetics of ganciclovir in paediatric renal transplant recipients. Pediatr Nephrol 2003;18(9):943-8.
10. Erice A, Borrell N, Li W, Miller WJ, Balfour HH, Jr. Ganciclovir susceptibilities and analysis of UL97 region in cytomegalovirus (CMV) isolates from bone marrow recipients with CMV disease after antiviral prophylaxis. J Infect Dis 1998;178(2):531-4.
11. Boivin G, Gilbert C, Morissette M, Handfield J, Goyette N, Bergeron MG. A case of ganciclovirresistant cytomegalovirus (CMV) retinitis in a patient with AIDS: longitudinal molecular analysis of the CMV viral load and viral mutations in blood compartments. AIDS 1997;11(7):867-73.
12. Reusser P, Einsele H, Lee J, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 2002;99(4):1159-64.
13. Gilbert C, Boivin G. Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother 2005;49(3):873-83.
14. Faulds D, Heels R. Ganciclovir: a review of its antiviral activities, pharmacokinetic properties and therapeutic efficacy cytomegalovirus infections. Drugs 1990;39:597-638.
15. Fletcher C, Sawchuk R, Chinnock B, Miranda P, Balfour HH. Human pharmacokinetics for the antiviral drug DHPG. Clin Parmacol Ther 1986;40: 281-6.
16. Piketty C, Bardin C, Gilquin J, Gairard A, Kazatchkine MD, Chast F. Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis. Clin Microbiol Infect 2000;6(3):117-20.
17. Wiltshire H, Paya CV, Pescovitz MD, et al. Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation 2005;79(11):1477-83.
18. Vethamuthu J, Feber J, Chretien A, Lampe D, Filler G. Unexpectedly high inter- and intrapatient variability of ganciclovir levels in children. Pediatr Transplant 2007;11(3):301-5.
2. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009;113(23):5711-9.
3. Albano MS, Taylor P, Pass RF, et al. Umbilical cord blood transplantation and cytomegalovirus: Posttransplantation infection and donor screening. Blood 2006;108(13):4275-82.
4. Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers JD. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med 1993;118(3): 173-8.
5. Small LN, Lau J, Snydman DR. Preventing postorgan transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies. Clin Infect Dis 2006;43(7):869-80.
6. Meijer E, Boland GJ, Verdonck LF. Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants. Clin Microbiol Rev 2003;16(4):647-57.
7. Eckle T, Prix L, Jahn G, et al. Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood 2000;96(9):3286-9.
8. Boivin G, Chou S, Quirk MR, Erice A, Jordan MC. Detection of ganciclovir resistance mutations quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. J Infect Dis 1996;173(3):523-8.
9. Zhang D, Lapeyraque AL, Popon M, Loirat C, Jacqz-Aigrain E. Pharmacokinetics of ganciclovir in paediatric renal transplant recipients. Pediatr Nephrol 2003;18(9):943-8.
10. Erice A, Borrell N, Li W, Miller WJ, Balfour HH, Jr. Ganciclovir susceptibilities and analysis of UL97 region in cytomegalovirus (CMV) isolates from bone marrow recipients with CMV disease after antiviral prophylaxis. J Infect Dis 1998;178(2):531-4.
11. Boivin G, Gilbert C, Morissette M, Handfield J, Goyette N, Bergeron MG. A case of ganciclovirresistant cytomegalovirus (CMV) retinitis in a patient with AIDS: longitudinal molecular analysis of the CMV viral load and viral mutations in blood compartments. AIDS 1997;11(7):867-73.
12. Reusser P, Einsele H, Lee J, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 2002;99(4):1159-64.
13. Gilbert C, Boivin G. Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother 2005;49(3):873-83.
14. Faulds D, Heels R. Ganciclovir: a review of its antiviral activities, pharmacokinetic properties and therapeutic efficacy cytomegalovirus infections. Drugs 1990;39:597-638.
15. Fletcher C, Sawchuk R, Chinnock B, Miranda P, Balfour HH. Human pharmacokinetics for the antiviral drug DHPG. Clin Parmacol Ther 1986;40: 281-6.
16. Piketty C, Bardin C, Gilquin J, Gairard A, Kazatchkine MD, Chast F. Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis. Clin Microbiol Infect 2000;6(3):117-20.
17. Wiltshire H, Paya CV, Pescovitz MD, et al. Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation 2005;79(11):1477-83.
18. Vethamuthu J, Feber J, Chretien A, Lampe D, Filler G. Unexpectedly high inter- and intrapatient variability of ganciclovir levels in children. Pediatr Transplant 2007;11(3):301-5.