Abstract
Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Ganciclovir (GCV) and its prodrug valganciclovir are successfully used to prevent and treat CMV infection; however, in a small percentage of patients, CMV gene mutations may lead to drug resistance. GCV resistance is defined as increasing CMV viremia or progressive clinical disease during prolonged antiviral therapy, due to CMV gene mutation. This has emerged as a new challenge, especially because alternative drugs such as cidofovir and foscarnet have a number of important side effects. Here we report the case of a kidney transplanted patient who experienced life-threatening CMV disease, which initially appeared to be GCV-resistant, but was instead found to be associated with inadequate antiviral drug levels. The patient was then successfully treated by monitoring plasma GCV levels. We suggest using plasma GCV monitoring in the management of all cases of critical CMV disease, in which GCV resistance is suspected.
References
San Juan R, Aguado JM, Lumbreras C et al (2007) Incidence, clinical characteristics and risk factors of late infection in solid organ transplant recipients: data from the RESITRA study group. Am J Transpl 7(4):964–971
Rubin RH (1990) Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis 12(Suppl 7):S754–S766
Hibberd PL, Tolkoff-Rubin NE, Cosimi AB et al (1992) Simptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipient treated with OKT3. Transplantation 53(1):68–72
Lumbreras C, Otero JR, Herrero JA et al (1993) Ganciclovir prophylaxis decreases frequency and severity of cytomegalovirus disease in seropositive liver transplant recipients treated with OKT3 monoclonal antibodies. Antimicrob Agents Chemother 37(11):2490–2492
Hart GD, Paya CV (2001) Prophylaxis for CMV should now replace pre-emptive therapy in solid organ transplantation. Rev Med Virol 11(2):73–81
Emery VC (2001) Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation. Rev Med Virol 11(2):83–86
Brennan DC (2001) Cytomegalovirus in renal transplantation. J Am Soc Nephrol 12(4):848–855
Limaye AP, Corey L, Koelle DM et al (2000) Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet 19;356(9230):645–649
Nogueira E, Ozaki KS, Tomiyama H, Granato CF, Camara NO, Pacheco-Silva A (2006) The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients. Int Immunopharmacol 20;6(13–14): 2031–2037
Prichard MN, Kern ER (2011) The search for new therapies for human cytomegalovirus infections. Virus Res 157(2):212–221
Mendez JC, Sia IG, Tau KR et al (1999) Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy. Transplantation 67(5):755–757
Boivin G, Goyette N, Gilbert C et al (2005) Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol 77:425–429
Luck S, Lovering A, Griffiths P, Sharland M (2011) Ganciclovir treatment in children: evidence of subtherapeutic levels. Int J Antimicrob Agents 37(5):445–448
Kotton CN, Kumar D, Caliendo AM et al (2010) International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 89:779–795
Faulds D, Heel RC (1990) Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infection. Drugs 39:597–638
Lurain NS, Chou S (2010) Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23(4):689–712
Piketty C, Bardin C, Gilquin J et al (2000) Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis. Clin Microbiol Infect 6:117–120
Fishman JA, Doran MT, Volpicelli SH et al (2000) Dosing of intravenous ganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients. Transplantation 69:389–394
Tornatore KM, Garey KW, Saigal N et al (2001) Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection. Clin Transplant 15:297–308
Erice A, Jordan MC, Chace BA et al (1987) Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised host. JAMA 257:3082–3087
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Giulia Bedino and Pasquale Esposito equally contributed to this paper.
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Bedino, G., Esposito, P., Bosio, F. et al. The role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation. Int Urol Nephrol 45, 1809–1813 (2013). https://doi.org/10.1007/s11255-012-0293-y
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DOI: https://doi.org/10.1007/s11255-012-0293-y