Prophylaxis and treatment of cytomegalovirus disease in recipients of solid organ transplants: Current approach and future challenges

Current Opinion in Infectious Diseases

Volumn 20, Issue 4, 2007, Pages 419-424

  Puius, Yoram A ^a   Snydman, David R ^a  

^a TUFTS MEDICAL CENTER   (United States)

Author keywords

Antiviral therapy; Cytomegalovirus; Ganciclovir; Transplant; Valganciclovir

Indexed keywords

ACICLOVIR; ANTIVIRUS AGENT; GANCICLOVIR; IMMUNOGLOBULIN; PLACEBO; VALACICLOVIR; VALGANCICLOVIR;

ANTIVIRAL THERAPY; CLINICAL FEATURE; CLINICAL PRACTICE; COST BENEFIT ANALYSIS; COST EFFECTIVENESS ANALYSIS; CYTOMEGALOVIRUS INFECTION; HUMAN; INFECTION PREVENTION; LIVER GRAFT; ORGAN TRANSPLANTATION; POPULATION; PROPHYLAXIS; REVIEW; SURVIVAL;

ACYCLOVIR; ANTIVIRAL AGENTS; CLINICAL TRIALS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; DRUG RESISTANCE, VIRAL; GANCICLOVIR; HUMANS; IMMUNOGLOBULINS; ORGAN TRANSPLANTATION; POSTOPERATIVE COMPLICATIONS;

EID: 34347402281     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e32821f6026     Document Type: Review

References (33)

1. Snydman DR. The case for cytomegalovirus prophylaxis in solid organ transplantation. Rev Med Virol 2006; 16:289-295.
2. Gane E, Saliba F, Valdecasas GJ, et al. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected]. Lancet 1997; 350:1729-1733.
3. Koetz AC, Delbruck R, Furtwangler A, et al. Cytomegalovirus pp65 antigen-guided preemptive therapy with ganciclovir in solid organ transplant recipients: a prospective, double-blind, placebo-controlled study. Transplantation 2001; 72:1325-1327.
4. Singh N, Paterson DL, Gayowski T, et al. Cytomegalovirus antigenemia directed preemptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial. Transplantation 2000; 70:717-722.
5. Hibberd PL, Tolkoff-Rubin NE, Conti D, et al. Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. A randomized controlled trial. Ann Intern Med 1995; 123:18-26.
6. Singh N. Late-onset cytomegalovirus disease as a significant complication in solid organ transplant recipients receiving antiviral prophylaxis: a call to heed the mounting evidence. Clin Infect Dis 2005; 40:704-708.
7. Snydman DR. Counterpoint: prevention of cytomegalovirus (CMV) infection and CMV disease in recipients of solid organ transplants: the case for prophylaxis. Clin Infect Dis 2005; 40:709-712.
8. Singh N. Antiviral drugs for cytomegalovirus in transplant recipients: advantages of preemptive therapy. Rev Med Virol 2006; 16:281-287.
9. Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet 2005; 365:2105-2115.
10. Strippoli GF, Hodson EM, Jones C, Craig JC. Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation 2006; 81:139-145. The investigators pooled a number of trials involving preemptive therapy, including six RCTs including 288 patients, comparing preemption to standard care, where the benefit was clearest in prevention of CMV disease. A sub-analysis also compared preemption to prophylaxis.
11. 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; 43:869-880. This large meta-analysis compared outcomes from 17 prophylaxis trials containing 1560 subjects against nine preemption trials containing 457 subjects, showing no clear difference in outcomes.
12. Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 2005; 143:870-880.
13. Jung C, Engelmann E, Borner K, Offermann G. Preemptive oral ganciclovir therapy versus prophylaxis to prevent symptomatic cytomegalovirus infection after kidney transplantation. Transplant Proc 2001; 33:3621-3623.
14. Khoury JA, Storch GA, Bohl DL, et al. Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients. Am J Transplant 2006; 6:2134-2143. This study demonstrated similar outcomes and cost-effectiveness in renal transplant patients receiving VGCV-based preemptive or prophylactic regimens.
15. Legendre C, Beard SM, Crochard A, et al. The cost-effectiveness of prophylaxis with valaciclovir in the management of cytomegalovirus after renal transplantation. Eur J Health Econ 2005; Mar 12 [Epub ahead of print].
16. Reischig T, Opatrny K Jr, Treska V, et al. Prospective comparison of valacyclovir and oral ganciclovir for prevention of cytomegalovirus disease in high-risk renal transplant recipients. Kidney Blood Press Res 2005; 28:218-225.
17. Limaye AP, Bakthavatsalam R, Kim HW, et al. Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis. Transplantation 2006; 81:1645-1652. This retrospective analysis of outcomes in 437 liver transplant recipients used targeted GCV or VGCV prophylaxis in high-risk patients, VACV for others, with favorable results.
18. Diaz-Pedroche C, Lumbreras C, San Juan R, et al. Valganciclovir preemptive therapy for the prevention of cytomegalovirus disease in high-risk seropositive solid-organ transplant recipients. Transplantation 2006; 82:30-35. This combination of targeted prophylaxis with VGCV in high-risk patients, with VACV for donor seronegative/recipient seronegative cases, showed a low incidence of CMV disease in a commonly employed regimen.
19. Park JM, Lake KD, Arenas JD, Fontana RJ. Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients. Liver Transpl 2006; 12:112-116. In liver SOT recipients, prophylaxis with half-dose VGCV has similar outcomes to standard-dose oral GCV, suggesting the possibility of using lower doses of VGCV.
20. •], prophylaxis with half-dose VGCV has similar outcomes to standard-dose oral GCV in renal and pancreas SOT recipients as well.
21. Doron S, Ruthazer R, Werner BG, et al. Hypogammaglobulinemia in liver transplant recipients: incidence, timing, risk factors, and outcomes. Transplantation 2006; 81:697-703.
22. Yip NH, Lederer DJ, Kawut SM, et al. Immunoglobulin G levels before and after lung transplantation. Am J Respir Crit Care Med 2006; 173:917-921.
23. Ruttmann E, Geltner C, Bucher B, et al. Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Transplantation 2006; 81:1415-1420.
24. Potena L, Holweg CT, Chin C, et al. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation 2006; 82:398-405.
25. Razonable RR. Epidemiology of cytomegalovirus disease in solid organ and hematopoietic stem cell transplant recipients. Am J Health Syst Pharm 2005; 62:S7-S13.
26. Kijpittayarit S, Deziel P, Eid AJ, Razonable RR. Primary cytomegalovirus disease after five years of antiviral prophylaxis. Transplantation 2006; 81:137-138.
27. Kuypers DR, Claes K, Evenepoel P, et al. A simplified strategy for clinical management of late cytomegalovirus infection after oral ganciclovir prophylaxis in renal recipients. J Antimicrob Chemother 2005; 55:391-394.
28. Doyle AM, Warburton KM, Goral S, et al. 24-week oral ganciclovir prophylaxis in kidney recipients is associated with reduced symptomatic cytomegalovirus disease compared to a 12-week course. Transplantation 2006; 81:1106-1111. This is the first head-to-head comparison of 24 versus 12 weeks of prophylaxis, demonstrating long-term benefit for the longer course.
29. Singh N, Wannstedt C, Keyes L, et al. Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus disease. Transplantation 2005; 79:85-90.
30. Boivin G, Goyette N, Gilbert C, et al. Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients. J Infect Dis 2004; 189:1615-1618.
31. Nogueira E, Ozaki KS, Tomiyama H, et al. The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients. Int Immunopharmacol 2006; 6:2031-2037.
32. Boivin G, Goyette N, Gilbert C, et al. Clinical impact of ganciclovir-resistant cytomegalovirus infections in solid organ transplant patients. Transpl Infect Dis 2005; 7:166-170.
33. Chen F, Bando T, Hanaoka N, et al. Early onset of ganciclovir-resistant cytomegalovirus infection in a lung-transplant recipient. Jpn J Thorac Cardiovasc Surg 2005; 53:562-564.