Despite recent advances, cytomegalovirus (CMV) infections remain one of the most common complications affecting solid organ transplant recipients, conveying higher risks of complications, graft loss, morbidity, and mortality. Research in the field and development of prior consensus guidelines supported by The Transplantation Society has allowed a more standardized approach to CMV management. An international multidisciplinary panel of experts was convened to expand and revise evidence and expert opinion-based consensus guidelines on CMV management including prevention, treatment, diagnostics, immunology, drug resistance, and pediatric issues. Highlights include advances in molecular and immunologic diagnostics, improved understanding of diagnostic thresholds, optimized methods of prevention, advances in the use of novel antiviral therapies and certain immunosuppressive agents, and more savvy approaches to treatment resistant/refractory disease. The following report summarizes the updated recommendations.
Cytomegalovirus (CMV) continues to be one of the most common infections after solid-organ transplantation, resulting in significant morbidity, graft loss, and adverse outcomes. Management of CMV varies considerably among transplant centers but has been become more standardized by publication of consensus guidelines by the Infectious Diseases Section of The Transplantation Society. An international panel of experts was reconvened in October 2012 to revise and expand evidence and expert opinion-based consensus guidelines on CMV management, including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues. The following report summarizes the recommendations.
We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R-patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigatortreated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p = 0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, oncedaily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.
Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence‐based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug‐resistant CMV infection are presented. There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.
Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.
Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.
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