The development and implementation of stewardship initiatives to optimize the prevention and treatment of cytomegalovirus infection in solid-organ transplant recipients

2020 ◽  
Vol 41 (9) ◽  
pp. 1068-1074
Author(s):  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Lucas T. Schulz ◽  
Kerry A. Goldrosen ◽  
John P. Rice ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Organ Transplant ◽  
Immunocompromised Host ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Cmv Infection ◽  
Dual Approach ◽  
Optimal Outcomes ◽  
Prevention And Treatment ◽  
Individualization Of Therapy

AbstractClassical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function.

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Future Directions ◽  
Prevention And Treatment ◽  
Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

scholarly journals 1744. CMV Infection and Management Among Pediatric Solid-Organ Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S639-S639
Author(s):  
Anna Sharova ◽  
Despoina M Galetaki ◽  
Molly Hayes ◽  
Lauren Gianchetti ◽  
Laura A Vella ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Invasive Infection ◽  
Solid Organ ◽  
Cmv Infection ◽  
Research Support ◽  
Free Survival ◽  
Medium Risk ◽  
Cmv Disease

Abstract Background Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT. Methods Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests. Results 244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57). Conclusion CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

2000 ◽  
Vol 13 (1) ◽  
pp. 83-121 ◽  
Author(s):  
Irene G. Sia ◽  
Robin Patel
Keyword(s):  
Antiviral Agents ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Cmv Infection ◽  
Human Organ ◽  
Preventative Measures ◽  
Daunting Task ◽  
History Of ◽  
Antiviral Chemotherapy

SUMMARY In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

scholarly journals Safety of Valganciclovir Dosed 450 MG Three Times Weekly for Cytomegalovirus Prophylaxis in Solid Organ Transplant Recipients Requiring Hemodialysis

2021 ◽  
Author(s):  
Danielle Ecabert ◽  
Christine Pham ◽  
Brett J Pierce ◽  
William L Musick ◽  
Duc T Nguyen ◽  
...  
Keyword(s):  
Renal Function ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Severe Neutropenia ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Background Valganciclovir is the most commonly used antiviral for cytomegalovirus (CMV) prophylaxis in solid organ transplant recipients. However, there are limited clinical outcomes-supported data available to guide valganciclovir dosing in patients on hemodialysis (HD). This study aimed to assess the safety of our institution’s current dosing strategy of valganciclovir 450 mg three times weekly post-HD. Methods This was a single-center retrospective review of all adult non-kidney transplant recipients between May 2016 and June 2018. Patients with end stage renal disease requiring HD for >28 days post-transplant receiving valganciclovir 450 mg three times weekly post-HD were matched with non-HD patients receiving valganciclovir prophylaxis dosed per renal function. The primary endpoints were incidence of leukopenia, neutropenia, and thrombocytopenia while on valganciclovir prophylaxis. Results A total of 465 non-kidney transplants were performed during the study period, with 37 patients included in the HD group who were matched to 111 control patients in the non-HD group. Liver transplant recipients comprised 84% and 72% of each group, with none being CMV D+/R-. The rates of leukopenia (51.4% vs. 51.4%, p = 1.00), severe neutropenia (ANC <500 cells/µL, 15.8% vs. 14.0%, p = 0.85), and thrombocytopenia (24.3% vs. 20.7%, p = 0.64) were similar in both HD and non-HD groups. There were no cases of CMV infection while on valganciclovir prophylaxis in either group. Conclusions Valganciclovir 450 mg three times weekly was found to have similar rates of leukopenia, neutropenia, thrombocytopenia, and CMV infection in comparison to valganciclovir dosed per renal function in non-HD transplant recipients.

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