Cytomegalovirus antiviral stewardship in solid organ transplant recipients: A new gold standard

Abstract

Purpose Antimicrobial stewardship programs (ASPs) are essential entities that promote the appropriate use of antimicrobials, leading to improved patient outcomes and reduced resistance. Application to the immunocompromised host is a natural progression for expansion. Cytomegalovirus (CMV) infection is a common complication following solid organ transplant with significant implications on graft survival, making it an attractive ASP target. The aim of this piece is to review our center‐specific experience with the development, implementation, and maintenance of a CMV stewardship initiative at a large transplant center. Methods Our CMV stewardship initiative began in 2018. Herein, we review 3 years’ experience and quality‐related improvement that occurred from initiation to present state and share our stewardship algorithms. Special attention is paid to the impact of the program as well as our increased understanding of the complex interplay between prevention, treatment, and host development of CMV‐specific cell‐mediated immunity (CMI). Results We found our stewardship initiative not only reduced the incidence of ganciclovir resistance but also streamlined care via a centralized and structured approach. This objective, protocolized program has resulted in a significant shift away from a reactive to a proactive state and in turn, reduced CMV treatment rates (26% at initiation to 12% in the current state, p = .012). Conclusion A dedicated multidisciplinary team focused on CMV stewardship is imperative in providing a patient‐centered approach focused on development of CMV‐specific CMI, and as a result prevention of CMV disease. We believe these programs will be the new gold standard for CMV management.

Challenges and Opportunities in Antimicrobial Stewardship among Hematopoietic Stem Cell Transplant and Oncology Patients

“…Notably, these antivirals have adverse effects: foscarnet and cidofovir can cause nephrotoxicity, while maribavir can interact with CYP3A4 substrates resulting in increased tacrolimus concentrations [ 69 , 70 ]. Publications by Jorgenson et al describe a pharmacy-directed approach to CMV antiviral stewardship in SOT programs that has been associated with a decrease in the number of patients requiring treatment and a reduced ganciclovir resistance rate with a monitoring protocol for CMV viremia in patients receiving prophylaxis and treatment [ 71 , 72 ]. This type of antiviral stewardship approach may be an area of further exploration toward preventing CMV resistance in the post-HSCT population.…”

The next frontier: cytomegalovirus antiviral stewardship programs in solid organ transplant

“…The most complete description of a CMV ASP was published in 2022 [29 ▪▪ ]. This program targeting abdominal transplant recipients outlined a comprehensive approach, targeting prophylaxis in high-risk patients (donor seropositive, recipient seronegative), preemptive monitoring and treatment of CMV disease with subsequent secondary prophylaxis in patients at increased risk of recurrence [29 ▪▪ ]. The authors reviewed their longitudinal experience with creation and streamlining of the program based on center-specific quality improvement initiatives.…”

Maribavir for the Management of Cytomegalovirus in Adult Transplant Recipients: A Review of the Literature and Practical Considerations

“…Maribavir is an attractive option for PET in the PEM prophylaxis approach given tolerance and lack of myelosuppressive adverse effects, theoretically improving the likelihood of development of cell-mediated immunity (CMI) in the setting of replication priming events. 38,39 Additional larger scale phase 3 studies are needed to more clearly evaluate the long-term efficacy and development of resistance in this setting, specifically with multiple courses of PET, given the low genetic barrier to resistance associated with maribavir.…”