This concerning trend of escalating inpatient days, costs, and increased morbidity and mortality is expected to persist as our annual transplant volume continues to grow. As of December 2024, UCSF ranks as the second all-time highest volume transplant center in the United States, having performed a total of 18,449 organ transplants, according to the Organ Procurement and Transplantation Network (OPTN). 

TARGET Published literature supports that pharmacist-led CMV stewardship initiatives can reduce CMV infection rates, CMV-related hospital admissions, and CMV resistance rates by over 40%.1-3 Furthermore, when patients develop (val)ganciclovir resistance, literature suggests that there is a ten-fold increase in associated total hospital costs ($200,000 vs $20,000).4 Based on published literature and success of these pharmacist-led initiatives, our goal is to implement a pharmacist-run CMV stewardship program aimed at reducing CMV-related hospital admissions, inpatient days, associated costs, and the development of CMV resistance by 25%. This would result in a reduction of annual CMV-related hospital admissions from 30 to 22 and a decrease in inpatient days from 438 to 328. With an estimated direct variable cost of $1,688 per bed for the 2023-2024 academic year, we anticipatecost savings of at least $183,992 (excluding ICU bed costs) from a 25% reduction in patient days. 

In 2024, the total cost associated with CMV infection admissions was $2,470,406. We project a 25% reduction in costs, resulting in total savings of $617,601. Lastly, we anticipate a 25% reduction in the development of CMV resistance. In 2024, 33 CMV genotyping tests were ordered at a cost of $1,945 per test. With a 25% reduction in resistance and the subsequent need for fewer genotyping tests, we expect to save $16,000.  

We utilized Slicer Dicer within Apex to determine the number of admissions, total length of stay, and total associated costs for CMV infection as the principal problem for admission. 

GAPS Currently, there is significant variability in CMV management within the lung transplant program at UCSF, as well as across other organ transplant groups. In the existing workflow, CMV viral load results are reviewed alongside renal function during daily lab review (Monday through Friday) with nurse coordinators and an APP, fellow, or attending. Due to the high volume of labs reviewed, there is often insufficient time to individualize and comprehensively assess each CMV result and corresponding change in renal function. Additional challenges include the absence of updated, standardized protocols regarding when to initiate treatment dosing of valganciclovir versus when to continue monitoring, resulting in confusion and inconsistent practices.  

Within Apex, there has been the use of different creatinine clearance calculators that may utilize an inappropriate patient weight leading to under or over estimating creatinine clearance, further complicating dosing decisions. Additionally, if a patient has not had a weight or serum creatine in the past twenty-one days, Apex will not calculate a creatinine clearance, leading providers to potentially calculate it incorrectly. Moreover, there has been an overuse of CMV genotyping in patients without clinical suspicion of resistant or refractory disease, or without sufficient viral load for the test to be run, leading to unnecessary costs and increased patient burden due to the need to travel long distances to UCSF for testing. 

Many patients routinely have laboratory tests conducted at non-UCSF facilities, requiring manual entry of results into the Apex system.This process introduces equity gaps, resulting in delays in receiving test results, adjusting valganciclovir dosing, and initiating timely treatment for breakthrough CMV infections.These delays contribute to the emergence of resistant CMV strains, which may ultimately necessitate inpatient treatment with intravenous foscarnet or maribavir. Patients who are most adversely affected are those residing in remote communities with limited access to local laboratory services.  

INTERVENTION  We propose the implementation of a pharmacist-led CMV stewardship initiative, modeled after successful programs at other institutions, which have demonstrated reductions in the incidence of CMV viremia and breakthrough infection, faster time to CMV eradication, lower rates of CMV resistance, and a decrease in CMV-related hospital admissions.1-3  Furthermore, these stewardship models have facilitated a shift in patient-centered care from reactive to proactive, leading to improved patient outcomes and a reduction in the duration of valganciclovir therapy needed to achieve viral clearance, which can help reduce risk of myelosuppression in an already vulnerable population.1 

This pharmacist led initiative will be implemented in the outpatient setting and integrated into the workflow of the covering outpatient pharmacist for each respective organ group.First, an updated UCSF CMV protocol will be developed in collaboration with Infectious Disease Specialists, Lung Transplant Specialists, and Transplant Pharmacists to align with current practices and streamline CMV management. To ensure the sustainability and long-term success of the initiative, we will initially focus on the highest-risk populations, including CMV mismatch patients (donor CMV IgG positive, recipient CMV IgG negative), individuals with an active CMV viral load, and those receiving alternative therapies for CMV (such asletermovir,maribavir, foscarnet, or cidofovir). 

Working with Phoenix and informatics teams, an Episode of Care Encounter will be created to facilitate the enrollment and monitoring of these high-risk patients. A daily report (Monday through Friday) will be generated within Apex, enabling the covering clinic pharmacist to review enrolled patients. The pharmacist will clinically assess the patients' new lab results and may take one of the following actions, as clinically appropriate: adjust the dose of valganciclovir, modify the frequency of CMV viral load monitoring, or order CMV resistance genotyping. Additionally, the pharmacist will communicate with the covering attending physician and make recommendations regarding changes to immunosuppression, admission for intravenous therapies in cases of suspected refractory or resistant CMV, or switching to alternative therapies due to adverse effects. 

Through the Episode of Care, the pharmacist will be able to document a concise, standardized note utilizing DOT phrases, which will be routed to the nurse coordinator and sent to the patient via MyChart. The nurse coordinator will then follow up with the patient to ensure the necessary changes are implemented. Communication of medication changes with patients by the nurse coordinator is already a standard of practice within our workflows. The pharmacist will also assign a follow-up date to the encounter, and the daily report will allow sorting based on the next follow-up date, enabling timely review of labs and ensuring that the pharmacist can reach out if labs are not completed as expected. 

All high-risk CMV patients will be enrolled in the CMV initiative during their index hospitalization for transplantation by the covering inpatient transplant pharmacist. In the outpatient setting, when an CMV VL is detected, an alert will be triggered in Apex and sent to the respective pharmacist’s pooled in-basket. The pharmacist will then enroll the patient for ongoing management. Additionally, patients currently receiving alternative therapies will be enrolled for monitoring of CMV VL to detect any breakthrough viremia, or at the time of transitioning to alternative therapies. 

Potential barriers to implementation include ongoing challenges in obtaining lab results promptly for patients in remote areas whose EHRs do not integrate with ours, as well as difficulties in obtaining CMV resistance genotyping at outside hospitals or labs. Additional challenges include medication non-compliance leading to breakthrough CMV infection and insurance authorization for alternative therapies such as maribavir or letermovir. While we anticipate staffing coverage of this initiative to assimilate into our current workflow, there is a potential barrier for staffing gaps if a pharmacist(s) is on vacation and may require the inpatient pharmacist to review the daily report.

PROPOSED EHR MODIFICATIONS We need to develop a new workflow for CMV monitoring for transplant recipients at UCSF within Apex utilizing Episodes of Care Encounters. This platform will facilitatetimely, reliable, and closed-loop communication among multiple stakeholders—patients, transplant pharmacists, and nurse transplant coordinators—from laboratory result review to patient instructions. Please see the attached document outlining specific EHR modifications.