Citations

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to facilitate temporary tacrolimus cessation in the setting of acute kidney injury (AKI). Objective: The primary objective of this study was to describe renal recovery after temporary tacrolimus cessation with non-induction basiliximab (NIB) compared to a matched cohort. Methods: We conducted a single-center study of adult cardiothoracic transplant recipients that received basiliximab beyond post-operative day 7 for temporary tacrolimus cessation in the setting of AKI between January 2019 and November 2023 and matched them to acontrol cohort. Results: Twelve patients underwent temporary tacrolimus cessation with NIB. In total, 7 (58%) patients achieved initial renal recovery at tacrolimus resumption compared to 15 (42%) patients in the matched cohort at an equivalent time point. No difference between treated rejection (17% vs. 19%, p = 0.80) or infection (75% vs. 50%, p = 0.32) was observed between tacrolimus cessation and its matched cohort. Conclusions: The use of NIB for tacrolimus cessation can allow for potential renal recovery after an AKI or in patients at risk of AKI. This approach does not appear to significantly increase the risk of rejection but may increase the risk of infection in the long term.

ABSTRACT Background Risk for medication error increases during care transitions. Error susceptibility increases in pediatrics due to age and weight‐based dosing. Governing bodies acknowledge errors endanger patients, and transplant pharmacotherapy experts are mandated by the Center for Medicare and Medicaid Services (CMS). Pharmacist‐led medication histories reduce errors; however, pharmacists' roles in the transitions of care between transplant centers are unaddressed by CMS. We assessed the impact of transplant pharmacist involvement in medication histories for pediatrics transitioning between transplant centers. Methods Pediatric patients pre‐ or post‐heart transplant transitioning to our center were proactively identified. Transplant pharmacists conducted medication histories by phone with caregivers and tracked discrepancies between existing medication lists and interview responses. Descriptive statistical analyses were completed. Results Of 27 patients identified, seven caregivers were uncontactable, one declined participation, and 19 underwent transplant pharmacist medication history. Medication list errors were detected in 100% of patients ( n = 19), with a median [IQR] of 5 [3–11] issues per patient. Of 122 issues, 72 (59%) were inaccurate or missing data, 17.2% ( n = 21) listed stopped drugs, 9.8% ( n = 12) revealed incorrect administration routes, 7.4% ( n = 9) were duplicate medications, and 6.6% ( n = 8) of errors were medications needing to be added. Corrections included updating 84 inaccuracies (68.8%); removing/adding drugs (30 [24.6%] and 8 [6.6%], respectively); and team communication. Conclusions Complex dosing strategies in pediatrics confer error vulnerability. Designing transition of care processes with transplant pharmacist involvement in medication histories can assist in ensuring medication list accuracy, thereby improving pediatric patient safety.

ABSTRACTItraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34–230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95–195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93–174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced‐dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.

AbstractBackgroundTransgender and gender‐diverse (TGD) patients experience challenges and disparities when seeking health care across a multitude of settings. Studies have demonstrated that TGD individuals experience bias when interacting with health care providers, including pharmacists in the community and hospital settings. Without proper training, pharmacists are less likely to be prepared to provide equitable and optimal patient care to TGD patients. This quality improvement initiative aimed to identify gaps in pharmacist knowledge and comfort with regard to TGD health care.MethodsA 29‐item reflective questionnaire was designed to collect information on pharmacist training and experiences in caring for TGD patients. The survey was distributed via email to all 490 pharmacists within a single health system and responses were collected from October 23, 2023 to November 3, 2023.ResultsA total of 116 pharmacists completed the survey, for a response rate of 24%. Although 77% of respondents reported caring for a TGD patient, only 21% reported receiving any formal education or training on TGD health care. While 83% of respondents agreed that formal education on TGD health care is important, and 90% indicated that education on gender‐affirming therapy is important, a majority of pharmacists disagreed that they were comfortable with making recommendations and providing counseling on gender‐affirming therapy. A majority of pharmacists were interested in formal education and engaging in departmental initiatives to improve TGD care.ConclusionsThere was a gap in confidence and education in caring for TGD patients among pharmacists practicing in a single academic institution. Pharmacists reported that more education is warranted to bridge current gaps in pharmacist comfort and TGD health care.

Background. Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods. We performed a retrospective cohort study of PT recipients from 2010–2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results. Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions. Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

AbstractSolid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events due to comorbidity burden and the complexity of their medication regimens. Urgent management of post‐transplant complications often falls to the generalist clinician or critical care specialist. The purpose of this narrative review is to discuss innovations and bedside applications of pharmacogenomics and therapeutic drug monitoring applied to immunosuppression and agents frequently encountered in transplant recipients. Medication formulations will be given specific attention, as interchange is frequently required in the acute care setting. Bioassays quantifying immune system activity will be described with practical applications. A structured approach to addressing drug–drug, drug‐gene, and drug–drug‐gene interactions will be modeled using a case‐based approach synthesizing pharmacogenomics, therapeutic drug monitoring, pharmacokinetics, and pharmacodynamic principles.