Therapeutic Myths in Solid Organ Transplantation Infectious Diseases.

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic "myths" may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population.

Reduced dosing versus full dosing valganciclovir for prophylaxis of cytomegalovirus in high-risk abdominal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a common infection in abdominal transplant recipients (ATR). Prevention of CMV in the highest risk population (CMV IgG donor+/recipient-) is critical as CMV is associated with negative outcomes. Guideline recommended prophylactic valganciclovir dosing is 900 mg daily for 6 months in this population. However, reduced dosing strategies are utilized in practice. METHODS: This single center, retrospective study in adult ATR compared full valganciclovir prophylactic dosing (900 mg daily for 6 months) to reduced dosing (900 mg daily for 3 months, then 450 mg daily for 3 months). The primary endpoint was incidence of CMV infection with viral load >1000 IU/mL. Secondary endpoints included incidence of CMV infection with viral load 200-1000 IU/mL, neutropenia, and leukopenia. RESULTS: Incidence of CMV infection with viral load >1000 IU/mL (29% vs. 27%, p = 1) or CMV infection with viral load 200-1000 IU/mL (6% vs. 12%, p = .421) did not differ significantly between 68 ATR in reduced and full dosing groups, as well as incidence of leukopenia (94% vs. 97%, p = 1) and neutropenia (77% vs. 70%, p = .586). CONCLUSIONS: There was no difference in the incidence of CMV infection, neutropenia, or leukopenia of the two dosing regimens, although time to CMV diagnosis was different.

Hydralazine-Induced Fulminant Liver Failure Requiring Urgent Liver Transplant: Common Drug With Rare Complication.

Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.

Evaluating Potentially Inappropriate Medications in Older Kidney Transplant Recipients.

OBJECTIVES: Beers Criteria and the Screening Tool of Older Persons' Prescriptions (STOPP) Criteria/Screening Tool to Alert to Right Treatment Criteria are used to assess potentially inappropriate prescribing and medications, which could pose a harm to those of older age. The purpose of this study was to assess and compare the use of Beers and STOPP Criteria in older kidney transplant recipients. METHODS: This was a dual-center, retrospective chart review from May 1, 2014, to March 1, 2018, including kidney transplant recipients 65 years and older. Those who underwent a dual transplant or had incomplete medical records were excluded. Outcomes included number of potentially inappropriate medications (PIMs) comparing Beers and STOPP Criteria on transplant admission, number of PIMs on admission compared with discharge, and readmissions within 3 months related to these medications. RESULTS: A total of 121 recipients were evaluated. On admission, 60 medications were listed on the STOPP Criteria compared with 106 medications on the Beers Criteria. When comparing PIMs on admission to discharge, there was a 38% decrease in the number of medications on discharge using the STOPP Criteria, whereas there was a 9% increase using the Beers Criteria. CONCLUSIONS: Older recipients were more likely to be on a medication listed in the Beers Criteria on admission and have a new medication listed in the Beers Criteria upon discharge compared with the STOPP Criteria.

Pharmacological management of patients undergoing total pancreatectomy with auto-islet transplantation.

Chronic pancreatitis results in permanent parenchymal destruction of the pancreas gland leading to anatomical and physiological consequences for patients. Surgical management varies, and some patients require total pancreatectomy with autologous islet cell transplantation (TPIAT). Patients undergoing TPIAT require complex and diligent management after surgery. This encompasses the management of glucose control (endocrine function of the pancreas) and supplementing loss of exocrine function of the pancreas with digestive enzymes. Other areas of management include optimizing pain relief while reducing narcotic usage, providing antimicrobial prophylaxis, and reducing loss of islet cells by improving its integrity through anticoagulation and use of anti-inflammatory agents. Each aspect of care is unique to this population. However, comprehensive reviews on its pharmacological management are scarce. This review will discuss the available literature to date surrounding all aspects of pharmacological management of patients undergoing TPIAT.

Methylprednisolone-Induced Hypersensitivity Reaction in a Liver Transplant Recipient.

Corticosteroids have an essential role as an immunosuppressive agent in transplant; because of their anti-inflammatory properties, they rarely cause an allergic reaction. Here, we report a liver transplant recipient who developed an allergic reaction to intravenous methylprednisolone sodium succinate. The deceased-donor orthotopic liver transplant recipient received intravenous methylprednisolone sodium succinate for induction during transplant, which was followed by another intravenous dose and oral prednisone taper. She was later treated with intravenous methylprednisolone sodium succinate taper for acute cellular rejection, which had been confirmed with a second biopsy. After admission for further treatment, she received another 1 g of intravenous methylprednisolone sodium succinate dose. About 15 to 20 minutes after receiving this dose, she presented with a new-onset urticarial rash that started on the trunk and progressed with facial edema. She continued a course of intravenous and oral dexamethasone for treatment of rejection and later was restarted on and tolerated oral prednisone. This case highlights the importance and the possibility of using dexamethasone as an alternative treatment approach for those with similar reactions to intravenous methylprednisolone sodium succinate.

Alemtuzumab in Renal Retransplantation - Transplant Outcomes and Associated Infections.

Renal retransplant patients have decreased graft survival compared with primary renal transplant patients. Alemtuzumab induction is often used at the time of retransplant; however, the literature surrounding alemtuzumab induction in renal retransplant patients is limited. In this single-center, retrospective, observational study, we aimed to determine the 1-year incidence of infections and transplant outcomes in renal retransplant patients who received alemtuzumab induction. Thirty-four patients who received alemtuzumab met inclusion criteria and were included in the final analysis. Twenty-two (64.7%) of these patients acquired infections. Of these, 7 patients (31.8%) acquired infections that resulted in hospitalization or intravenous antibiotics. The most common infections were urinary tract infections (n = 10; 29.4%), cytomegalovirus DNAemia (n = 7; 20.6%), and BK virus (n = 6; 17.6%). The use of steroid maintenance therapy after alemtuzumab induction did not increase the number of infections compared with patients with a steroid-free interval after alemtuzumab induction. The number of patients who developed de novo donor-specific antibodies (DSA) was 11 (32.4%) with only 1 of these patients having DSA before retransplantation. The incidence of acute cellular rejection was 2.9% (n = 1). There was no graft loss, and patient survival was 97% (n = 33). There were no significant differences in infection rate or DSA development between alemtuzumab and the other induction agents, antithymocyte globulin and basiliximab, among retransplanted patients. Alemtuzumab induction in renal retransplant patients resulted in similar bacterial and viral infection rates as previously reported in the literature and did not negatively impact graft and patient survival.

Potential to Mitigate Disparities in Access to Kidney Transplant in the Hispanic/Latino Population With a Specialized Clinic: Single Center Study Representing Single State Data.

BACKGROUND: We sought to evaluate potential disparities in kidney transplant rates in a single state in the United States. We studied the potential to mitigate disparities with a specialized clinic using it as a model presentation. METHODS: Based on data from the United States Renal Data System and Organ Procurement and Transplantation Network, we estimated the yearly end-stage renal disease and waitlist addition, stratified by race/ethnicity from 2000 to 2018. Institution rates were analyzed similarly, and the implementation of a focused Latino clinic was evaluated. RESULTS: The number of patients added to the national transplant waitlist has increased by 40% in non-Latino whites and by 160% in Latinos from 2000 to 2017. Comparing the period from 2000 to 2004 to 2015 to 2018 in North Carolina, the waitlist increased for Latino patients by 482% and non-Latino whites by 23%. One year after a designated Latino transplant clinic at our institution, there was a 125% increase in the number of Latino referrals for kidney transplant evaluation, a 142% increase in the number of waitlisted Latino patients, and an increase in kidney transplants of 145%. CONCLUSION: With the increasing number of patients in the Latino community who are diagnosed with end-stage renal disease, there is a direct benefit for a culturally competent program that addresses access to transplants.

Utilizing multimodal analgesia to evaluate postoperative analgesic requirements in kidney transplant recipients.

The use of non-opioid analgesics following surgery has proven beneficial in managing pain and decreasing adverse outcomes following surgery. Data assessing outcomes related to opioid use is limited in kidney transplant recipients (KTRs). We evaluated the effectiveness of implementing a reduced to no opioid use protocol in KTRs. This retrospective cohort study included adult KTRs between January 2017 and July 2019 with a multimodal analgesic protocol (MAP), focused on limiting opioids, implemented in August 2018. We compared analgesic requirements in morphine milligram equivalents (MME) during transplant admissions between the MAP cohort and traditional cohort. There were 217 KTRs who met the criteria. Inpatient opioid use was significantly reduced in the MAP cohort (16.5 ± 19.2 MME/day vs 24.7 ± 19.7 MME/day; P <.05) with no significant difference in pain scores. No use of opioids within six months of discharge was significantly increased in the MAP cohort (50% vs 7%; P <.001), and there were no reported deaths at six months in either cohort. The use of multimodal analgesia is beneficial in KTRs to provide adequate pain control with limited to no exposure of opioids during admission or at discharge.

Early Use of Tacrolimus Extended-Release in a Pediatric Kidney Transplant Recipient.

Tacrolimus extended-release pharmacokinetics and its once-daily formulation provide beneficial properties, and its use has been evaluated in the adult kidney transplant population. Here, we report a case of successful conversion from tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a pediatric kidney transplant recipient.

The Effect of Tacrolimus Trough Variability on Kidney Transplant Outcomes.

PURPOSE: Variability in tacrolimus levels has been associated with increased rejection, graft loss, and de novo donor-specific antibody (dnDSA) development in kidney transplant recipients (KTRs); however, limited data on alemtuzumab induction or infection exist. We sought to determine the impact of tacrolimus variability in KTRs on dnDSAs, graft outcomes, and infections 3 years posttransplant after alemtuzumab induction. METHODS: Adult KTRs from January 1, 2013, to December 31, 2017, receiving alemtuzumab and tacrolimus-based immunosuppression at a single center were included. Tacrolimus variability was calculated using coefficient of variability (CV), and high CV was defined as ≥30%. Graft and infectious outcomes were assessed between high and low CV groups. RESULTS: Two hundred fourteen KTRs were included. The median tacrolimus CV from 0 to 3 months and from 3 to 12 months was 28.1% and 25.8%, respectively. Recipients with high CV had decreased glomerular filtration rate at 3 and 12 months (67.7 ± 35.48 vs 80.7 ± 29.3, P = .01 and 70.9 ± 35.4 vs 83.3 ± 30.2, P = .015). High CV was also associated with increased cytomegalovirus viremia and disease (19.6% vs 9.3%, P = .046 and 6.4% vs 17.9%, P = .015). No difference in biopsy-proven acute rejection, survival, or dnDSA development at 3 years was observed. CONCLUSIONS: High tacrolimus variability was associated with significantly reduced graft function and increased cytomegalovirus viremia and disease but not biopsy-proven acute rejection, survival, or dnDSA development.

Use of anti-inflammatory agents in clinical islet cell transplants: A qualitative systematic analysis.

Immunologic and non-immunologic loss of islet cells upon their transplantation into the liver leads to suboptimal outcomes. Anti-inflammatory agents are used during autologous and allogeneic transplantation. The aim of this qualitative systematic literature review is to evaluate their clinical use and safety. Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, ClinicalTrials.gov, and EU Clinical Trials Register were searched. Of the 216 unique citations, 10 with tumor necrosis factor (TNF) blockers [etanercept (ETA) or infliximab] and 3 with both TNF blockers and an interluekin-1 receptor antagonist [anakinra (ANA)]) were included. Of these, 12 were in allogeneic and one in autologous transplant. Insulin independence with decreased islet cells and number of transfusions were reported with their use. One infection was reported in a group receiving ETA. Analysis suggested that the use of ETA ± ANA have the potential to improve outcomes in islet cell transplant.