Votruba, Cassandra

Abstract Objective: To define the incidence of donor-derived infection (DDI) in recipients of solid organ transplant (SOT) from donors with positive blood cultures and to assess the impact of shorter versus longer duration of targeted preemptive antibiotic therapy (PAT). Design: Retrospective, single-center, cohort study. Setting: Mayo Clinic Arizona. Patients: Recipients transplanted between 1/1/2019 and 7/1/2024 who received an organ from a donor with positive blood cultures. Methods: The primary outcome was incidence of DDI. Secondary outcomes included duration of PAT and incidence of donor blood culture contamination. Results: Among 199 SOT recipients from 167 unique donors with positive blood cultures, two recipients developed confirmed DDI within 30 days of SOT. Both cases were gram negative bacillary bacteremia not treated in donors and occurred immediately posttransplant prior to adequate recipient PAT. Six-month graft survival and recipient survival were 96.5% and 97.5% respectively. 139 recipients (69.8%) received PAT for a median duration of 7 days. There was no difference in rate of infections between recipients provided with ≤7 days versus 8–14 days of PAT for donor blood cultures; however, recipients who received 8–14 days had more Clostridioides difficile infections (CDIs) within 60 days of SOT (7.7% vs 1.5% ≤ 7 days, P = .040) and were more often discharged on intravenous antibiotics (32.3% vs 11.3%, P < .001). Conclusion: We observed a low rate of DDI following receipt of organs from donors with positive blood cultures. DDI occurred in cases without adequate donor/recipient treatment. Longer durations of targeted PAT resulted in more CDI and intravenous antibiotics on discharge.

ABSTRACT Trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis can prevent Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections (OI). We sought to assess the frequency, causative factors, and impact of early TMP/SMX discontinuation in abdominal solid organ transplant (SOT). This is a single‐center, retrospective cohort study of abdominal SOT recipients at Mayo Clinic Arizona (MCA) between January 2021 and June 2023. Primary study goals were to determine the rate and reasons behind early TMP/SMX discontinuation and whether TMP/SMX prophylaxis was reinitiated. Secondary outcomes included mean duration of therapy, alternative prophylactic agent utilized, and incidence of TMP/SMX‐preventable OI. A total of 930 abdominal SOT recipients were included (592 kidney, 253 liver, 85 multiorgan transplants). TMP/SMX was discontinued early in 184 (20%) patients: 77 kidney, 84 liver, 23 multiorgan. Predominant reasons for discontinuation were hyperkalemia (39%) and cytopenias (35%). Median duration of TMP/SMX prophylaxis before discontinuation was 54.5 (18.0, 93.2) days. TMP/SMX was not resumed in 62% of cases (36% kidney, 89% liver, 52% multi‐organ). The predominant reason for non‐resumption was alternative prophylaxis with no clear intent to rechallenge TMP/SMX (70%). Alternative prophylaxis included pentamidine (43%), none (30%), dapsone (22%), and atovaquone (5%). Of patients reinitiated, 86% (59/69) successfully remained on TMP/SMX through the prophylaxis period. One TMP‐SMX‐preventable OI (nocardiosis) was observed in the TMP/SMX discontinuation group. TMP/SMX is often discontinued prematurely in SOT recipients without resumption despite resolution of the offending cause. TMP/SMX prophylaxis should be maintained where possible, as alternative therapy may not offer the same broad spectrum of protection against OI.

Abstract Background Trimethoprim-sulfamethoxazole (TS) prophylaxis can prevent Pneumocystis jirovecii (PCP) and other opportunistic infections (OIs), such as intestinal protozoa, Toxoplasma, Listeria, and Nocardia. We sought to assess the frequency, causative factors, and impact of early TS discontinuation in abdominal SOT recipients. Methods This is a single-center, retrospective cohort study of adult abdominal SOT recipients at Mayo Clinic Arizona between 1/1/2021 and 6/30/2023. Objectives included the rate and reasons behind early TS discontinuation and whether TS prophylaxis was reinitiated. Early discontinuation was defined as cessation of TS prophylaxis within 6 months post-transplant for ≥7 days. Secondary outcomes included median duration of therapy, alternative prophylactic agent utilized, and incidence of TS preventable OI. Patients were excluded if they had no TS ordered, died &lt;180 days from transplant, or received a thoracic organ transplant. Results 942 abdominal SOT recipients were identified. Thus far 171 liver, 11 Kidney, and 29 liver/kidney have been reviewed and included in the current analysis. TS was discontinued early in 60 (28%) patients. Predominant reasons for discontinuation were hyperkalemia (45%), cytopenias (17%), and acute kidney injury (15%). Allergy was the indication for discontinuation in 1 patient. Median duration of TS before discontinuation was 39 days (IQR 66). TS was not resumed in 78% of cases. The predominant reason for non-resumption was alternative prophylaxis with no clear intent to rechallenge TS (70%). The main discontinuation reason had resolved in 70% that stopped due to cytopenias, 67% that stopped due to liver injury, and 96% that stopped due to hyperkalemia. Alternative prophylaxis included pentamidine (50%), dapsone (32%), atovaquone (5%), none (13%). No patients developed PCP or other TS preventable OI during 9-month follow-up post-SOT. Conclusion TS is discontinued prematurely in a significant number of SOT recipients and is often not resumed despite resolution of the offending cause. Given its proven track record in preventing several OIs in SOT recipients, providers should document reason(s) for TS discontinuation and consider resumption of TS after reasons for discontinuation resolve. Disclosures All Authors: No reported disclosures

AbstractTixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre‐exposure prophylaxis against COVID‐19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID‐19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID‐19 infection, severity of COVID‐19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty‐seven (6.5%) patients tested positive for COVID‐19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID‐19 by type of organ transplant (p = .122). Twenty‐five of the 27 patients testing positive for COVID‐19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID‐19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID‐19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.