Vikram, Holenarasipur R.

Abstract Background Strongyloides stercoralis is an intestinal parasitic nematode with a 2% - 7% prevalence in the United States. Immunosuppression can predispose to disseminated infection, concurrent bacterial sepsis and significant morbidity and mortality. We sought to review positive Strongyloides serology (PSS) results across 3 academic medical centers. Methods Electronic medical records of patients with PSS were reviewed between 2012 and 2023. Extracted data included demographics, country of origin, travel history, testing indication, clinical presentation, treatment regimen and duration. Patients were classified into chronic infection (PSS without additional clinical manifestations), hyper infection syndrome (cutaneous, gastrointestinal tract, or lung involvement), and disseminated infection (evidence of involvement of distant sites beyond hyper infection such as the brain, liver, kidneys, or bloodstream). Results Overall PSS rate across the 3 sites was 5.5%. A total of 412 patients with PSS were identified with a mean age of 56.7 years (SD ±14.2); 272 (66%) were male. The primary indication for testing was transplant evaluation in 230 (56%), eosinophilia workup in 84 (20%), suspicion of active infection in 74 (18%), travel history in 27 (7%), and pre-immunosuppression screening in 27 (7%). 401 (97.3%) were categorized as chronic infection,10 (2%) as hyper infection, and one patient (0.2%) as disseminated infection. Treatment was administered to 366 (89.3%) patients: 226 (61.7%) received 2 doses of Ivermectin on consecutive days, 94 (25.7%) received a single dose, 26 (7.1%) received 2 doses repeated 2 weeks later, and 20 (5.5%) received alternative regimens. The patient with disseminated infection received 2 weeks of Ivermectin followed by monthly dosing. Conclusion Majority of the patients with PSS were asymptomatic, and treatment regimens were not uniform. Screening should be considered for patients currently receiving or initiating long-term immunosuppression that can potentiate Strongyloides dissemination. Developing a targeted testing algorithm based on epidemiologic factors, clinical suspicion, laboratory parameters and nature of immunosuppression can help identify at-risk patients who can receive pre-emptive therapy if infected. Disclosures All Authors: No reported disclosures

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was –1.5, corresponding to a predicted survival of 33–57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.

Pneumocystis pneumonia (PCP) is a serious fungal infection affecting immunocompromised hosts. Decompensated cirrhosis leads to cirrhosis-associated immune dysfunction (CAID), a form of impaired cellular immunity that may predispose patients to opportunistic infections such as PCP. We conducted a retrospective review of 727 patients with proven or probable PCP from 2017 to 2025. Of these, 33 had decompensated cirrhosis. These patients were stratified into two groups: Cirrhosis Only (n = 16) and Cirrhosis with Additional Immunocompromising Conditions (n = 17). Among the patients with cirrhosis, the overall mortality was 48%, with the 90-day mortality reaching 57.6% (95% CI: 39.2–74.5%). Compared with those without cirrhosis, the patients with cirrhosis had a higher risk of mortality (OR: 4.08, 95% CI: 2.01–8.30, p < 0.001), increased intensive care unit (ICU) admission (87% vs. 42%, p < 0.001), and greater need for renal replacement therapy (54.6% vs. 7.5%, p < 0.001). These findings suggest that decompensated cirrhosis alone may represent a sufficient and underrecognized risk factor for PCP, with a high associated mortality. Given the preventable nature of this infection, future studies are needed to assess the incidence, define the risk, and investigate the role of prophylaxis in this vulnerable population.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is increasingly seen in patients who are non-HIV immunocompromised hosts, yet modern risk factors and outcomes are poorly recognized and defined. Methods A retrospective review was conducted of adult patients who met criteria for proven or probable PCP from 2017 to 2024 across a large academic multicenter health system. The primary outcome was mortality among cohorts, defined by etiology of immunosuppression through univariate and age-adjusted logistic regression. Secondary analyses included trends in annual diagnoses and testing patterns. Results A total of 701 patients met criteria for inclusion, representing one of the largest clinically characterized cohorts of PCP to date. The median age was 65 years (IQR, 54–73) and 62% were male. The most common risk groups were hematologic malignancy (32.2%), solid tumor cancers receiving chemotherapy (22.4%), and autoimmune disease with immunosuppression (17.7%). Annual PCP diagnoses increased at a rate of 15.8% (95% CI, 8.9%–23.2%) in parallel with increased testing. Only 5.4% of patients were receiving prophylaxis at the time of diagnosis. Overall mortality was 20% (95% CI, 17%–23%) and highest in cirrhosis (adjusted odds ratio, 6.24; 95% CI, 2.84–13.69; P &lt; .001). Conclusions PCP in the current era affects a broad range of patients who are immunocompromised, with high associated mortality and low rates of prophylaxis. Patients with solid tumors and those with cirrhosis are at particularly high risk of mortality. These findings highlight the need to reassess and redefine PCP prophylaxis guidelines in specific populations and our understanding of who is at risk.

Abstract Donor-derived tuberculosis is a rare complication following solid organ transplantation, and tuberculosis screening is not a current transplant prerequisite for most donors. Donor-derived tuberculosis usually presents sooner than reactivation tuberculosis, and the most common finding is fever. We present 3 cases of donor-derived tuberculosis in the recipients of 2 kidneys and 1 liver from the same donor, who presented with unexplained fevers occurring 4–5 weeks after transplantation. Initial antibacterial therapy failed in all 3 patients, leading to further testing, which identified Mycobacterium tuberculosis by culture and molecular studies. All recipients successfully received tuberculosis therapy but had significant morbidity and prolonged hospital stays. Donor-derived tuberculosis should be among the differential diagnoses of unexplained fever in solid organ transplant recipients in the first few months after transplantation. Screening protocols should be implemented for donors with an epidemiologic risk of tuberculosis, with special emphasis on deceased donors.

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.

ABSTRACTIntroductionVaccination is crucial to the thoracic solid organ transplant (SOT) population to reduce vaccine‐preventable infection. However, data on posttransplant hepatitis B virus (HBV) vaccination compliance and vaccine‐induced seroprotection are lacking.MethodsWe conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Recombivax HB was used before 2020, and Heplisav‐B was preferred after 2020. Recipients with posttransplant hepatitis B surface antibody (HBsAb) < 10 IU/L were eligible for the HBV vaccine. HBV seroprotection was defined as an HBsAb ≥ 10 IU/L.ResultsA total of 1116 recipients were evaluated, all of whom underwent posttransplant HBsAb testing. Of these, 751 (67%) had an HBsAb level < 10 IU/L and were eligible for posttransplant HBV vaccination. Of the eligible recipients, 117 (16%) completed the HBV vaccine series during the study period. Among these 117 recipients, 40 (34%) had their HBsAb levels rechecked after completing the vaccine series, with a seroprotection rate of 37.5% (15/40). There was no statistically significant difference in the seroprotection rates between Heplisav‐B and Recombivax HB vaccines (39% [13/33] vs. 29% [2/7]; p = 0.691). In addition, HBsAb levels were lowest at week 2 but rebounded at week 4 posttransplant and pretransplant HBsAb levels of ≥100 IU/L ensured 5‐year seroprotection.ConclusionSuboptimal compliance with HBV vaccination and poor vaccine‐induced seroprotection occur in thoracic organ transplant recipients, regardless of the vaccine used. These findings underscore the necessity of enhancing vaccination strategies for SOT recipients. image

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