Vikram, Holenarasipur R.

Abstract Background Mycobacteirum Szulgai is a non-tuberculous mycobacterium known to cause human disease. Descriptions in the literature are limited to case reports and a larger case series from the Netherlands. Guidelines from the American Thoracic Society recommend that M. szulgai should always be considered pathogenic and that treatment should be based on in-vitro susceptibilities. Demographics and patient characteristics Methods We embarked on a retrospective study of adults ( >18 years) with M. szulgai infection at the Mayo Clinic sites in Arizona, Minnesota, and Florida. We queried the Mayo Clinic Database using two different search methods, (Advanced Text Explorer and the Mayo Data Explorer) using the terms ‘Mycobacterium Szulgai,’ ‘Mycobacteria Szulgai’,’ M. Szulgai’ and ‘Szulgai.’ Medical records from 1994 to 2023 were reviewed. Diagnostic studies Results Initial search yielded 43 patients. Twenty-seven patients were excluded (incomplete records or prior history of infection treated elsewhere). For our cohort of 16 patients, the mean age was 65 years [IRQ 57-74 years], 13 of those were caucasian. Five patients [31%] were immunosuppressed. Thirteen patients [81%] developed pulmonary infection, 5[31%] had extra pulmonary infection (2[12%] with disseminated disease and 3[19%] with extra-pulmonary disease without primary pulmonary infection). Only 8 [50%] patients received specific therapy. All treated patients met ATS criteria for NTM infections, while 3 [19%] untreated patient met criteria. Only 4 [25%] patient received therapy based on susceptibilities. The most common regimen was a combination of rifampin, ethambutol and macrolide in 5[31%] of the patients. Seven patients [47%] were cured, 4[27%] had ongoing symptoms, 1[7%] had relapse and 1 [7%] is currently receiving therapy. There were 2[ 13%] deaths in the untreated group and none from the treated group. One patient was lost to follow up. Treatment and outcomes Conclusion Our findings echo published literature and ATS recommendations that M. szulgai should be regarded as a true pathogen that necessitates targeted therapy. Disclosures All Authors: No reported disclosures

Abstract Background Recipients of solid organ transplant (SOT) have higher risk for infections, and the prevalence of mycobacterium tuberculosis liver abscess (MTB-LA) without pulmonary/disseminated MTB is 0.34%. However, there is little research on MTB-LA in SOT recipients. Mycobacterium tuberculosis Liver Abscess Cases Upon extensive literature review, this chart details all published, English-language cases of mycobacterium tuberculosis liver abscess in solid organ transplant recipients. Methods We conducted an extensive literature review of MTB-LA in adult SOT recipients. Results Our review showed 4 cases of MTB-LA in SOT recipients (table below). We detail 1 additional case. A 58-year-old male with ESRD due to type 2 diabetes mellitus, and latent MTB underwent kidney transplantation in March 2023. He completed a 6-month course of isoniazid and vitamin B6 for latent MTB 1 month before transplant. His post-operative course was uncomplicated; he was discharged to follow up with his nephrologist. He later developed norovirus illness with fever, which was conservatively managed. He developed new fevers 3 months post-transplant and CT of the abdomen/pelvis revealed a liver abscess, which was treated with empiric broad spectrum antibiotics, and was not amenable to aspiration. At his 4-month post-transplantation, he complained of fatigue, night sweats, poor appetite, and weight loss requiring hospitalization, wherein an MRI of the abdomen/pelvis identified a 3.6 x 3.2 x 6.2 cm liver abscess. The liver abscess aspirate was positive on acid fast bacilli smear and MTB polymerase chain reaction. He was initiated on antituberculosis therapy with isoniazid, rifabutin, pyrazinamide, and ethambutol. Susceptibilities identified pyrazinamide resistance, and led to substitution with levofloxacin. Labs, imaging and microbiology testing were negative for evidence of pulmonary/disseminated MTB. His donor’s information was reviewed; no obvious risk factors for active MTB were found. The recipient of the mate kidney is doing well without evidence of MTB infection. After 2 months of 4-drug antituberculosis therapy, ethambutol was discontinued. CT scan of the abdomen and pelvis at 4 months post anti-tuberculosus therapy revealed a 3 cm area of residual inflammation at the site of prior MTB-LA, in the setting of resolution of prior symptoms. Conclusion Early imaging and diagnostic aspiration of liver abscess with specific stains, culture and PCR testing can facilitate rapid diagnosis and initiation of antituberculosis therapy. Disclosures All Authors: No reported disclosures

Background. Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive. Methods. We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non–lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls). Results. No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results (P < 0.001). Conclusions. For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.

Abstract Background Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non–donor-derived LCMV infection in solid organ transplant recipients. Methods Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted. Results LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection. Conclusions Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.

ABSTRACTBackgroundAdenovirus (ADV) infection can lead to significant morbidity and mortality in immunocompromised patients, particularly in those with hematopoietic stem cells or solid organ transplants. The incidence of ADV infection in kidney transplant (KT) is not well‐defined as ADV is often asymptomatic and not routinely checked.MethodsThis retrospective case‐series study included KT and simultaneous pancreas‐KT (SPKT) recipients from January 1, 2008, to January 31, 2024, across three Mayo Clinic sites (Arizona, Florida, and Minnesota) with symptomatic adenovirus polymerase chain reaction cases. The primary outcomes were allograft function at various intervals post‐ADV infection, allograft, and patient survival.ResultsWe report one of the largest multi‐site case series regarding outcomes of ADV in KT with 17 patients. The median time to ADV infection was 30 weeks (5–74). Five patients (29%) developed disseminated infection. Nine patients (53%) of the entire cohort experienced graft loss within a median of 35 (4–168) weeks, with four (44%) of graft loss attributed to ADV. Nine patients (53%) developed rejections post‐ADV infection with a median of 4 (2–8) weeks after resolution. One patient died from acute hypoxic respiratory failure from ADV infection.ConclusionADV should be considered in KT/SPKT patients with renal dysfunction, hematuria, and with or without fever. Despite the low mortality rate, there is a significant risk of graft loss and rejection after ADV infection. It is crucial to screen for ADV and develop intervention strategies for treatment. Further multicenter studies are needed to better define, stage, and manage ADV infection. image

AbstractBackgroundDevelopment of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.MethodsThis is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.ResultsA total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%.ConclusionBrain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. image

ABSTRACT Introduction Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients. Methods We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30). Results Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001). Conclusions Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

Background. Identification and treatment of latent tuberculosis infection (LTBI) mitigate the risk of tuberculosis (TB) reactivation after transplantation. TB reactivation is higher in those with indeterminate QuantiFERON (QFT) than those with negative results. Management of indeterminate QFT results in the pretransplant period remains unclear. Methods. We conducted a retrospective study of solid organ transplant (SOT) recipients, 18 y and older, who were screened with QFT assay pretransplantation at Mayo Clinic between January 2010 and June 2023. We examined the frequency of indeterminate QFT results, results of repeat LTBI screening, treatment decisions, and rate of posttransplant TB infection. Results. Of 13 008 patients screened for LTBI before SOT, 736 (6%) patients had indeterminate QFT results. Among these, 247 (34%) underwent a second LTBI screening test, and 39 (5%) received LTBI treatment. Among 247 patients with a repeat LTBI screening test, 185 (75%), 48 (19%), and 14 (6%) were tested by QFT, T-SPOT.TB, or TST, respectively. The repeat QFT remained indeterminate in 160 (86%) patients, whereas all T-SPOT.TB results were negative. Posttransplant TB infection occurred in 2 (0.3%) patients; neither had a second TB screening test pretransplant nor received LTBI treatment. Conclusions. In SOT recipients with indeterminate QFT results at pretransplant evaluation, opting for T-SPOT.TB as a second test may be preferable over repeat QFT. TB infection after transplantation in patients with a pretransplant indeterminate QFT result was rare. Patient management and LTBI treatment in those with indeterminate QFT pretransplant should account for epidemiological risk factors, and shared decision-making is recommended.