Transplant Infectious Disease最新文献

Background: Coccidioidomycosis is a fungal infection that poses a serious risk when transmitted through organ transplantation. We analyzed cases reported to the Organ Procurement and Transplantation Network ad hoc Disease Transmission Advisory Committee from 2013 to 2022.

Methods: Donors and/or recipients who had positive Coccidioides immitis/posadasii serology, pathology, and/or culture were included in this study. Cases adjudicated as 'proven' or 'probable' were analyzed for donor infection risk factors, the timing of infection, transmission by organ type, clinical manifestations, and recipient outcomes. Patient and facility identifiers were removed prior to review.

Results: During this time period, 73 potential instances of Coccidioides donor disease transmission events were reported. Among them, infection was transmitted from seven deceased donors to eight recipients. All seven deceased donors had prior infection or exposure to regions where coccidioidomycosis is endemic. Of 20 individuals receiving organs from these donors, eight developed infection, resulting in a 40% transmission rate. The median time to diagnosis post-transplant was 39 days. Disseminated disease occurred in six recipients, five of whom died from the infection. Notably, none of the recipients who received prophylactic antifungal treatment died from the infection.

Conclusion: Despite its rarity, donor-derived Coccidioides infection is a serious concern, particularly due to the high mortality rate in the early post-transplant period. To mitigate these risks, a thorough assessment of donor exposure history, coupled with donor serology and bronchoalveolar lavage cultures, can effectively guide post-transplant antifungal prophylaxis. Prompt reporting is crucial to prevent Coccidioides infections among other recipients.

Background: Despite limited data supporting use in solid organ transplant (SOT) recipients, atovaquone and dapsone are often used as alternatives to trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis.

Methods: This single-center, retrospective cohort study describes a multi-organ program's experience with alternative PJP prophylaxis. Adult SOT recipients transplanted November 13, 2020 to November 13, 2022 who received non-TMP-SMX PJP prophylaxis and had > 1 year follow-up were included.

Results: Among 953 SOTs performed, 333 (34.9%) recipients received alternative PJP prophylaxis (319 [95.8%] atovaquone and 14 [4.2%] dapsone). Alternative prophylaxis was initiated in 76 (22.8%) recipients without starting TMP-SMX, mostly due to sulfa allergy (62, 81.6%). In 257 recipients who started TMP-SMX, common reasons for switching to alternatives were hyperkalemia (105, 40.9%) and leukopenia (77, 30.0%). While 79.8% of recipients had these adverse effects resolve, only 27.3% resumed TMP-SMX. Tolerance was high after resumption (85.7%). Barriers to accessing alternative prophylaxis included cost (25, 7.5%) and prior authorizations (26, 7.8%). There was one case of severe disseminated toxoplasmosis, one case of Nocardia infection, and no cases of PJP.

Conclusion: Alternative PJP prophylaxis carries risk of breakthrough infection and barriers to initiation. Since most recovered from adverse effects of TMP-SMX and tolerated resumption, providers should re-trial TMP-SMX when feasible.

Background: Donor screening and antimicrobial management processes are inconsistent across organ procurement organizations (OPOs) and transplant centers. As part of a Controversies Conference addressing the evaluation and management of infectious diseases (ID) in deceased donors sponsored by the American Society of Transplantation (AST), two online pre-meeting surveys were developed to inform conference proceedings and assess current practices and opinions on donor screening and antimicrobial management.

Methods: Survey 1 addressed the current state of deceased donor ID testing, culture data communication, antimicrobial utilization, and involvement of transplant ID during donor management and was distributed to all 56 United States OPOs. Survey 2 evaluated transplant professionals' opinions regarding donor antimicrobial use and was sent to the AST Infectious Disease, Kidney Pancreas, Liver and Intestinal, and Thoracic and Critical Care Community of Practice listservs. Descriptive statistics were performed.

Results: Thirty-five (63%) unique responses were received from OPOs for Survey 1. Findings included variability in the timing of donor culture collection, frequent sampling of indwelling catheters, wide variation in the location of culture processing, and availability of additional susceptibility testing. Eighty-eight unique responses were received from approximately 1552 (6%) transplant providers for Survey 2. Of the respondents, 37% would not recommend standard antibiotics prior to organ recovery in the absence of suspected or confirmed infection.

Conclusions: These surveys demonstrate variability in donor testing, donor antimicrobial utilization, and transplant provider opinions regarding the need for and selection of antimicrobial agents. Findings highlight opportunities for standardized approaches to donor testing and management.

Background: Prior to the 2013 HIV Organ Policy Equity (HOPE) Act, which enabled research on the transplantation of solid organs from donors with human immunodeficiency virus (HIV) to candidates living with HIV, it was prohibited for HIV+ individuals to donate organs in the United States. In 2015, alongside the release of HOPE Act research criteria, the Organ Procurement and Transplantation Network (OPTN) made organ allocation policy and system changes to allow HIV+ to HIV+ transplantation.

Methods: The OPTN database was queried for all adult kidney registrations ever waiting from November 23, 2015, to December 31, 2022; the cohort was split into a HOPE cohort (ever willing to accept an HIV+ kidney) and a non-HOPE cohort (all remaining). Estimated median waiting times (eMWTs) were calculated using a period prevalent Kaplan-Meier approach; HOPE registrations were matched 1:5 without replacement to non-HOPE registrations using a logistic regression propensity score.

Results: Using all waiting time, the eMWT for the HOPE cohort was significantly lower than the matched non-HOPE cohort (3.04 years [95% confidence interval {CI}: 2.70, 3.41] versus 5.88 years [95% CI: 5.65, 6.18]). This trend persisted when estimating MWT using other active time and geographical definitions (ignoring geography and donor service area).

Conclusion: These results suggest that transplantation through the OPTN HOPE variance yields decreases eMWT, perhaps reducing the medium and longer-term impacts of living with HIV.

Background: Adenovirus (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.

Methods: This 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.

Results: We 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.

Conclusion: ADV 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.

Background: Outcomes after bebtelovimab treatment for COVID-19 were favorable for most but not all solid organ transplant recipients (SOTRs) during the era of Omicron BA.2 to BA.5, but effects of timing of bebtelovimab administration on these outcomes are unknown. We sought to compare outcomes of SOTR who received early bebtelovimab ("EBT", given ≤ 2 days from diagnosis) versus late bebtelovimab ("LBT", given between Days 3 and 7), versus no bebtelovimab (NBT).

Methods: This was a retrospective cohort study of SOTRs with mild-to-moderate COVID-19, with endpoint of 30-day COVID-19-related hospitalization. Multivariable logistic regression was performed to determine variables associated with receiving EBT, and to assess impact of EBT on hospitalization. A propensity score (PS) was calculated for EBT versus NBT.

Results: Of 297 SOTRs, 162 (58.1%) received EBT, 46 (16.5%) LBT, and 71 (25.4%) NBT. Early bebtelovimab treatment was associated with a lower risk of 30-day COVID-19-related hospitalization compared to NBT (OR, 0.112 [95% CI, 0.018-0.686]; p = 0.018). There was no significant difference in hospitalization risk between LBT and NBT, suggesting that delayed administration may not confer additional benefits over no treatment.

Conclusions: Early bebtelovimab treatment in outpatient SOTRs was associated with a lower risk of hospitalization compared to no treatment, while late administration did not show a significant advantage over no treatment. Although bebtelovimab is no longer authorized, these findings suggest that the timing of COVID therapies for SOTRs may be important to optimize outcomes.

Background: The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly.

Methods: A single-center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA.

Results: Over the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut-off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre-emptive treatment. Using a cut-off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient.

Conclusion: Serum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation.

BK polyomavirus (BKPyV) is an important opportunistic viral infection that complicates kidney transplantation. Uncontrolled viral replication may result in BKPyV-associated nephropathy (BKPyVAN), a major cause of premature allograft damage and failure. In the continued absence of proven treatments, management relies on the empirical reduction of immunosuppression to facilitate an effective host immune response to clear the virus. This may be complicated by the risk of allograft rejection. There is compelling evidence that cellular immune responses are key to establishing control after viral reactivation. Measurable peripheral BKPyV-specific T cell responses temporally correlate with declining viral loads and subsequent clearance. Conversely, these responses are delayed or absent in BKPyVAN. How these peripheral findings correspond to the intragraft response, and whether BKPyV-specific T cells contribute to the immunopathology of BKPyVAN, remains poorly understood. Molecular techniques have provided some insights; however, these have been unable to fully discriminate BKPyVAN from cellular rejection to date. Furthermore, the contributions of components of innate cellular immunity, such as natural killer cells, are not known. Herein, we review the role of cellular immunity in BKPyV infection in kidney transplant recipients. We discuss advances in the understanding of how the development, phenotype, and functionality of these responses may determine the balance between viral control and immunopathology, and how this knowledge is being translated into tools to prognosticate and guide individualized immunosuppression reduction. Lastly, we consider how further elucidation of these responses may inform the design of therapies that would revolutionize how BKPyV is managed after transplantation.

Background: A patient with an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM) and oxacillinase (OXA-48) producing Escherichia coli (E. coli) infection was awaiting orthotopic liver transplant. There is no standardized antibiotic prophylaxis regimen; however, in line with the Infectious Diseases Society of America guidance, an antibiotic prophylactic regimen of ceftazidime-avibactam 2.5 g TDS with aztreonam 2 g three times a day (TDS) IV was proposed.

Methods: The hollow fiber system (HFS) was applied to inform the individualized pharmacodynamic outcome likelihood prior to prophylaxis.

Results: A 4-log reduction in CFU/mL in the first 10 h of the regimen exposure was observed; however, the killing dynamics were slow and six 8-hourly infusions were required to reduce bacterial cells to below the limit of quantification. Thus, the HFS supported the use of the regimen for infection clearance; however, it highlighted the need for several infusions. Standard local practice is to administer prophylaxis antibiotics at induction of orthotopic liver transplantation (OLT); however, the HFS provided data to rationalize earlier dosing. Therefore, the patient was dosed at 24 h prior to their OLT induction and subsequently discharged 8 days after surgery.

Conclusion: The HFS provides a dynamic culture solution for informing individualized medicine by testing antibiotic combinations and exposures against the bacterial isolates cultured from the patient's infection. .