Transplant Infectious Disease最新文献

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. .

Arthropod-borne flaviviruses (ABFs), transmitted by mosquitoes or ticks, are increasing due to climate change and globalization. This scoping review examines the epidemiology, clinical characteristics, diagnostics, treatment, and outcomes of ABF infection in solid organ transplant recipients (SOTRs). A database search up to January 25, 2024, focused on ABFs such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), Powassan virus (POWV), yellow fever virus (YFV), and Zika virus (ZIKV), limited to SOTRs. We identified 173 WNV cases from 84 studies, with 28 donor-derived infections (DDIs). Common clinical features included fever (78.5%), altered mental status (65.1%), and weakness or paralysis (45.6%). Treatment involved reducing immunosuppression (IS) in 93 cases, with intravenous immunoglobulin (IVIG), interferon alfa-2b, and ribavirin used in 75 cases. Seven cases involved graft loss or rejection post-infection. WNV infection had a 23.7% mortality rate, with severe neurological complications in 43.9% For DENV infection, 386 cases from 47 studies were identified, including 14 DDI cases. Symptoms included fever (85%), myalgias (56.4%), and headache or retro-orbital pain (34.6%). Severe dengue occurred in 50 cases (13.0%). IVIG was administered in six cases. Reduction in IS was reported in 116 patients. DENV mortality rate was 4.9%. Additionally, 26 cases of less common ABFs such as JEV, POWV, YFV, and ZIKV were described. In summary, ABF infections among SOTRs are associated with higher morbidity and mortality compared to the general population, emphasizing the need for improved preventive strategies, timely diagnosis, and optimized management protocols.

Background: Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients.

Methods: A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed.

Results: Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1 mg/L for those who were therapeutic and 0.4 mg/L for those who were not (p < 0.001). The median cumulative dose was 2000 mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33% vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy.

Conclusion: Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400 mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.

Background: Belatacept is a costimulatory blocker that can be used to prevent and treat rejection in lung transplant recipients (LuTRs). The epidemiology of infections in belatacept-treated LuTRs has not been systematically evaluated.

Methods: We performed a single-center retrospective study of all adult LuTRs who received belatacept as prevention or treatment of antibody-mediated rejection (desensitization) or as part of maintenance immunosuppression from January 1, 2011, to June 30, 2022. We assessed the epidemiology of infections that occurred within 12 months following the first belatacept dose.

Results: Fifty-two LuTRs received at least one dose of belatacept as either desensitization (n = 32) or maintenance immunosuppression (n = 20). Among 45 patients who were cytomegalovirus (CMV) donor and/or recipient seropositive, nine (20%) developed CMV infection. Seven (77%) CMV infections occurred despite valganciclovir prophylaxis and four (44%) were associated with antiviral resistance. Three (6%) LuTRs developed Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (PTLD). Twenty-five (48%) LuTRs developed 43 bacterial infections and five (10%) developed proven or probable invasive fungal disease. Incidence rates of viral, bacterial, and fungal infections were similar between the desensitization and maintenance groups: incidence rate ratios (95% confidence interval) were 0.70 (0.32-1.57), 1.31 (0.70-2.46), and 2.82 (0.31-25.2), respectively. Infection/PTLD prompted belatacept discontinuation in eight (15%) patients.

Conclusions: In the first year after belatacept initiation, LuTRs commonly developed CMV infections, EBV+ PTLD, and bacterial infections. Multicenter collaborations are needed to better understand infection risks in LuTRs treated with belatacept.

Background: Donor-derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022.

Methods: Initially, screening was done via dengue immunoglobulin M (IgM), targeting donors with specific clinical criteria (thrombocytopenia, drop in platelet count, prolonged prothrombin time/partial thromboplastin time, and discretion of the transplant team), later transitioning to blood dengue reverse transcription-polymerase chain reaction (RT-PCR) in 2007 with similar criteria, and subsequently universal screening in 2016. In 2021, urine dengue RT-PCR was added following a case of donor-derived dengue infection from an aviremic but viruric donor.

Results: Out of 431 potential deceased donors, 395 (91.6%) underwent dengue screening, with six (1.5%) testing positive for dengue. In 2006, three positive screens were identified: two through dengue IgM and one via blood dengue RT-PCR; subsequent years saw one positive screen each in 2007, 2008, and 2019 via blood dengue RT-PCR. Potential deceased donors with a positive blood dengue screen were rejected as solid organ and tissue donors. Those with negative blood dengue RT-PCR but positive urine dengue RT-PCR would be rejected as kidney donors, but the use of other organs and tissues was at the discretion of the transplantation team.

Conclusion: The optimal screening protocol remains uncertain, but our findings suggest that a universal screening strategy utilizing both blood and urine dengue RT-PCR could be considered in dengue-endemic countries.

Over 118 million blood donations are collected globally each year. Recipients of blood products include those who experience major trauma or surgery, have acute blood loss and anemia, or impaired bone marrow function. Solid organ transplant recipients often require transfusion of blood products which places them at risk of transfusion-associated adverse events including transfusion-transmitted infection. National hemovigilance networks have documented low rates of transfusion-transmitted infection in the general population. Incidence transfusion-transmitted infection continues to occur in solid organ transplant patients and arises mainly from existing gaps in blood donor biovigilance processes. Emerging infectious diseases have highlighted existing gaps in the donor-recipient pathway to administering safe blood products. This article reviews the current process and regulatory oversight of blood donor biovigilance, including donor screening and microbiological testing, highlights cases of transfusion-transmitted infection documented in the literature, and addresses ways in which biovigilance may be improved, with a focus on the impact of solid organ transplantation.

Aim: Often, organ transplantation is the only option to improve the life expectancy and quality of life of patients with terminal organ failure. Despite improved donor and organ assessment, a residual risk remains for transmitting infection, tumor, or other disease from the donor to recipients. Analysis, reporting, and managing of donor-derived diseases through a vigilance and surveillance system (V&S) is mandatory in many countries. We report on suspected and proven/probable donor-derived infections (DDI) in Germany over a period of 8 years (2016-2023).

Methods: All incoming serious-adverse-event and serious-adverse-reaction (SAE/SAR) reports from 01.01.2016 to 31.12.2023 were evaluated for suspected DDI. Analysis of imputability followed the definition of the US Disease Transmission Advisory Committee (DTAC). Only probable and proven cases according to DTAC classification were defined as DDI.

Results: During the study period, 9771 donors in Germany donated post-mortem organs to 27 919 recipients. In that period 612 SAE/SAR cases were reported, 377 (62%) involved infections. 41 cases were proven/probable DDI affecting 58 recipients (seven recipients died, 12%). Suspected infections were bacterial (182/377, 48%), fungal (135/377, 36%), viral (55/377, 15%), and parasitic (5/377, 1%). In case of bacterial DDI, no recipient died, but organ loss occurred in six recipients. In case of fungal or viral DDI, 19% (3/16) and 21% (3/14) of the recipients died, respectively.

Conclusions: DDI are rare in solid organ transplantation (58/27 919, 0.21%), but when they occur, they are associated with high morbidity and mortality in affected recipients. Careful and detailed donor evaluation and a reliable V&S help improve recipient safety.