Diagnostics for Fungal Infections in Solid Organ Transplants (SOT)

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

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Risk of infection associated with targeted therapies for solid organ and hematological malignancies

Therapeutic Advances in Infectious Disease ◽

10.1177/2049936121989548 ◽

2021 ◽

Vol 8 ◽

pp. 204993612198954

Author(s):

Isabel Ruiz-Camps ◽

Juan Aguilar-Company

Keyword(s):

Hematological Malignancies ◽

Opportunistic Infections ◽

Respiratory Infections ◽

Fungal Infections ◽

Checkpoint Inhibitors ◽

Janus Kinase ◽

Prolonged Treatment ◽

Solid Organ ◽

Risk Of Infection ◽

Increased Risk

Higher risks of infection are associated with some targeted drugs used to treat solid organ and hematological malignancies, and an individual patient’s risk of infection is strongly influenced by underlying diseases and concomitant or prior treatments. This review focuses on risk levels and specific suggestions for management, analyzing groups of agents associated with a significant effect on the risk of infection. Due to limited clinical experience and ongoing advances in these therapies, recommendations may be revised in the near future. Bruton tyrosine kinase (BTK) inhibitors are associated with a higher rate of infections, including invasive fungal infection, especially in the first months of treatment and in patients with advanced, pretreated disease. Phosphatidylinositol 3-kinase (PI3K) inhibitors are associated with an increased risk of Pneumocystis pneumonia and cytomegalovirus (CMV) reactivation. Venetoclax is associated with cytopenias, respiratory infections, and fever and neutropenia. Janus kinase (JAK) inhibitors may predispose patients to opportunistic and fungal infections; need for prophylaxis should be assessed on an individual basis. Mammalian target of rapamycin (mTOR) inhibitors have been linked to a higher risk of general and opportunistic infections. Breakpoint cluster region-Abelson (BCR-ABL) inhibitors are associated with neutropenia, especially over the first months of treatment. Anti-CD20 agents may cause defects in the adaptative immune response, hypogammaglobulinemia, neutropenia, and hepatitis B reactivation. Alemtuzumab is associated with profound and long-lasting immunosuppression; screening is recommended for latent infections and prevention strategies against CMV, herpesvirus, and Pneumocystis infections. Checkpoint inhibitors (CIs) may cause immune-related adverse events for which prolonged treatment with corticosteroids is needed: prophylaxis against Pneumocystis is recommended.

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Impact of fungal infections on solid-organ transplant recipients

Clinical Microbiology Newsletter ◽

10.1016/j.clinmicnews.2005.08.001 ◽

2005 ◽

Vol 27 (16) ◽

pp. 123-126 ◽

Cited By ~ 2

Author(s):

Mari Mizuta ◽

Emily A. Blumberg

Keyword(s):

Fungal Infections ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Solid Organ Transplant Recipients

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Abdominal Aortic Aneurysm Repair in Renal and Liver Transplant Recipients

Vascular and Endovascular Surgery ◽

10.1177/1538574419880673 ◽

2019 ◽

Vol 54 (1) ◽

pp. 51-57

Author(s):

Sobath Premaratne ◽

Jonathan Hopkins ◽

Martin Duddy ◽

Ket Sang Tai ◽

Mark Kay ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Liver Transplant ◽

Organ Transplant ◽

Abdominal Aortic Aneurysm Repair ◽

Solid Organ ◽

Organ Transplants ◽

Abdominal Aortic ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair

Background: Abdominal aortic aneurysm (AAA) repair in patients with organ transplant remains a challenge. We looked at AAA repair in patients with organ transplants at our tertiary liver and kidney transplant unit. Methods: A retrospective analysis of a prospectively maintained database was undertaken from January 2008 to July 2018. We looked at patient demographics, type of repair, and technical success including reinterventions, perioperative transplant organ function, and 30-day and 1-year survival rate. Eight of 662 patients who underwent AAA repair had a solid organ transplant. Of these, 5 were kidney transplants, 2 liver transplants, and 1 had kidney and liver transplant; 75% were male; and average age was 63.4 (range: 49-83). All patients had asymptomatic AAAs, and 6 were treated with standard endovascular repair, 1 standard repair with iliac branch device, and 1 open repair. Adjunctive techniques such as CO2 angiograms, deployment of main body through contralateral iliac, low-profile sheaths, custom-made stent grafts, and temporary axillo-femoral shunting were used to protect transplant organs. Thirty-day survival was 100% with 1 death at 5 months from liver failure, and 1 patient has a persistent type-2 endoleak 3 years after the procedure. Conclusion: Abdominal aortic aneurysm repair in patients with organ transplants can be undertaken using adjunctive endovascular and open surgical techniques.

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Post-transplant malignancies in solid organ recipients: development mechanisms and risk factors

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/1995-1191-2021-3-192-197 ◽

2021 ◽

Vol 23 (3) ◽

pp. 192-197

Author(s):

A. V. Nikulin ◽

I. V. Pashkov ◽

Y. S. Yakunin

Keyword(s):

Risk Factors ◽

General Population ◽

Life Expectancy ◽

Gradual Increase ◽

International Agency ◽

Solid Organ ◽

Organ Transplants ◽

Post Transplant

According to the International Agency for Research on Cancer, there were an estimated 19,292,789 new cancer cases in various localizations and 9,958,133 cancer deaths worldwide in 2020. These frightening figures clearly show that malignancies among the population is a pressing matter. The risk of post-transplant malignancy in solid organ recipients is 2–6-times higher than in the general population. Given the steadily increasing number of solid organ transplants worldwide and the gradual increase in life expectancy among organ recipients, studying the issues concerning risk factors and development mechanisms becomes a crucial task.

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Bacterial and Fungal Co-infections with SARS-CoV-2 in Solid Organ Recipients, A Retrospective Study

10.21203/rs.3.rs-244333/v1 ◽

2021 ◽

Author(s):

Mojtaba Shafiekhani ◽

Zahra Shekari ◽

Arash Boorboor ◽

Zahra Zare ◽

Sara Arabsheybani ◽

...

Keyword(s):

Antimicrobial Agents ◽

Fungal Infections ◽

Binary Logistic Regression ◽

Risk Groups ◽

Solid Organ ◽

Binary Logistic Regression Model ◽

Kidney Recipients ◽

Susceptible Patient ◽

Liver And Kidney ◽

Vancomycin Resistant

Abstract Background SARS-CoV-2, a novel corona virus, has caused clusters of fatal pneumonia worldwide. Immune compromised patients are among the high risk groups with poor prognosis of the disease. The presence of bacterial or fungal co-infections with SARS-CoV-2 is associated with increased mortality.Methods The electronic data of the liver and kidney recipients, hospitalized in COVID-19 intensive care unit in an 8-month period in 2020 were retrospectively assessed. The documented bacterial or fungal infections alongside with outcome and risk factors were recorded and analyzed by binary logistic regression model and multivariate analyses.Results Sixty-Six liver and kidney recipients were included this study. Twenty one percent of the patients had at least one episode of co-infection during their COVID-19 course. Bacterial and fungal co-infections contributed to a significantly higher mortality. Urine and sputum were the most common sites of pathogen isolation (45.45 % and 36.36%; respectively). The majority of infections were caused by vancomycin- resistant Enterococci (30%). Escherichia coli stood in the next position with 23.3%. Prior hospitalization and high does corticosteroid use were associated with co-infections (p=0<0.001 and p=0.02; respectively.)Conclusions Bacterial and fungal co-infections with COVID-19 are more prevalent on solid organ recipients compared to the general population. Prior hospitalizations and use of broad-spectrum antimicrobial agents leads to emergence of multi-drug resistant pathogens in this susceptible patient population. Early detection and treatment of co-infections as well as antibiotic stewardship is recommended in solid organ recipients.

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