An open-label phase II trial of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity.

Background: Immunocompromised individuals have a limited humoral immune response to SARS-CoV-2 vaccination and are at higher risk of severe COVID-19. Sotrovimab is a monoclonal antibody (mAb) targeting a conserved SARS-CoV-2 spike protein epitope.

Methods: This phase II open-label study evaluated the safety and tolerability of sotrovimab pre-exposure prophylaxis in immunocompromised adults with impaired vaccine response.

Urine Cell-Free RNA vs Plasma Cell-Free RNA for Monitoring of Kidney Injury and Immune Complications.

Background: There is increasing interest in the use of circulating cell-free RNA (cfRNA) in plasma as an analyte for diagnosing and monitoring disease. While it is known that cfRNA can also be isolated from urine, the diagnostic potential of urine cfRNA, particularly relative to plasma cfRNA, remains underexplored.

Methods: Matched plasma and urine were collected from hematopoietic stem cell transplant (HSCT) recipients (n = 24), immune-checkpoint-inhibitor (ICI) recipients with or without acute kidney injury (AKI) (n = 46), and healthy volunteers (n = 5), yielding 297 samples.

Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection or Disease or with Concurrent Organ Dysfunction: A Phase 2 Open Label Study.

Introduction: Refractory or resistant cytomegalovirus (CMV) infection and disease pose a significant challenge in immunocompromised patients, including solid organ transplant (SOT) and allogeneic hematopoietic cell transplant (allo-HCT) recipients. This study aimed to evaluate letermovir as a treatment for patients with CMV infection or disease.

Methods: We performed an open-label, phase II non-randomized clinical trial.

Peritoneal Tuberculosis in a Patient on Tumor Necrosis Factor inhibitors: A Case Report and Review of the Literature.

Peritoneal tuberculosis (PTB) is a diagnostic challenge due to its nonspecific presentation, low sensitivity of ascitic fluid microbiologic tests, and possible resemblance to peritoneal carcinomatosis. We describe a case of 51-year-old woman with long-term tumor necrosis factor alpha (TNF-α) inhibitor exposure presented with fever and abdominal distension after returning from the Philippines. Initial tests, including microbiological studies, were inconclusive, despite imaging findings suggestive of carcinomatosis with elevated CA-125.

A Scoping Review of Arthropod-Borne Flavivirus Infections in Solid Organ Transplant Recipients.

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.

Plasma Cell-Free RNA Captures Immune Dynamics and Predicts GVHD after Hematopoietic Stem Cell Transplantation.

Despite long-standing success of hematopoietic stem cell transplantation (HSCT) in the treatment of blood cancers and severe immune disorders, monitoring post-transplant complications remains challenging, in part because of the limited availability of informative molecular tests. Here, we evaluated the utility of cell-free RNA (cfRNA) in plasma as an analyte to monitor HSCT recipients and predict immune-related complications. We used RNA-sequencing to profile cfRNA in 549 plasma samples collected at predetermined time points from allogeneic HSCT recipients at two transplant centers.

Safety and tolerability study of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity.

Background: Multiple vaccines have been approved since August 2021 to prevent infection with SARS-CoV-2; however, 20-40% of immunocompromised people fail to develop SARS-CoV-2 spike antibodies after COVID-19 vaccination and remain at high risk of infection and more severe illness than non-immunocompromised hosts. Sotrovimab (VIR-7831) is a monoclonal neutralizing antibody that binds a conserved epitope on the SARS-CoV-2 spike protein. It is neither renally excreted nor metabolized by P450 enzymes and therefore unlikely to interact with concomitant medications (e.

Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Immunogenicity among Chimeric Antigen Receptor T Cell Therapy Recipients.

Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted.

The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study.

Background: Methicillin-susceptible (MSSA) is a common cause of bloodstream infection (BSI) in patients with febrile neutropenia, but treatment practices vary, and guidelines are not clear on the optimal regimen.

Methods: We conducted a multicenter retrospective cohort study of MSSA BSI in febrile neutropenia. We divided patients into 3 treatment groups: (1) broad-spectrum beta-lactams (ie, piperacillin-tazobactam, cefepime, meropenem); (2) narrow-spectrum beta-lactams (ie, cefazolin, oxacillin, nafcillin); and (3) combination beta-lactams (ie, both narrow- and broad-spectrum).

Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.

CAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated.

Clarithromycin-Rifampin-Based Treatment for Nontuberculous Mycobacteria Infections in Immunocompromised Patients who Require Concomitant CYP-Metabolized Medications.

Clarithromycin (CYP inhibitor) can be used instead of azithromycin for nontuberculous mycobacteria therapy in patients requiring CYP substrates to mitigate rifampin's CYP induction. We found no differences in adverse events (10/13 vs 14/17;  = .73), drug intolerability (1/5 vs 4/11;  = 1), or 90-day mortality (0/13 vs 1/17;  = 1) in patients receiving clarithromycin vs azithromycin.

Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib.

Gilteritinib is primarily metabolized via cytochrome P450 (CYP). Therefore, concomitant administration of strong CYP3A4 inducers or inhibitors is not recommended. We evaluated the incidence of gilteritinib-related adverse events (AEs) in 47 patients who received gilteritinib with or without antifungal triazoles which are known inhibitors of CYP3A4.