Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

Background: Individuals who are immunocompromised (IC) are at high risk for severe coronavirus disease 2019 (COVID-19).

Methods: Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020-April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety of casirivimab plus imdevimab (CAS + IMD) versus placebo in IC versus overall study patients.

Results: Ninety-nine of 1940 (5.

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.

Economic and clinical burden associated with respiratory viral infections after allogeneic hematopoietic cell transplant in the United States.

Background: Allogeneic hematopoietic cell transplant (allo-HCT) recipients are at increased risk for respiratory viral infections (RVIs), which invoke substantial morbidity and mortality. Limited effective antiviral options and drug resistance often hamper successful RVI treatment, creating additional burden for patients and the health care system.

Methods: Using an open-source health care claims database, we examined differences in clinical outcomes, health resource utilization, and total reimbursements during the 1-year period following allo-HCT in patients with and without any RVI infection (respiratory syncytial virus, influenza, parainfluenza virus, and human metapneumovirus).

Hepatitis B Virus Vaccination after Allogeneic Hematopoietic Cell Transplantation Prevents Post-Transplantation Hepatitis B Virus Reactivation.

Hepatitis B virus (HBV) reactivation in allogeneic hematopoietic cell transplantation (HCT) recipients with evidence of pretransplantation resolved HBV infection is an important cause of morbidity, usually occurring 1 year or later after HCT. We retrospectively studied a cohort of allogeneic HCT recipients with resolved HBV infection, some of whom were vaccinated for HBV following transplantation, to understand whether post-HCT HBV vaccination influenced the risk of HBV reactivation. The study included all patients with resolved HBV who underwent allogeneic HCT at our institution between January 1, 2000, and December 31, 2015, where HBV vaccination starting at 1 year after HCT became standard in 2012 and antiviral prophylaxis is not used.

Cytomegalovirus-related Complications and Management in Facial Vascularized Composite Allotransplantation: An International Multicenter Retrospective Cohort Study.

Background: There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation.

Methods: This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed.

Outcomes of antifungal prophylaxis for newly diagnosed AML patients treated with a hypomethylating agent and venetoclax.

Antifungal prophylaxis (AFP) is recommended for acute myeloid leukemia (AML) patients receiving the combination of venetoclax (VEN) and a hypomethylating agent (HMA), but the benefit of this practice is unclear. We identified 131 patients with newly diagnosed AML who received frontline VEN/HMA and evaluated the use of AFP and its association with invasive fungal infections (IFIs) and AML outcomes. Seventeen percent of our patients received AFP at any time.

Epidemiology and outcomes of invasive aspergillosis among pediatric immunocompromised patients: A 12-year single-center experience.

Unlabelled: Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019.

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.

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

Background: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions).

Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial.

Background: Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase.

Methods: In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up.

Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical Trial Design: Unintended Consequences for Prevention Trials?

Background: Consensus definitions for the diagnosis of invasive fungal diseases (IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical trials, for instance by increasing biomarker cutoff limits to define positivity. To date, there is a paucity of data as to the impact of the revised definitions on clinical trials.

Methods: In this study, we sought to determine the impact of the new definitions on classifying invasive aspergillosis (IA), the most common invasive mold disease in immunocompromised patients.

When to change treatment of acute invasive aspergillosis: an expert viewpoint.

Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice.

American Society for Transplantation and Cellular Therapy Series: #3-Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation.

The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious diseases guidelines for the care of hematopoietic cell transplant (HCT) recipients. A new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and answered FAQs.

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.

Full facial retransplantation in a female patient-Technical, immunologic, and clinical considerations.

There is limited experience with facial retransplantation (fRT). We report on the management of facial retransplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody-mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation.

Isavuconazole Treatment of Invasive Fungal Sinusitis: A Post Hoc Analysis of the SECURE and VITAL Trials.

This post hoc analysis of international phase III isavuconazole trials identified 50 patients (90% immunocompromised or diabetic) with invasive fungal sinusitis (88% mucormycetes, Aspergillus) who received isavuconazole as primary (n = 33) or salvage (n = 17) therapy for a median of 82 days (range, 2-882). Overall survival was 82% at day 42 and 70% at day 84.

Cytomegalovirus events in high-risk allogeneic hematopoietic-cell transplantation patients who received letermovir prophylaxis.

Letermovir is approved for the prevention of cytomegalovirus (CMV) reactivation and clinical disease in patients undergoing allogeneic hematopoietic-cell transplantation (HCT). However, there is uncertainty about letermovir's ability to prevent clinical events during the period of prophylaxis as well as after the discontinuation of prophylaxis in the post-transplant setting. We performed a retrospective cohort study in CMV-seropositive allogeneic HCT recipients at high risk of CMV events, who received letermovir for primary prophylaxis from November 2017 through December 2019.

Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease.

Invasive fungal disease (IFD) can be a severe treatment complication in patients with myeloid malignancies, but current risk models do not incorporate disease-specific factors, such as somatic gene mutations. Germline GATA2 deficiency is associated with a susceptibility to IFD. To determine whether myeloid gene mutations were associated with IFD risk, we identified 2 complementary cohorts of patients with myeloid malignancy, based on (1) the diagnosis of invasive aspergillosis (IA), or (2) the presence of GATA2 mutations identified during standard clinical sequencing.

DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study.

Background: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.

Methods: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.

Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity.

Background: Coronavirus disease 2019 (COVID-19) primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell-, tissue-, and organ-specific injury due to COVID-19.

Methods: Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma.

Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation.

Background: Cutaneous changes of facial vascularized composite allotransplants (fVCAs) are extensively described in the literature. Parts of the nose, nasal, and oral cavities are included in most fVCAs. Distinctively, the nose and mouth are lined by mucosa.