Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with COVID-19. Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families including Coronaviridae. Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury and decreased quantification of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.

CAR T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, though 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 following CAR-T therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal screening, prophylaxis, and preemptive treatment strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR-T therapy for Non-Hodgkin's lymphoma (NHL) between December 2017 and September 2021 (n=280). Patients did not receive routine anti-yeast or mold prophylaxis. Proven and probable IFD was identified between day of cell infusion and last follow up. Cumulative Incidence Functions were calculated at 100 days and 18 months based on time to IFD using dates of IFD-free death, initiation of salvage treatment following relapse, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia (PJP), 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). Five infections (3 IMI; 2 IYI) occurred prior to day 100 and the 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% CI 0.8 - 4.4%). Amongst the 280 patients, many developed early toxicity including CRS (85%) and ICANS (55%). Late toxicities after day 30 including grade 3/4 neutropenia (41%), hypogammaglobulinemia (35%), and low CD4 T-cell count (20%) were common. IFD was rare amongst patients who received CD19 CAR-T therapy for NHL in the absence of routine antifungal prophylaxis despite frequent toxicities including CRS, ICANS, and late neutropenia. This study suggests that in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.

No abstract

No abstract

No abstract

No abstract

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients. Summary A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients. Conclusion This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed.

Background SARS-CoV-2 vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), but immunogenicity may be reduced in patients undergoing hematopoietic stem cell transplantation (HSCT). The variables that impact the humoral response, such as age, gender, disease and transplant type, prior treatments, and vaccine type, have not been comprehensively described. Methods A retrospective review was conducted at a single-centre of HSCT recipients who received COVID-19 vaccinations between 2020 and 2021. Participants were included if >18 years and had received at least a single dose of Pfizer, Moderna or Johnson & Johnson (J&J) vaccine. Anti-Spike (S) IgG titers were quantitatively measured at provider discretion during routine care using the Roche Elecsys Anti-SARS-CoV-2 spike immunoassay and categorized as Responders (< 0.8U/mL) and Non-responder (>0.8). Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for Responders vs Non-responders. Controlled risk factors included; Age, disease, treatments, and history of graft-versus-host disease (GVHD). Results Of 117 HSCT patients assessed, 59 (50.4%) were female, 106 (90.6%) were white, and the median age was 62.5 years (interquartile range [IQR, 49.9-67.8). Vaccinations were administered at a median of 179 days post-transplant (IQR 319 - 105) and antibody responses were measured at a median of 135.5 days post-vaccination (IQR 190-50). 106(90.6%) were responders with a mean titre of 1141.5U/mL (SD=1095.3). 35% had Low (< 100U/mL) titres. Being Female (OR 0.02, 95%CI 0.003 - 0.6) was associated with a slightly higher odds of being a responder. Conclusion Hematopoietic stem cell transplant recipients demonstrated a high prevalence of anti-S IgG antibody positivity following COVID vaccination. However, neither patient characteristics nor treatment regimens were seen to be strongly associated with anti-S protein positivity among HSCT recipients. More studies are needed to further characterize patient and treatment characteristics that correlate with seroprotection among these patients. Disclosures Stephen R. Walsh, MD, Janssen Vaccines: Grant/Research Support|ModernaTX: Grant/Research Support|Sanofi Pasteur: Grant/Research Support.