Zinplava (bezlotoxumab) / Merck (MSD) - LARVOL DELTA

ICON-2: FMT and Bezlotoxumab Compared to FMT and Placebo for Patients With IBD and CDI (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Brigham and Women's Hospital | Active, not recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Transplantation

Bezlotoxumab As Treatment for Recurrent/Chronic Clostridioides Difficile Infection in Stem Cell Transplant Recipients (ASH 2024) - "However, the safety and efficacy of bezlotuxumab has not been studied in pediatric patients undergoing a SCT, and no data exists to detail its impact on common immunosuppressants such as tacrolimus and mycophenolate mofetil (MMF)...Following relapse of AML, the patient enrolled on a clinical trial to receive a KMT2A inhibitor, revumenib, achieved remission, and eventually proceeded to a second SCT using a single cord donor. The patient's post-SCT course was complicated by Streptococcus mitis/oralisbacteremia, resulting in a long course of broad-spectrum antibiotics with vancomycin and meropenem...At this recurrence, she was hospitalized for dehydration and treated with oral vancomycin, subsequently transitioning to oral fidaxomicin over a 21-day taper...All patients were confirmed to have no gastrointestinal GVHD causing the diarrhea, and no recurrence of diarrhea occurred after bezlotoxumab. This case series strongly suggests the potential utility of bezlotoxumab..."

Clinical • Acute Myelogenous Leukemia • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pediatrics • Pneumonia • Respiratory Diseases • Transplantation • DEK • KMT2A • NUP214

The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice. (PubMed, PLoS Pathog) - "These findings demonstrate that AZD5148 offers broad-spectrum protection against C. difficile strains and retains in vivo efficacy even in the absence of in vitro neutralization. Its distinct mechanism of action and superior potency compared to bezlotoxumab support its continued development as a promising therapeutic candidate for the prevention of a first CDI episode and prevention of recurrence."

Journal • Preclinical • Infectious Disease

Efficacy of Bezlotoxumab in Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis (ACG 2025) - "The review includes a total of 10 articles that assessed the recurrence rates of CDI infectionfollowing BZX infusion and standard care. There were 2926 patients in the BZX administrationgroup and 2638 patients of the control group. The primary outcome assessed was the oddsratio of recurrence of CDI infection between the 2 groups , the odds of a recurrence of CDI wassignificantly lower in the BZX infusion group in comparison to the standard treatment protocol(OR = 0.59 (0.54; 0.65) , 95% CI; p = 0.67 , I^2 = 0%)."

Retrospective data • Review • Infectious Disease

The Colitis Conundrum: Recurrent C. difficile and CMV Colitis in a Patient With Underlying Ulcerative Colitis (ACG 2025) - "Prior C. diff infections were resistant to vancomycin and metronidazole, only improving with fidaxomicin...He was treated with Bezlotoxumab, but follow-up colonoscopy with biopsy showed pancolitis with CMV-infected cells...He also failed UC treatment with infliximab...Colonoscopy after treatment with fecal live-brpk capsules, ganciclovir, and upadacitinib. Rectosigmoid junction shows quiesced inflammation with endoscopic healing."

Clinical • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy of Fecal Microbiota Transplant for Prevention of Recurrent CDI in Patients Diagnosed With Cancer (ACG 2025) - "Vancomycin and fidaxomicin were the most frequently used antibiotics, and 18.8% received bezlotoxumab.Colonoscopy-delivered FMT was the most common intervention (68.1%), followed by Rebyota (17.4%) and VOWST (7.2%); combination strategies were used in 7.2%. A total of 69 patients with a history of CDI or rCDI were included. Hematologic malignancies were the most common cancer type (29.6%), and nearly half had stage III–IV disease. At the time of their most recent CDI episode, 55% were receiving active cancer therapy."

Clinical • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Oncology • Transplantation

Declining Mortality From Clostridioides difficile Infection Following Therapeutic Innovation: A 25-Year National Analysis (ACG 2025) - "Introduction: The introduction of fidaxomicin, bezlotoxumab, and fecal microbiota-based therapies marks a new era in the management of Clostridioides difficile infection (CDI). CDI mortality rose more than 10-fold during the pre-therapeutic era (1999–2010), from 599 deaths in 1999 to 6,877 in 2010 (average: 4,055/year). The post-therapeutic era (2011–2023) began with a peak of 7,672 deaths in 2011, followed by a sustained decline to 3,680 deaths/year (average, 2020–2023)- a 52% reduction. Five epidemic phases were observed: early epidemic (1999–2003), peak epidemic (2004–2008), therapeutic transition (2009–2013), post-therapeutic plateau (2014–2018), and recent decline (2019–2023)."

Infectious Disease

Risk Factors for Nosocomial Clostridioides Difficile Infection-Induced Diarrhea in Patients Receiving Enteral Feeding: A Scoping Review. (PubMed, J Hosp Infect) - "EF may contribute to CDI risk through its impact on gut microbiota and related factors. While certain EF strategies show potential benefits, further research is needed to determine their role in CDI prevention and to develop evidence-based nutritional guidelines for at-risk patients."

Journal • Review • Infectious Disease • Transplantation

Bezlotoxumab for the prevention of recurrent Clostridioides difficile infection for patients with cancer. (PubMed, Ann Gastroenterol) - "Bezlotoxumab was administered a median of 10 days (interquartile range [IQR] 5-12.5) after symptom onset, and fidaxomicin was the most frequently used concurrent antibiotic (41.2%). Bezlotoxumab demonstrated high efficacy in reducing rCDI within a 90-day period after administration, compared to rates in the non-cancer population. The findings suggest that administration of bezlotoxumab for rCDI prevention should be considered, given the improvement in the outcome of this high-risk group."

Journal • Infectious Disease • Oncology • Transplantation

What Can We Learn from Bezlotoxumab: A Retrospective Evaluation of Practice Patterns (IDWeek 2025) - No abstract available

Retrospective data • Infectious Disease

Bezlotoxumab as Treatment for Recurrent/Chronic Clostridioides difficile Infection in Pediatric Stem Cell Transplant Recipients: A Multi-Institutional Experience. (PubMed, Pediatr Blood Cancer) - "Here, we describe a series of cases where bezlotoxumab was used in conjunction with antibiotic therapy to effectively treat recurrent CDI in pediatric SCT patients. Bezlotoxumab was not associated with increased adverse events, did not impact management of graft-versus-host disease, and was safe to use in pediatric patients in the peri-transplantation period."

Journal • Graft versus Host Disease • Immunology • Infectious Disease • Oncology • Pediatrics • Transplantation

Epitope conservation of AZD5148, a broadly neutralizing anti-Toxin B monoclonal antibody, among diverse and global contemporary Clostridioides difficile isolates. (PubMed, J Infect Dis) - "Our comprehensive analysis of global sequences found the AZD5148 epitope to be highly conserved, and thus unlikely to be impacted by most of the genotypic variations in recently circulating C. difficile ribotypes and STs."

Journal • Infectious Disease

Making Sense of Differing Guidelines for Clostridioides difficile Infection. (PubMed, Infect Dis Clin North Am) - "Therapeutically, guideline recommendations more recently have favored fidaxomicin and incorporated immune-based therapies and microbial restoration therapies. As treatment options and guideline recommendations change, it is imperative to understand why these recommendations have evolved and understand current best diagnostic and therapeutic practices in managing CDI."

Journal • Review • Infectious Disease • Transplantation

Losing an Effective Tool in the Fight Against Clostridioides difficile: Bezlotoxumab Improves Outcomes in Transplant Recipients (WTC 2025) - "This study evaluates its efficacy in solid organ transplant (SOT) recipients with C. diff infection, assessing its impact on sepsis, hospitalizations, mortality, and recurrence within 30 days post-infection compared to standard antibiotic therapy alone.* This was a retrospective, propensity score-matched case-control study using the TriNetX database to compare 30-day outcomes of SOT recipients with C. diff infection treated with standard of care therapy (vancomycin or fidaxomicin) with (BEZ) or without (no BEZ) bezlotoxumab. Propensity score matching (1:1) was performed based on demographics, comorbidities, diagnosis of heart failure, hypoalbuminemia, inflammatory bowel disease, SOT type, immunosuppressive medications, and use of proton pump inhibitors, clindamycin, or ampicillin... Bezlotoxumab was associated with significantly reduced sepsis, mortality, recurrent C. diff infection, and hospitalizations in transplant recipients, supporting its role as an adjunct therapy..."

Clinical • Cardiovascular • Congestive Heart Failure • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Septic Shock • Solid Organ Transplantation • Transplantation

Clostridioides difficile Infection Management Optimization in Solid Organ Transplant Recipients (WTC 2025) - "*Purpose: Fidaxomicin (FM) is the preferred therapy for initial and subsequent Clostridioides difficile infection (CDI) episodes due to its potential to reduce recurrence rates compared to vancomycin (VM)...ID recommended bezlotoxumab in 27%, 33%, and 40% of 1st episodes, 1st, and subsequent recurrences respectively.* Identified root causes of guideline noncompliance included provider comfort in prescribing VM treatment , lack of guideline awareness among non-transplant providers, and limited familiarity with the CDI order set. Identified root causes of guideline noncompliance included provider comfort in prescribing VM treatment , lack of guideline awareness among non-transplant providers, and limited familiarity with the CDI order set. Proposed interventions include CDI order set education and guidance among transplant and other specialties, and distribution of an infographic to case management to optimize awareness of available resources for co-pay assistance. Plan..."

Clinical • Infectious Disease • Solid Organ Transplantation • Transplantation

Clinician Management Preferences for Clostridioides difficile Infection in Adults: A 2024 Emerging Infections Network Survey. (PubMed, Open Forum Infect Dis) - "Additionally, 72% (357/498) reported that their institutional guidelines recommended vancomycin as the first-line agent. The most common barrier to fidaxomicin use was challenges with outpatient insurance coverage (82% [408/496]). Bezlotoxumab was available to 74% (370/500) of respondents, though 33% (165/497) indicated they do not use bezlotoxumab routinely...Fecal microbiota live-jslm was available to 36% (179/500), and fecal microbiota spores live-brpk was available to 30% (150/500). Significant barriers, including high costs, insurance challenges, and limited availability of CDI therapies, impact clinical decision-making and adherence to guideline recommendations."

Journal • Infectious Disease • Transplantation

Real-world use of bezlotoxumab to prevent recurrent Clostridioides difficile infections: a single-center experience and meta-analysis. (PubMed, Therap Adv Gastroenterol) - "Our retrospective study and meta-analysis demonstrate the real-world efficacy of BEZ in reducing CDI recurrence. The higher recurrence rates in our cohort likely reflect the high-risk nature of the population, including a greater proportion of immunocompromised patients."

Journal • Real-world evidence • Retrospective data • Infectious Disease

Development of a toxin-selective immunotracer for in vivo detection of Clostridioides difficile infection by immunoPET. (PubMed, EJNMMI Radiopharm Chem) - "We successfully developed an immunoPET radiotracer targeting toxin B for detection of CDI. Its application in an animal CDI model proved its capacity to detect the source of infection with high specificity, while avoiding confusion with non-specific inflammation."

Journal • Preclinical • Infectious Disease • Inflammation

REAL-WORLD USE OF BEZLOTOXUMAB FOR PREVENTING RECURRENCE OF CLOSTRIDIOIDES DIFFICILE INFECTION IN A SPANISH PEDIATRIC POPULATION (ESPID 2025) - "Nine patients received bezlotoxumab after recurrent infections treated with vancomycin or fidaxomicin (standard or tapered), and one after a fecal microbiota transplant. Conclusions/Learning Points Bezlotoxumab shows promising results in preventing CDI recurrence in children with an adequate safety profile. These findings support its use in high-risk patients, though prospective studies are needed to define its role in pediatric CDI treatment."

Clinical • Real-world • Real-world evidence • Infectious Disease

Bezlotoxumab as Treatment for Recurrent C. Difficile Infection in Pediatric Stem Cell Transplants (ASPHO 2025) - "The use of bezlotoxumab was not associated with increased adverse events, did not impact management of graft-versus-host disease, and was safe to use in pediatric patients in the peri-transplantation period. This case series strongly suggests that bezlotoxumab is effective in treating rCDI in the pediatric SCT setting, setting the stage for a larger, multicenter study that should be done to update the standard of care for rCDI in pediatrics."

Clinical • Graft versus Host Disease • Immunology • Infectious Disease • Pediatrics • Transplantation

EFFICACY OF BEZLOTOXUMAB FOR PREVENTING RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION IN PATIENTS WITH CANCER (DDW 2025) - "Bezlotoxumab was administered in a median of 10 days (IQR 5–12.5) after symptom onset, and fidaxomicin was the most frequently used concurrent antibiotic (41.2%). Despite the high complexity of the disease and the comorbidities associated with cancer and its treatments in our selected population, bezlotoxumab demonstrated high efficacy (93.8%) in reducing CDI recurrence in a 90-day period when compared to what has been reported in the non-cancer population. Early administration of bezlotoxumab should be considered given the high effectiveness to improve the outcome."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • Pain

COMPARING EFFICACY OF BEZLOTOXUMAB, ORAL AND FECAL MICROBIOTA THERAPEUTICS, AND ANTIBIOTICS IN PREVENTING RECURRENT CLOSTRIDIUM DIFFICILE INFECTION: A NETWORK META-ANALYSIS (DDW 2025) - " We conducted a comprehensive search of electronic databases, including PubMed, Cochrane Library, and Embase, to identify Randomized Controlled Trials (RCTs) and Cohort studies from the last 10 years through October 2024 comparing the efficacy of Bezlotoxumab, Fecal Microbiota Transplant (Donor, RebyotaTM), Oral Microbiota Capsules (Donor, VowstTM, VE303TM), Vancomycin, Fidaxomicin, and Rifaximin in preventing recurrent Clostridium difficile infection...In the frequentist network meta-analysis, Actoxumab with Bezlotoxumab (RR=0.61 [0.37; 0.99]), Rebyota™ (RR=0.67 [0.45; 0.99]), VE303 (RR=0.30 [0.09; 0.97]), and Vowst™ (RR=0.29 [0.15; 0.56]) showed a statistically significant reduction in the rate of recurrent Clostridium difficile Infection (rCDI)... This review shows that Vowst™ effectively reduces recurrent Clostridium difficile infection (rCDI) rates compared to placebo and shows more consistent efficacy than other therapies. As an easy-to-use oral capsule, Vowst™ may..."

Retrospective data • Infectious Disease

Extended-pulsed Fidaxomicin Therapy for Recurrent Clostridioides difficile Infection After Standard Vancomycin and Fidaxomicin Failure: A Case Report. (PubMed, J Infect Chemother) - "Given the unavailability of bezlotoxumab (BEZ) in Japan and the limited accessibility of fecal microbiota transplantation (FMT), EPFX was selected as a salvage regimen. Importantly, the patient's medication, nutritional, and oncologic status remained stable throughout treatment, suggesting that EPFX played a pivotal role in achieving remission. EPFX may offer a viable option for patients with recurrent CDI refractory to standard therapies."

Journal • Esophageal Cancer • Gastric Cancer • Infectious Disease • Oncology • Solid Tumor • Transplantation

SAFETY AND EFFICACY OF BEZLOTOXUMAB PLUS FIDAXOMICIN IN C. DIFFICILE INFECTION TREATMENT IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTED PATIENTS (EBMT 2025) - "Amongst these 15 patients with CDI: five patients were treated with vancomycin whilst the remaining ten patients were treated with bezlotoxumab (10 mg/kg in single dose) in combination with fidaxomicin (200 mg every 12h for 11 days), the latter representing the focus of our study...70% of patients received myeloablative conditioning regimen (mainly busulfan based, 60%)... In our study, the combination of bezlotoxumab and fidaxomicin was safe and effective as treatment of CDI in HSCT patients obtaining a clinical enteritis resolution, no recurrent infections and no grade ≥3 adverse events. Further prospective studies are needed to assess the actual potential benefit of bezlotoxumab plus fidaxomicin as a first line-treatment for CDI in very high-risk patients.Table 1. Patient characteristics"

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Metabolic Disorders • Mucositis • Oncology • Septic Shock • T Cell Non-Hodgkin Lymphoma • Transplantation

Comparison of bezlotoxumab versus no-bezlotoxumab on recurrence in high-risk patients with Clostridioides difficile infection (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease