Orenstein, Robert

Background: Fecal microbiota, live-jslm (RBL) is approved in the United States and Canada for prevention of recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. Objectives: Provide an updated integrated safety analysis, incorporating final safety data from Punch CD3-OLS. Design: Safety data were combined from five RBL trials: three phase II and two phase III trials. Methods: Adult participants had documented rCDI and completed SOC therapy before receiving one or two doses of RBL or placebo, rectally administered as one treatment course. Treatment-emergent adverse events (TEAEs) were recorded for ⩽6 months. Results: TEAEs were reported in 70.9% (845/1192) of RBL recipients; most TEAEs were mild to moderate and gastrointestinal in nature. Most serious TEAEs were related to preexisting conditions or CDI. There was no clustering of serious TEAEs. Most TEAEs leading to death were related to preexisting conditions. Conclusion: Overall, data demonstrate RBL has a favorable 6-month safety profile. Trial registration: ClinicalTrials.gov: NCT01925417; NCT02299570; NCT02589847; NCT03244644; NCT03931941.

Abstract Background Bezlotoxumab is a monoclonal antibody infusion approved to prevent recurrence of Clostridioides difficile infection (CDI). The objective of this study was to explore outcomes associated with bezlotoxumab use at three academic medical centers. Methods A retrospective cohort study was conducted with 180 patients who received bezlotoxumab from May 2018 through November 2023. The primary outcome was recurrence of CDI within 12 weeks of receipt of bezlotoxumab. The study also sought to evaluate risk factors for CDI recurrence in patients who received bezlotoxumab. Results Of the 180 patients who received bezlotoxumab at our institution, 165 were included in the study. Fifteen patients were excluded because they did not improve with standard of care CDI treatment. In the study cohort, 45% were immunosuppressed (n=75), 17% had a solid organ transplant (n=28), and 16% had a history of inflammatory bowel disease (n=27). Ninety-five percent of patients received bezlotoxumab as an outpatient (n=156). Recurrence of CDI within 12 weeks occurred in 16% of patients. Duration from diagnosis of CDI to bezlotoxumab infusion (p=0.022) and having greater than two prior CDI episodes (p=0.032) were statistically significant predictors for CDI recurrence within 30 days. Conclusion Our study demonstrated similar CDI recurrence rates for patients who received bezlotoxumab in a real-world setting compared to previous clinical trials. Patients with CDI may benefit from receiving bezlotoxumab earlier in the course of illness and prior to developing multiple recurrences. Disclosures Robert Orenstein, DO, FACP, Ferring: Advisor/Consultant|Ferring: Honoraria

Abstract Background Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD. Methods Participants with IBD (ulcerative colitis [UC], Crohn’s disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months. Results Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively). Conclusions The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.

Background: Culture-negative vertebral osteomyelitis presents a significant diagnostic challenge. Neisseria sicca (N. sicca) is a typically benign commensal organism of the upper respiratory tract that rarely causes invasive infections, warranting cautious interpretation if isolated in a single positive culture. This case study details a 62-year-old male diagnosed with vertebral osteomyelitis caused by N. sicca, examining diagnostic challenges, treatment, and outcomes. Methods: We conducted a comprehensive search on MEDLINE using the keywords “Neisseria sicca”, “osteomyelitis”, and “diskitis”. An additional search excluding N. gonorrhea and N. meningitidis was also performed, revealing a total of four cases of N. sicca osteomyelitis in the literature. Results: A 62-year-old male with a history of hypertension, type 2 diabetes, atrial fibrillation, and previous L5-S1 spinal fusion presented with fever and back pain in May 2023. Initial imaging revealed T8-T9 vertebral osteomyelitis. Despite a six-week course of IV daptomycin, his symptoms worsened, prompting further evaluation. A CT-guided biopsy with comprehensive testing, including histopathology and microbial cultures, initially identified N. sicca. Due to its rarity, additional biopsies were conducted, confirming the infection. IV ceftriaxone was initiated, leading to significant pain improvement, and a subsequent MRI showed near resolution. The patient transitioned to oral cefuroxime, with follow-up confirming complete infection resolution by December 2023. Conclusions: This case underscores the importance of a structured diagnostic approach in culture-negative vertebral osteomyelitis to differentiate between commensal contamination and true infection. Repeated positive cultures of N. sicca from a sterile site confirmed its role as the causative agent. Early identification and targeted antibiotic therapy are critical to improving outcomes in rare cases of N. sicca vertebral osteomyelitis.

Abstract Deep sternal wound infection is a rare complication of cardiac surgery that is typically caused by skin resident flora, such as species of Staphylococcus and Streptococcus. Infections caused by fungi are less common and are generally caused by Candida species. Regardless of etiology, these infections are associated with significant morbidity and mortality. We present a case of postoperative mediastinitis that occurred following a 5-vessel coronary artery bypass graft and was caused by a filamentous fungus of the Rhizopus genus. The patient was treated with serial debridement, liposomal amphotericin B, and isavuconazonium and was discharged from the hospital in stable condition. Fungal mediastinitis is a rare entity, and clinicians must maintain a high level of suspicion to make the diagnosis. A fungal cause of postoperative mediastinitis should be considered in patients with negative bacterial cultures, uncontrolled diabetes, or current immunosuppression or those who present weeks after surgery with a subacute onset of symptoms.

Abstract Mpox, caused by infection with Monkeypox virus, usually presents as a mild, self-limited illness in immunocompetent persons that resolves within 2–4 weeks. Serious complications have been reported when mpox lesions involve vulnerable anatomic sites, such as the eye, and in those with substantial immunosuppression. We describe a patient with advanced human immunodeficiency virus infection and sustained viral shedding of mpox with ocular involvement, which resulted in vision loss.