{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:11:58Z","timestamp":1774973518952,"version":"3.50.1"},"reference-count":13,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background: Bezlotoxumab is used to prevent recurrent Clostridioides difficile infection. Although well tolerated, heart failure (HF) exacerbations have been reported as adverse events in clinical trials. This study evaluates the incidence and predictors of HF exacerbation following bezlotoxumab. Methods: We used the TriNetX research database to identify U.S. adults who received bezlotoxumab and stratified them into three groups based on HF history: no HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). The 90-day cumulative incidence of HF events and mortality were assessed. Cox proportional hazard models identified predictors of HF events. Results: Among 2515 patients, 89% had no HF history, 4% had HFpEF, and 7% had HFrEF. The 90-day HF event rates were 1%, 29%, and 52% for the no HF, HFpEF, and HFrEF groups, respectively (p &lt; 0.001). The 90-day all-cause mortality was 0.9%. Corresponding 90-day all-cause mortality rates were 0.04%, 4%, and 11%, respectively (p &lt; 0.001). Independent positive predictors of HF events included HFrEF (aHR 19.400), HFpEF (adjusted hazard ratio [aHR] 8.632), heart transplant (aHR 7.485), hyperlipidemia (aHR 3.184), valvular heart disease (aHR 2.267), chronic kidney disease stage \u2265 3 (aHR 1.715), and ischemic heart disease (aHR 1.987). Protective factors included non-cardiac solid organ transplant (aHR 0.333). Conclusions: Bezlotoxumab appears safe in patients without HF history but is associated with a significantly increased risk of HF exacerbation in those with pre-existing HF, especially HFrEF.<\/jats:p>","DOI":"10.3390\/idr18020028","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heart Failure Incidence and Risk Factors in U.S. Adults Receiving Bezlotoxumab: A Large Database Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-3435","authenticated-orcid":false,"given":"Chia-Yu","family":"Chiu","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-0195","authenticated-orcid":false,"given":"Daniel B.","family":"Chastain","sequence":"additional","affiliation":[{"name":"Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Albany, GA 31701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-8929","authenticated-orcid":false,"given":"Joseph","family":"Sassine","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-8652","authenticated-orcid":false,"given":"Andr\u00e9s F.","family":"Henao-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","unstructured":"ZINPLAVA\u2122 (Bezlotoxumab) (2025, August 01). Package Insert, Available online: https:\/\/www.Accessdata.Fda.Gov\/Drugsatfda_docs\/Label\/2023\/761046s012lbl.Pdf."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Granata, G., Schiavone, F., and Pipitone, G. (2022). Bezlotoxumab in Patients with a Primary Clostridioides Difficile Infection: A Literature Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11111495"},{"key":"ref_3","unstructured":"TriNetX (2026, January 01). Available online: https:\/\/trinetx.com\/about-trinetx\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e0192424","DOI":"10.1128\/aac.01924-24","article-title":"Incidence of Fidaxomicin Allergy in Patients with Macrolide Allergies: A Large Database Analysis","volume":"69","author":"Chiu","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jaip.2024.11.010","article-title":"Incidence of Anaphylaxis in Patients with Alpha-Gal Syndrome Receiving Gelatin-Containing Vaccines: A Large Database Analysis","volume":"13","author":"Chiu","year":"2024","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1007\/s10096-019-03630-y","article-title":"Real-World Efficacy of Bezlotoxumab for Prevention of Recurrent Clostridium Difficile Infection: A Retrospective Study of 46 Patients in Five University Hospitals in Finland","volume":"38","author":"Oksi","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Escudero-S\u00e1nchez, R., Ru\u00edz-Ruizg\u00f3mez, M., Fern\u00e1ndez-Fradejas, J., Garc\u00eda Fern\u00e1ndez, S., Olmedo Samperio, M., Cano Yuste, A., Valencia Alijo, A., D\u00edaz-Poll\u00e1n, B., Rodr\u00edguez Hern\u00e1ndez, M.J., and Merino De Lucas, E. (2020). Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides Difficile Infection. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010002"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ofaa097","DOI":"10.1093\/ofid\/ofaa097","article-title":"Real-World Experience of Bezlotoxumab for Prevention of Clostridioides Difficile Infection: A Retrospective Multicenter Cohort Study","volume":"7","author":"Hengel","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/cid\/ciab674","article-title":"Real-World Comparison of Bezlotoxumab to Standard of Care Therapy for Prevention of Recurrent Clostridioides Difficile Infection in Patients at High Risk for Recurrence","volume":"74","author":"Johnson","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"ofac492.1633","DOI":"10.1093\/ofid\/ofac492.1633","article-title":"Real-World Experience of Administration of Bezlotoxumab in an Outpatient Infusion Center upon Discharge in Recurrent Clostridioides Difficile Patients","volume":"9","author":"Bradley","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S-698","DOI":"10.1016\/S0016-5085(23)02620-3","article-title":"Cardiac Events in Heart Failure Patients Treated with Bezlotoxumab for Recurrent C. Difficile Prevention: A Multicenter Study","volume":"164","author":"Chaar","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ijcard.2020.08.033","article-title":"Cardiotoxic Mechanisms of Cancer Immunotherapy\u2014A Systematic Review","volume":"323","author":"Lobenwein","year":"2021","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez-Bail\u00f3n, M., Jim\u00e9nez-Garc\u00eda, R., Hern\u00e1ndez-Barrera, V., de Miguel-D\u00edez, J., de Miguel-Yanes, J.M., Mu\u00f1oz-Rivas, N., Lorenzo-Villalba, N., Carabantes-Alarcon, D., Zamorano-Le\u00f3n, J.J., and Astasio-Arbiza, P. (2020). Heart Failure Is a Risk Factor for Suffering and Dying of Clostridium Difficile Infection. Results of a 15-Year Nationwide Study in Spain. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030614"}],"container-title":["Infectious Disease Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2036-7449\/18\/2\/28\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T14:05:06Z","timestamp":1774965906000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2036-7449\/18\/2\/28"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":13,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["idr18020028"],"URL":"https:\/\/doi.org\/10.3390\/idr18020028","relation":{},"ISSN":["2036-7449"],"issn-type":[{"value":"2036-7449","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]}}}