{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:06:07Z","timestamp":1793120767687,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy"},{"id":[{"id":"https:\/\/ror.org\/0391j1294","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Clostridioides difficile infection (CDI) is an increasingly recognised nosocomial complication in patients hospitalised with coronavirus disease 2019 (COVID-19), driven by broad-spectrum antibiotic exposure, corticosteroid use, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related intestinal dysbiosis. The contribution of underlying cardiovascular comorbidities, particularly heart failure, to CDI susceptibility in hospitalised COVID-19 patients remains insufficiently characterised. We aimed to evaluate the prevalence, risk factors, and clinical impact of CDI in hospitalised COVID-19 patients at a tertiary Romanian infectious diseases centre, with a specific focus on cardiovascular disease and modifiable antimicrobial-prescribing factors. Methods: This single-centre retrospective observational cohort study enrolled 395 consecutive adult patients hospitalised with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) at the \u201cVictor Babe\u0219\u201d Clinical Hospital for Infectious Diseases and Pneumophthisiology, Timi\u0219oara, Romania, between 1 March 2020 and 31 December 2024. Patients were stratified into a CDI group (n = 24) and a non-CDI group (n = 371) on the basis of hospital-onset CDI. Demographic, clinical, laboratory, therapeutic, and outcome variables were extracted from electronic medical records. Continuous variables were compared using Student\u2019s independent-samples t-test, categorical variables using Fisher\u2019s exact test; odds ratios (ORs) with exact 95% confidence intervals (CIs) were computed for all binary comparisons, and a parsimonious multivariable logistic regression was used to adjust the antibiotic-exposure effect for age. Temporal relationships between CDI onset and sepsis documentation were also analysed. A two-sided p-value &lt; 0.05 was considered statistically significant. Results: CDI was identified in 24 patients (prevalence 6.1%). The CDI and non-CDI groups were comparable in age (71.1 \u00b1 10.2 vs. 71.7 \u00b1 11.4 years; p = 0.817), sex distribution (50.0% vs. 45.8% female; p = 0.833), and vaccination status (p = 0.383). Heart failure prevalence did not differ between groups (29.2% vs. 26.7%; OR 1.13, 95% CI 0.46\u20132.81; p = 0.813). Any antibiotic therapy was strongly associated with CDI (95.8% vs. 70.6%; OR 9.57, 95% CI 1.28\u201371.74; p = 0.004), as was longer duration of antibiotic therapy (8.1 \u00b1 2.2 vs. 5.2 \u00b1 3.7 days; p &lt; 0.001). In the multivariable model, each additional day of antibiotic therapy was independently associated with a 13.6% increase in the odds of CDI (adjusted OR 1.14 per day, 95% CI 1.03\u20131.26; p = 0.013) after adjustment for age. Piperacillin\/tazobactam accounted for 65.2% (15\/23) of the recorded pre-CDI broad-spectrum antibiotic regimens among antibiotic-exposed CDI patients. Documented sepsis was substantially more frequent in CDI patients (95.8% vs. 15.4%; p &lt; 0.001) and length of hospitalisation was prolonged (15.6 \u00b1 8.2 vs. 12.0 \u00b1 8.1 days; p = 0.038). In-hospital mortality did not differ significantly (4.2% vs. 7.5%; p = 1.000). Conclusions: Hospital-onset CDI complicated 6.1% of hospitalised COVID-19 admissions and was independently associated with the cumulative duration of antibiotic therapy. Heart failure was not significantly associated with CDI in this cohort; however, given the limited number of CDI events, this should be interpreted as absence of evidence rather than evidence of absence. CDI was also associated with prolonged hospitalisation and high co-occurrence of documented sepsis, although causality cannot be inferred from the retrospective design. These findings support strengthened antibiotic stewardship and targeted CDI surveillance in COVID-19 inpatient wards.<\/jats:p>","DOI":"10.3390\/jcm15145488","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:34:44Z","timestamp":1783996484000},"page":"5488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clostridioides difficile Infection in Hospitalised COVID-19 Patients: Antibiotic Exposure, Cardiovascular Comorbidities, and Clinical Outcomes in a Romanian Tertiary Infectious Diseases Centre"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2467-9091","authenticated-orcid":false,"given":"Cristiana Georgeta","family":"Bujor","sequence":"first","affiliation":[{"name":"Department IV\u2014Biochemistry and Pharmacology, Faculty of Medicine, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Dinuti","sequence":"additional","affiliation":[{"name":"Department IV\u2014Biochemistry and Pharmacology, Faculty of Medicine, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Sfrijan","sequence":"additional","affiliation":[{"name":"Department IV\u2014Biochemistry and Pharmacology, Faculty of Medicine, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-9010","authenticated-orcid":false,"given":"Alina Ramona","family":"Buzatu","sequence":"additional","affiliation":[{"name":"Department IV\u2014Biochemistry and Pharmacology, Faculty of Medicine, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa1408913","article-title":"Burden of Clostridium difficile infection in the United States","volume":"372","author":"Lessa","year":"2015","journal-title":"N. 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