antibiotics Article Clostridioides difficile Infection among Cirrhotic Patients with Variceal Bleeding Mirela Nicoleta Voicu 1 , Florica Popescu 1 , Dan Nicolae Florescu 2 , Ion Rogoveanu 2 , Adina Turcu-Stiolica 3, * , Dan Ionut Gheonea 2 , Vlad Florin Iovanescu 2 , Sevastita Iordache 2 , Sergiu Marian Cazacu 2 and Bogdan Silviu Ungureanu 2   Citation: Voicu, M.N.; Popescu, F.; Florescu, D.N.; Rogoveanu, I.; Turcu-Stiolica, A.; Gheonea, D.I.; Iovanescu, V.F.; Iordache, S.; Cazacu, S.M.; Ungureanu, B.S. Clostridioides difficile Infection among Cirrhotic Patients with Variceal Bleeding. Antibiotics 2021, 10, 731. https://doi.org/10.3390/ antibiotics10060731 Academic Editor: Guido Granata Received: 1 May 2021 Accepted: 15 June 2021 Published: 17 June 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmacology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; nicoletamirelavoicu@gmail.com (M.N.V.); prof_floricapopescu@hotmail.com (F.P.) 2 Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; dan.florescu@umfcv.ro (D.N.F.); ion.rogoveanu@umfcv.ro (I.R.); dan.gheonea@umfcv.ro (D.I.G.); vlad.iovanescu@umfcv.ro (V.F.I.); sevastita.iordache@umfcv.ro (S.I.); sergiu.cazacu@umfcv.ro (S.M.C.); bogdan.ungureanu@umfcv.ro (B.S.U.) 3 Department of Pharmacoeconomics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania * Correspondence: adina.turcu@umfcv.ro Abstract: Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal bleeding secondary to cirrhosis requires antibiotics to prevent bacterial translocation, and thus patients become susceptible to CDI. We aimed to investigate the risk factors for CDI in cirrhotic patients with variceal bleeding following ceftriaxone and the mortality risk in this patient’s population. We retrospectively screened 367 cirrhotic patients with variceal bleeding, from which 25 patients were confirmed with CDI, from 1 January 2017 to 31 December 2019. We found MELD to be the only multivariate predictor for mortality (odds ratio, OR = 1.281, 95% confidence interval, CI: 0.098–1.643, p = 0.042). A model of four predictors (age, days of admission, Charlson index, Child–Pugh score) was generated (area under the receiver operating characteristics curve, AUC = 0.840, 95% CI: 0.758–0.921, p < 0.0001) to assess the risk of CDI exposure. Determining the probability of getting CDI for cirrhotic patients with variceal bleeding could be a tool for doctors in taking decisions, which could be integrated in sustainable public health programs. Keywords: Clostridioides difficile; risk factors; Charlson comorbidity index; Child–Pugh score 1. Introduction Clostridioides difficile infection (CDI) represents the leading cause of nosocomial infec- tion and is associated with high morbidity and mortality as well as increased healthcare costs [1]. A European multicentre study involving 482 hospitals showed a rate of seven cases per 10,000 patients and also revealed a suboptimal laboratory diagnosis in the eastern European countries [2]. While it seems that CDI is shifting towards community spreading, there are still many hospital-acquired cases, especially in patients with comorbidities and if antibiotics are used. Chronic disease, older age, immunosuppressive and oncologic medication are consid- ered risk factors for patients acquiring hospital CDI [3]. Additionally, the increased use of proton pump inhibitors (PPI) [4] and nonsteroidal anti-inflammatory drugs (NSAID) [5] has been associated with an increase in CDI. Even though any antibiotic may be incrim- inated for inducing hospital-based infection by disrupting the gut barrier, clindamycin, cephalosporins and fluoroquinolones have been frequently linked to CDI [6]. Liver cir- rhosis is the 13th cause of death worldwide, even though the viral aetiology seems to be Antibiotics 2021, 10, 731. https://doi.org/10.3390/antibiotics10060731 https://www.mdpi.com/journal/antibiotics