{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T10:21:12Z","timestamp":1770546072544,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["UIP-2019-04-7194"],"award-info":[{"award-number":["UIP-2019-04-7194"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Recurrent Clostridioides difficile infections (rCDI) have a substantial impact on healthcare systems, with limited and often expensive therapeutic options. Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the adult population and is associated with metabolic syndrome, changes in gut microbiome and bile acids biosynthesis, all possibly related with rCDI. The aim of this study was to determine whether NAFLD is a risk factor associated with rCDI. A retrospective cohort study included patients \u2265 60 years hospitalized with CDI. The cohort was divided into two groups: those who were and were not readmitted with CDI within 3 months of discharge. Of the 329 patients included, 107 patients (32.5%) experienced rCDI. Patients with rCDI were older, had higher Charlson Age\u2013Comorbidity Index (CACI) and were more frequently hospitalized within 3 months. Except for chronic kidney disease and NAFLD, which were more frequent in the rCDI group, there were no differences in other comorbidities, antibiotic classes used and duration of antimicrobial therapy. Multivariable Cox regression analysis showed that age &gt;75 years, NAFLD, CACI &gt;6, chronic kidney disease, statins and immobility were associated with rCDI. In conclusion, our study identified NAFLD as a possible new host-related risk factor associated with rCDI.<\/jats:p>","DOI":"10.3390\/antibiotics10070780","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nonalcoholic Fatty Liver Disease\u2014A Novel Risk Factor for Recurrent Clostridioides difficile Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Lara","family":"\u0160amadan","sequence":"first","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Jeli\u010di\u0107","sequence":"additional","affiliation":[{"name":"University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Vince","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5784-1343","authenticated-orcid":false,"given":"Neven","family":"Papi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care-associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Crobach, M.J.T., Vernon, J.J., Loo, V.G., Kong, L.Y., Pechine, S., Wilcox, M.H., and Kuijper, E.J. (2018). Understanding Clostridium difficile Colonization. Clin. Microbiol. Rev., 31.","DOI":"10.1128\/CMR.00021-17"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa0910812","article-title":"Fidaxomicin versus vancomycin for Clostridium difficile infection","volume":"364","author":"Louie","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1086\/430315","article-title":"Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada","volume":"40","author":"Pepin","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5009\/gnl18071","article-title":"Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention","volume":"13","author":"Song","year":"2019","journal-title":"Gut Liver"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1017\/ice.2014.88","article-title":"Risk factors for recurrent Clostridium difficile infection: A systematic review and meta-analysis","volume":"36","author":"Deshpande","year":"2015","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jmii.2013.08.003","article-title":"Risk factors for Clostridium difficile-associated diarrhea among hospitalized adults with fecal toxigenic C. difficile colonization","volume":"48","author":"Lin","year":"2015","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ajic.2010.08.017","article-title":"Diabetes mellitus as a risk factor for recurrence of Clostridium difficile infection in the acute care hospital setting","volume":"39","author":"Shakov","year":"2011","journal-title":"Am. J. Infect. Control"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/cid\/cit280","article-title":"Obesity as a risk factor for Clostridium difficile infection","volume":"57","author":"Bishara","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s10096-019-03539-6","article-title":"Clostridium difficile infection: Review","volume":"38","author":"Czepiel","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"European Association for the Study of The Liver, European Association for the Study of Diabetes, and European Association for the Study of Obesity (EASO) (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-physiol-021115-105331","article-title":"Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease","volume":"78","author":"Haas","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/apt.15314","article-title":"Review article: Emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications","volume":"50","author":"Jayakumar","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1099\/0022-1317-51-5-448","article-title":"Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection","volume":"51","author":"Hopkins","year":"2002","journal-title":"J. Med. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10096-019-03759-w","article-title":"Nonalcoholic fatty liver disease as a risk factor for Clostridioides difficile infection","volume":"39","author":"Papic","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/qjmed\/hcz283","article-title":"Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea","volume":"113","author":"Nseir","year":"2020","journal-title":"QJM"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.cmi.2014.08.017","article-title":"Recurrent Clostridium difficile infection is associated with increased mortality","volume":"21","author":"Olsen","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.anaerobe.2019.04.004","article-title":"High delayed mortality after the first episode of Clostridium difficile infection","volume":"57","author":"Cozar","year":"2019","journal-title":"Anaerobe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5556354","DOI":"10.1155\/2021\/5556354","article-title":"NAFLD and Infection, a Nuanced Relationship","volume":"2021","author":"Adenote","year":"2021","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_21","first-page":"412","article-title":"Recurrent Urinary Tract Infection: Time to Recommend Weight Loss?","volume":"21","author":"Mari","year":"2019","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.dld.2015.10.004","article-title":"The association between primary bacteremia of presumed gastrointestinal origin and nonalcoholic fatty liver disease","volume":"48","author":"Nseir","year":"2016","journal-title":"Dig. Liver Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1007\/s10620-011-1736-5","article-title":"Fatty liver is associated with recurrent bacterial infections independent of metabolic syndrome","volume":"56","author":"Nseir","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/qjmed\/hcy227","article-title":"Non-alcoholic fatty liver disease and 30-day all-cause mortality in adult patients with community-acquired pneumonia","volume":"112","author":"Nseir","year":"2019","journal-title":"QJM"},{"key":"ref_25","first-page":"124","article-title":"Non-Alcoholic Fatty Liver Disease is Associated with an Increased Mortality in Adult Patients with Group B Streptococcus Invasive Disease","volume":"40","author":"Gjurasin","year":"2020","journal-title":"Croat. J. Infect."},{"key":"ref_26","first-page":"806248","article-title":"Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption","volume":"2015","author":"Mitra","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.cmet.2019.08.002","article-title":"Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease","volume":"30","author":"Loomba","year":"2019","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fimmu.2019.00082","article-title":"The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity","volume":"10","author":"Weyler","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.orcp.2013.12.007","article-title":"Is obesity a risk factor for Clostridium difficile infection?","volume":"9","author":"Punni","year":"2015","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1007\/s10620-018-5108-2","article-title":"Does Obesity Influence the Risk of Clostridium difficile Infection Among Patients with Ulcerative Colitis?","volume":"63","author":"Chandradas","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s10620-019-05888-w","article-title":"Obesity Is Associated with Decreased Risk of Clostridium difficile Infection in Hospitalized Patients with Pouchitis","volume":"65","author":"Gosai","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13251","DOI":"10.1111\/ijcp.13251","article-title":"Incidence and in-hospital outcomes of Clostridium difficile infection among type 2 diabetes patients in Spain","volume":"72","year":"2018","journal-title":"Int. J. Clin. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s10096-011-1522-5","article-title":"Hospital-acquired Clostridium difficile infection: Determinants for severe disease","volume":"31","author":"Wenisch","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature12198","article-title":"Gut metagenome in European women with normal, impaired and diabetic glucose control","volume":"498","author":"Karlsson","year":"2013","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s10096-015-2348-3","article-title":"Predicting Clostridium difficile infection in diabetic patients and the effect of metformin therapy: A retrospective, case-control study","volume":"34","author":"Fishman","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, S., and Yadav, H. (2021). Metformin reduces Clostridium difficile infection. FASEB J., 35.","DOI":"10.1096\/fasebj.2021.35.S1.03618"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1440-1797.2009.01274.x","article-title":"Chronic kidney disease as a risk factor for Clostridium difficile infection","volume":"15","author":"Eddi","year":"2010","journal-title":"Nephrology"},{"key":"ref_38","first-page":"681","article-title":"Clostridium difficile-associated diarrhea and chronic renal insufficiency","volume":"95","author":"Yousuf","year":"2002","journal-title":"South. Med. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3904\/kjim.2016.31.1.125","article-title":"Advanced chronic kidney disease: A strong risk factor for Clostridium difficile infection","volume":"31","author":"Kim","year":"2016","journal-title":"Korean J. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.mayocp.2012.05.025","article-title":"Clostridium difficile infection in patients with chronic kidney disease","volume":"87","author":"Keddis","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/clc.22577","article-title":"Prevalence and Factors Associated With Statin Use Among a Nationally Representative Sample of US Adults: National Health and Nutrition Examination Survey, 2011\u20132012","volume":"39","author":"Adedinsewo","year":"2016","journal-title":"Clin. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1007\/s40265-013-0126-z","article-title":"Pharmacology of the new P2Y12 receptor inhibitors: Insights on pharmacokinetic and pharmacodynamic properties","volume":"73","author":"Ferri","year":"2013","journal-title":"Drugs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4103\/ijmr.IJMR_1973_17","article-title":"Statins & risk of Clostridium difficile infection: A meta-analysis","volume":"150","author":"Wijarnpreecha","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"G488","DOI":"10.1152\/ajpgi.00149.2016","article-title":"The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles","volume":"312","author":"Nolan","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41586-020-2269-x","article-title":"Statin therapy is associated with lower prevalence of gut microbiota dysbiosis","volume":"581","author":"Falony","year":"2020","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e00601","DOI":"10.1002\/prp2.601","article-title":"Gut bacterial microbiome composition and statin intake-A systematic review","volume":"8","author":"Dias","year":"2020","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_47","first-page":"477","article-title":"Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide","volume":"34","year":"2013","journal-title":"Saudi Med. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/00004836-200508000-00012","article-title":"Hepatic MRI for fat quantitation: Its relationship to fat morphology, diagnosis, and ultrasound","volume":"39","author":"Fishbein","year":"2005","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1055\/s-2001-12930","article-title":"Imaging of hepatic steatosis","volume":"21","author":"Siegelman","year":"2001","journal-title":"Semin. Liver Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/cid\/cis430","article-title":"Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain","volume":"55","author":"Petrella","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/cix1085","article-title":"Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)","volume":"66","author":"McDonald","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/1469-0691.12418","article-title":"European Society of Clinical Microbiology and Infectious Diseases: Update of the treatment guidance document for Clostridium difficile infection","volume":"20","author":"Debast","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.cmi.2017.12.022","article-title":"Update of treatment algorithms for Clostridium difficile infection","volume":"24","author":"Ooijevaar","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Miller, M.A., Louie, T., Mullane, K., Weiss, K., Lentnek, A., Golan, Y., Kean, Y., and Sears, P. (2013). Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-148"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/23744235.2018.1425551","article-title":"Efficacy of oral vancomycin in primary prevention of Clostridium Difficile infection in elderly patients treated with systemic antibiotic therapy","volume":"50","author":"Papic","year":"2018","journal-title":"Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/cid\/ciw401","article-title":"Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents","volume":"63","author":"Bryant","year":"2016","journal-title":"Clin. Infect. Dis"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/7\/780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:25:02Z","timestamp":1760163902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/7\/780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,27]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["antibiotics10070780"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10070780","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,27]]}}}