{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T08:07:27Z","timestamp":1784966847624,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T00:00:00Z","timestamp":1577923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Extraintestinal manifestations of Clostridioides difficile infections (CDIs) are very uncommon, and according to the literature, poor outcomes and a high mortality have been observed among affected individuals. The objective of this study was to investigate the incidence rate of extraintestinal infections caused by C. difficile (ECD) in a tertiary-care university hospital in Hungary. During a 10-year study period, the microbiology laboratory isolated 4129 individual strains of C. difficile; among these, the majority were either from diarrheal fecal samples or from colonic material and only n = 24 (0.58%) were from extraintestinal sources. The 24 extraintestinal C. difficile isolates were recovered from 22 patients (female-to-male ratio: 1, average age: 55.4 years). The isolates in n = 8 patients were obtained from abdominal infections, e.g., appendicitis, rectal abscess or Crohn\u2019s disease. These extraintestinal cases occurred without concomitant diarrhea. In all, but two cases C. difficile was obtained as a part of a polymicrobial flora. Our isolates were frequently toxigenic and mostly belonged to PCR ribotype 027. Resistance to metronidazole, vancomycin, clindamycin and rifampin were 0%, 0%, 20.5% and 9.7%, respectively. The increasing amount of reports of C. difficile extraintestinal infections should be noted, as these infections are characterized by a poor outcome and high mortality rate.<\/jats:p>","DOI":"10.3390\/antibiotics9010016","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Extraintestinal Clostridioides difficile Infections: Epidemiology in a University Hospital in Hungary and Review of the Literature"],"prefix":"10.3390","volume":"9","author":[{"given":"Edit","family":"Urb\u00e1n","sequence":"first","affiliation":[{"name":"Department of Public Health, Faculty of Medicine, University of Szeged, D\u00f3m t\u00e9r 10., 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Terhes","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis utca 6., 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-0365","authenticated-orcid":false,"given":"M\u00e1ri\u00f3","family":"Gajd\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6., 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1099\/00222615-45-2-133","article-title":"The distribution of Clostridium difficile in the environment of South Wales","volume":"45","author":"Brazier","year":"1996","journal-title":"J. Med. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nrmicro.2016.108","article-title":"Clostridium difficile colitis: Pathogenesis and host defence","volume":"14","author":"Abt","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1128\/CMR.00082-09","article-title":"The changing epidemiology of Clostridium difficile infections","volume":"23","author":"Freeman","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1503\/cmaj.1041033","article-title":"Quebec strikes committee on Clostridium difficile","volume":"171","author":"Eggertson","year":"2004","journal-title":"CMAJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1469-0691.2006.01580.x","article-title":"Emergence of Clostridium difficile-associated disease in North America and Europe","volume":"12","author":"Kuijper","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1128\/jb.84.1.65-67.1962","article-title":"Occurrence of Clostridium difficile in infections of man","volume":"84","author":"Smith","year":"1962","journal-title":"J. Bacteriol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/23744235.2019.1648857","article-title":"The relevance of anaerobic bacteria in brain abscesses: A ten-year retrospective analysis (2008\u20132017)","volume":"51","year":"2019","journal-title":"Infect. Dis. (Lond.)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.anaerobe.2009.10.004","article-title":"Rare extraintestinal infection caused by toxin-producing Clostridium difficile","volume":"16","author":"Terhes","year":"2010","journal-title":"Anaerobe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/00005792-200103000-00002","article-title":"Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature","volume":"80","author":"Jacobs","year":"2001","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s10067-007-0710-2","article-title":"Clostridium difficile: An under-recognized cause of reactive arthritis?","volume":"27","author":"Birnbaum","year":"2008","journal-title":"Clin. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1297-319X(03)00056-3","article-title":"Clostridium difficile-associated reactive arthritis in two children","volume":"71","author":"Pron","year":"2004","journal-title":"Jt. Bone Spine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jbspin.2010.01.007","article-title":"Reactive arthritis due to Clostridium difficile","volume":"77","author":"Prati","year":"2010","journal-title":"Jt. Bone Spine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/BF01690732","article-title":"Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile","volume":"14","author":"Pron","year":"1995","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S0163-4453(99)90110-X","article-title":"Clostridium difficile infection of a prosthetic joint presenting 12 months after antibiotic-associated diarrhoea","volume":"39","author":"McCarthy","year":"1999","journal-title":"J. Infect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1136\/bmj.284.6324.1217","article-title":"Chronic osteomyelitis due to Clostridium difficile","volume":"284","author":"Riley","year":"1982","journal-title":"Br. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/00007632-198801000-00027","article-title":"Vertebral osteomyelitis caused by Clostridium difficile. A case report and review of the literature","volume":"13","author":"Incavo","year":"1988","journal-title":"Spine"},{"key":"ref_17","first-page":"389","article-title":"Splenic abscess due to Clostridium difficile and Pseudomonas paucimobilis","volume":"82","author":"Studemeister","year":"1987","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/infdis\/147.6.1105","article-title":"Splenic abscess due to Clostridium difficile","volume":"147","author":"Saginur","year":"1983","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1128\/JCM.41.1.509-511.2003","article-title":"Clostridium difficile brain empyema after prolonged intestinal carriage","volume":"41","author":"Gravisse","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s15010-011-0115-7","article-title":"Two case reports of Clostridium difficile bacteremia, one with the epidemic NAP-1 strain","volume":"39","author":"Hemminger","year":"2011","journal-title":"Infection"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.anaerobe.2007.04.001","article-title":"Molecular characterization and antimicrobial susceptibilities of extra-intestinal Clostridium difficile isolates","volume":"13","author":"Zheng","year":"2007","journal-title":"Anaerobe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1086\/313825","article-title":"Rapidly progressive necrotizing fasciitis and gangrene due to Clostridium difficile: Case report","volume":"30","author":"Bhargava","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","first-page":"2013","article-title":"Pseudomembranous colitis due to Clostridium difficile as a cause of perineal necrotising fasciitis","volume":"22","author":"Duburcq","year":"2013","journal-title":"BMJ Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1136\/jcp.49.2.172","article-title":"Nosocomial empyema caused by Clostridium difficile","volume":"49","author":"Simpson","year":"1996","journal-title":"J. Clin. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5083535","DOI":"10.1155\/2017\/5083535","article-title":"Acute Appendicitis: An Extracolonic Manifestation of Clostridium difficile Colitis","volume":"2017","author":"Ridha","year":"2017","journal-title":"Case Rep. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S256","DOI":"10.1093\/clinids\/16.Supplement_4.S256","article-title":"Bacteriology of anaerobic pleuropulmonary infections: Preliminary report","volume":"16","author":"Marina","year":"1993","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","first-page":"2017","article-title":"Invading beyond bounds: Extraintestinal Clostridium difficile infection leading to pancreatic and liver abscesses","volume":"8","author":"Roy","year":"2017","journal-title":"BMJ Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.anaerobe.2016.12.013","article-title":"Fatal community-acquired ribotype 002 Clostridium difficile bacteremia","volume":"44","author":"Dauby","year":"2017","journal-title":"Anaerobe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/003655401750064112","article-title":"Liver abscess caused by Clostridium difficile","volume":"33","author":"Sakurai","year":"2001","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.anaerobe.2016.09.007","article-title":"Clostridium difficile: A rare cause of pyogenic liver abscess","volume":"42","author":"Ulger","year":"2016","journal-title":"Anaerobe"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e7969","DOI":"10.1097\/MD.0000000000007969","article-title":"Recurrent bacteremia and liver abscess caused by Clostridium difficile. A case report","volume":"96","author":"Hiroshi","year":"2017","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1097\/00003246-199506000-00024","article-title":"Clostridium difficile causing sepsis and an acute abdomen in critically ill patients","volume":"23","author":"Chatila","year":"1995","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1007\/BF02044130","article-title":"Clostridium difficile infection as a cause of severe sepsis","volume":"22","author":"Lowenkron","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijid.2009.01.014","article-title":"Bacteremia due to Clostridium difficile-review of the literature","volume":"13","author":"Libby","year":"2009","journal-title":"Int. J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.3201\/eid1608.100064","article-title":"Clostridium difficile bacteremia, Taiwan","volume":"16","author":"Lee","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"943","DOI":"10.4065\/73.10.943","article-title":"Extraintestinal Clostridium difficile: 10 years\u2019 experience at a tertiary-care hospital","volume":"73","author":"Wolf","year":"1998","journal-title":"Mayo Clin. Proc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1469-0691.2001.00313.x","article-title":"Extraintestinal infections caused by Clostridium difficile","volume":"7","author":"Hernangomez","year":"2001","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0002-9343(03)00184-0","article-title":"Recurrent extraintestinal Clostridum difficile infection","volume":"9","author":"Bedimo","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/clinids\/20.1.160","article-title":"Elevated serum antibody response to toxin a following splenic abscess due to Clostridium difficile","volume":"20","author":"Stieglbauer","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1093\/cid\/cit392","article-title":"Extraintestinal Clostridium difficile infections","volume":"57","author":"Mattila","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.mayocp.2014.07.012","article-title":"Extraintestinal Clostridium difficile infections: A single-center experience","volume":"89","author":"Gupta","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1152\/ajpgi.00380.2011","article-title":"Colonic microbiome is altered in alcoholism","volume":"302","author":"Mutlu","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.anaerobe.2009.01.010","article-title":"Assessment of changes in the epidemiology of Clostridium difficile isolated from diarrheal patients in Hungary","volume":"15","author":"Terhes","year":"2009","journal-title":"Anaerobe"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1128\/JCM.42.9.4316-4318.2004","article-title":"Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A, and toxin B gene-positive isolates in Hungary","volume":"42","author":"Terhes","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.anaerobe.2014.08.002","article-title":"Investigation of the MICs of fidaxomicin and other antibiotics against Hungarian Clostridium difficile isolates","volume":"31","author":"Eitel","year":"2015","journal-title":"Anaerobe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.anaerobe.2014.08.005","article-title":"In vitro antibiotic susceptibility profile of Clostridium difficile excluding PCR ribotype 027 outbreak strain in Hungary","volume":"30","author":"Terhes","year":"2014","journal-title":"Anaerobe"},{"key":"ref_47","unstructured":"(2019, December 07). Hospital Bed Count and Patient Turnover Report 2017, Available online: http:\/\/www.neak.gov.hu\/felso_menu\/szakmai_oldalak\/publikus_forgalmi_adatok\/gyogyito_megelozo_forgalmi_adat\/fekvobeteg_szakellatas\/korhazi_agyszam.html."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., and Urb\u00e1n, E. (2019). Epidemiological Trends and Resistance Associated with Stenotrophomonas maltophilia Bacteremia: A 10-Year Retrospective Cohort Study in a Tertiary-Care Hospital in Hungary. Diseases, 7.","DOI":"10.3390\/diseases7020041"},{"key":"ref_49","unstructured":"Jousimies-Somer, H., Summanen, P., Citron, D.M., Baron, E.J., Wexler, H.M., and Finegold, S.M. (2003). Wadsworth-KTL Anaerobic Bacteriology Manual, Star Publishing Company. [6th ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., Spengler, G., and Urb\u00e1n, E. (2017). Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik\u2019s Cube of Clinical Microbiology?. Antibiotics, 6.","DOI":"10.3390\/antibiotics6040025"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., Urb\u00e1n, E., and Terhes, G. (2019). Microbiological and Clinical Aspects of Cervicofacial Actinomyces Infections: An Overview. Dent. J., 7.","DOI":"10.3390\/dj7030085"},{"key":"ref_52","first-page":"84","article-title":"Epidemiology and species distribution of anaerobic Gram-negative cocci: A 10-year retrospective survey (2008\u20132017)","volume":"89","year":"2019","journal-title":"Acta Pharm. Hung."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1128\/JCM.37.2.461-463.1999","article-title":"PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium difficile and construction of a library consisting of 116 different PCR ribotypes","volume":"37","author":"Stubbs","year":"1999","journal-title":"J. Clin. Microbiol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/1\/16\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:18:44Z","timestamp":1760361524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/9\/1\/16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,2]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["antibiotics9010016"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics9010016","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,2]]}}}