Clostridium difficile Infections and their Treatment

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http://urn.fi/URN:ISBN:978-952-10-9327-2
Title: Clostridium difficile Infections and their Treatment
Author: Mattila, Eero
Contributor: University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Medicine
Division of Infectious diseases and Division of Gastroenterology
Publisher: Helsingin yliopisto
Date: 2013-10-25
Language: en
URI: http://urn.fi/URN:ISBN:978-952-10-9327-2
http://hdl.handle.net/10138/41007
Thesis level: Doctoral dissertation (article-based)
Abstract: Background and aims. Standard treatment of recurrent Clostridium difficileinfection (CDI) with antibiotics leads to recurrences in up to 50% of patients.In recent years the incidence and mortality of Clostridium difficile (C.difficile)enteritis have increased. Nevertheless, C.difficile has rarely been isolated in extraintestinal infections. The aims of the study were to investigate efficacy of rifaximin, metronidazole, fecal microbiota transplantation (FMT) and Clostridium difficile immune whey (CDIW) in the treatment of recurrent CDI and to characterize clinical feature and risk factors for extra-intestinal CDI. Subjects and methods. Study I was a prospective, randomized, double-blind study designed to compare CDIW with metronidazole for treatment of laboratory confirmed,mild to moderate episodes of recurrent CDI. CDIW was manufactured by immunization of cows in their gestation period with inactivated C. difficile vaccine.The resulting colostrum was processed, immunoglubulins were concentrated and the end product containing high titres of C. difficile immunoglobulin was used as CDIW. 20 patients received metronidazole at a dosage of 400 mg t.i.d. and 18 patients CDIW 200 ml t.i.d. Study II was a retrospective review of 70 patients with recurrent CDI who had undergone fecal transplantation. FMT was performed at colonoscopy by infusing fresh donor feces into cecum. Before transplantation, the patients had whole-bowel lavage with polyethylene glycol solution. Study III was a retrospective study of 32 patients who were treated with rifaximin for recurrent CDI. In Study IV extra-intestinal CDIs were searched for in an electronic database of all C. difficile positive isolates found during a 10-year period. The medical records were reviewed retrospectively. Disease severity and co-morbidities of the patients were evaluated using Horn disease severity and Charlson co-morbidity indexes. Results. In Study I, 10 weeks after the beginning of treatment, sustained responses were observed in 11 (55%) of 20 patients receiving metronidazole and 10(56%) of 18 patients treated with CDIW. In Study II, 12 weeks after FMT, 66 (94%)of 70 patients had a favourable response. In Study III, 12 weeks after rifaximin treatment 17 (53%) of 30 patients had no relapse. In Study IV extra-intestinal CDI was found in 31 patients who comprised 0.17% of all CDIs. One-year mortalityrate was 36% and it correlated with the severity of underlying diseases Conclusions. CDIW was as effective as metronidazole in the prevention of CDI recurrences and it was well tolerated. FMT through colonoscopy seems to be an effective treatment also for recurrent CDI caused by the virulent C difficile 027 strain. The MIC value of rifampin seemed to predict the response to rifaximin treatment. Extra-intestinal CDIs occur mainly in hospitalized patients with significant comorbidities.Extra-intestinal CDIs in the abdominal area may result either from intestinal perforation after infection or after intestinal surgery. C. difficile may reach distant sites via bacteremia. Mortality in extra-intestinal CDIs is associated with the severity of underlying diseasesClostridium difficile on suolistobakteeri, joka pystyy parhaiten lisääntymään muun suoliston bakteeriston vaurioiduttua, eli useimmiten antibioottikuurin aikana tai pian sen jälkeen. Perinteisesti C. difficile -infektioita on hoidettu joko metronidatsolilla tai vankomysiinillä. Nämä molemmat ovat antibiootteja, jotka vaikuttavat myös suoliston normaalin bakteerikantaan, altistaen ripulin uusiutumiselle. Osittain tästä johtuen C difficile -infektio uusiutuu 15%-35%:lla niistä, joilla on ollut yksi edeltävä suoliston tulehdus ja 33%-65%:lla, joilla on ollut kaksi tai useampaa tulehdusta. Viime vuosina C. difficile infektion luonne on muuttunut, taudin ilmaantuvuus, vakavien tapausten osuus ja kuolleisuus ovat lisääntyneet. Vuonna 2012 THL:n tartuntatautirekisteriin ilmoitettiin 5259 tapausta. Tutkimuksen tavoitteena oli tutkia hyvin erilaisilla vaiktusmekanismeilla vaikuttavien hoitojen tehoa, eli antibioottien kuten rifaksiimin ja metronidatsolin, bakteerihoidon eli ulosteensiirron sekä vasta-ainehoidon, eli immuunimaidon tehoa uusiutuvan C. diffile-infektion hoidossa. Lisäksi tutkittiin suoliston ulkopuolisen C. difficile infektion riskitekijöitä ja taudinkuvaa. Immuunimaito valmistettiin rokottomalla tiineenä olevia lehmiä, ja vasta-aineet kerättiin ternimaidosta. Ulosteensiirto suoritettiin ruiskuttamalla tuore siirre paksusuolen tähystimen kautta paksusuolen alkuosaan. Ennen siirtoa potilaiden paksusuoli oli tyhjennetty tavanomaisin paksusuolen tähýstyksiin liittyvin menetelmin. Kaikki HUS-piirin suoliston ulkopuoliset C. difficile-infektiot arvioitiin 10 vuoden ajalta. Ulosteensiirrolla 94 % potilaista parani, immuunimaidolla parani 56 %, metronidatsoli-antibiootilla 55 % ja rifaksiimi-antibiootilla 53 %.Ulosteensiirron hoitotulokset olivat parhaita. Ulosteensiirto oli myös tehokas vaikeisiin C. difficile 027 bakteerikantoihin. Suoliston ulkopuolisia löydöksiä oli 0.17 %:lla kaikista C. difficile potilaista. 36 % potilaista kuoli vuoden seurannan aikana. Kuolleisuus oli yhteydessä taustalla olevan perustaudin vaikeusasteeseen. Useimmiten suoliston ulkopuolisen infektion taustalla oli joko suoliston puhkeama tai leikkauksen jälkeinen infektio. C. difficile voi myös aiheuttaa verenmyrkytyksiä ja haavainfektioita.
Subject: lääketiede
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