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DOI: 10.1055/a-0729-3168
Aktuelle Konzepte zur Diagnostik und Therapie der Clostridioides [Clostridium]-difficile-Infektion bei Patienten mit chronisch-entzündlichen Darmerkrankungen
Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel diseasePublication History
08 June 2018
19 August 2018
Publication Date:
12 November 2018 (online)
Zusammenfassung
Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) haben ein deutlich erhöhtes Risiko für Clostridioides [Clostridium] difficile Infektionen (CDI). Eine CDI kann ihrerseits die Aktivität der luminalen Entzündung erhöhen. Daher ist eine rasche Diagnostik und Therapie erforderlich. Viele Diagnose- und Behandlungsstudien zu Patienten mit CDI ohne entzündliche Darmerkrankung lassen sich nicht deckungsgleich auf CED-Patienten übertragen. Diese Übersicht fasst deshalb die alltagsrelevanten Daten der letzten Jahre zusammen und kondensiert diese in vier Leitsätzen. 1) Eine CDI verschlechtert nicht nur kurzfristig die Krankheitsaktivität, sondern bedingt langfristig eine erhöhte Morbidität (z. B. Kolektomiegefahr) und Mortalität. 2) Bei Verdacht auf eine CDI sollte rasch ein Glutamat-Dehydrogenase (GDH)-Nachweis geführt werden. Ist dieser positiv und ist die Krankheitsaktivität hoch, ist eine Therapie gegen C. diff. einzuleiten und diese ggf. bei negativen Bestätigungstests zu beenden. 3) CED-Patienten mit einer nachgewiesenen CDI sollten primär mit Vancomycin behandelt werden. 4) Bei einer rezidivierenden CDI bei Patienten mit CED ist der fäkale Mikrobiomtransfer eine effektive Therapiemaßnahme. Allerdings muss in ca. 15 % der Fälle mit einer Aktivierung der CED gerechnet werden. Ein konsequentes Beachten dieser Leitsätze kann im Umgang mit einer CDI bei CED-Patienten helfen.
Abstract
Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and—if necessary—terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.
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Literatur
- 1 Lawson PA, Citron DM, Tyrrell KL. et al. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prevot 1938. Anaerobe 2016; 40: 95-99
- 2 Lessa FC, Mu Y, Bamberg WM. et al. Burden of Clostridium difficile infection in the United States. The New England journal of medicine 2015; 372: 825-834
- 3 Savidge TC, Urvil P, Oezguen N. et al. Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nature medicine 2011; 17: 1136-1141
- 4 Rodemann JF, Dubberke ER, Reske KA. et al. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2007; 5: 339-344
- 5 Trnka YM, LaMont JT. Association of Clostridium difficile toxin with symptomatic relapse of chronic inflammatory bowel disease. Gastroenterology 1981; 80: 693-696
- 6 Ott C, Girlich C, Klebl F. et al. Low risk of Clostridium difficile infections in hospitalized patients with inflammatory bowel disease in a German tertiary referral center. Digestion 2011; 84: 187-192
- 7 Barber GE, Hendler S, Okafor P. et al. Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis. Inflammatory bowel diseases 2018; DOI: 10.1093/ibd/izy086.
- 8 Kistangari G, Lopez R, Shen B. Frequency and Risk Factors of Clostridium difficile Infection in Hospitalized Patients With Pouchitis: A Population-based Study. Inflammatory bowel diseases 2017; 23: 661-671
- 9 Issa M, Vijayapal A, Graham MB. et al. Impact of Clostridium difficile on inflammatory bowel disease. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2007; 5: 345-351
- 10 Razik R, Rumman A, Bahreini Z. et al. Recurrence of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease: The RECIDIVISM Study. The American journal of gastroenterology 2016; 111: 1141-1146
- 11 Singh H, Nugent Z, Yu BN. et al. Higher Incidence of Clostridium difficile Infection Among Individuals With Inflammatory Bowel Disease. Gastroenterology 2017; 153: 430-438 e432
- 12 Joshi NM, Marks IH, Crowson R. et al. Incidence and Outcome of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease in the UK. Journal of Crohn’s & colitis 2017; 11: 70-76
- 13 Nguyen GC, Kaplan GG, Harris ML. et al. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. The American journal of gastroenterology 2008; 103: 1443-1450
- 14 Yanai H, Nguyen GC, Yun L. et al. Practice of gastroenterologists in treating flaring inflammatory bowel disease patients with clostridium difficile: antibiotics alone or combined antibiotics/immunomodulators?. Inflammatory bowel diseases 2011; 17: 1540-1546
- 15 Rahier JF, Magro F, Abreu C. et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. Journal of Crohn’s & colitis 2014; 8: 443-468
- 16 Hagel S, Epple HJ, Feurle GE. et al. S2k-guideline gastrointestinal infectious diseases and Whipple’s disease. Zeitschrift fur Gastroenterologie 2015; 53: 418-459
- 17 Harbord M, Eliakim R, Bettenworth D. et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. Journal of Crohn’s & colitis 2017; 11: 769-784
- 18 Khanna S, Shin A, Kelly CP. Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2017; 15: 166-174
- 19 Martinelli M, Strisciuglio C, Veres G. et al. Clostridium difficile and pediatric inflammatory bowel disease: a prospective, comparative, multicenter, ESPGHAN study. Inflammatory bowel diseases 2014; 20: 2219-2225
- 20 Bhandari S, Mohammed Abdul MK, Dhakal B. et al. Increased Rate of Venous Thromboembolism in Hospitalized Inflammatory Bowel Disease Patients with Clostridium Difficile Infection. Inflammatory bowel diseases 2017; 23: 1847-1852
- 21 Law CC, Tariq R, Khanna S. et al. Systematic review with meta-analysis: the impact of Clostridium difficile infection on the short- and long-term risks of colectomy in inflammatory bowel disease. Alimentary pharmacology & therapeutics 2017; 45: 1011-1020
- 22 Anderson A, Click B, Ramos-Rivers C. et al. Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease: A Propensity Score Matched Analysis. Inflammatory bowel diseases 2017; 23: 2180-2188
- 23 Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut 2008; 57: 205-210
- 24 Ricciardi R, Ogilvie Jr JW, Roberts PL. et al. Epidemiology of Clostridium difficile colitis in hospitalized patients with inflammatory bowel diseases. Diseases of the colon and rectum 2009; 52: 40-45
- 25 Jen MH, Saxena S, Bottle A. et al. Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics 2011; 33: 1322-1331
- 26 Takahashi M, Mori N, Bito S. Multi-institution case-control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan. BMJ open 2014; 4: e005665
- 27 Kroner PT, Corral JE, Abougergi M. et al. The In-hospital Mortality Rate for Clostridium difficile Infection has Decreased Over the Past Decade in the United States: A 10-Year Nationwide Analysis. UEG Journal 2017; DOI: P735.
- 28 Kucharzik T, Dignass A, Atreya R. et al. S3-Leitlinie – Colitis ulcerosa. 2018 Sep 11. DOI: 10.1055/a-0651-8174 [Epub ahead of print] German
- 29 Debast SB, Bauer MP, Kuijper EJ. et al. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2014; 20: 1-26
- 30 Cheng JW, Xiao M, Kudinha T. et al. The Role of Glutamate Dehydrogenase (GDH) Testing Assay in the Diagnosis of Clostridium difficile Infections: A High Sensitive Screening Test and an Essential Step in the Proposed Laboratory Diagnosis Workflow for Developing Countries like China. PloS one 2015; 10: e0144604
- 31 Sokol H, Lalande V, Landman C. et al. Clostridium difficile infection in acute flares of inflammatory bowel disease: A prospective study. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2017; 49: 643-646
- 32 Erb S, Frei R, Stranden AM. et al. Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2015; 21: 998.e9-998
- 33 Deshpande A, Pasupuleti V, Patel P. et al. Repeat stool testing for Clostridium difficile using enzyme immunoassay in patients with inflammatory bowel disease increases diagnostic yield. Current medical research and opinion 2012; 28: 1553-1560
- 34 Yu L, Li H, Zhao X. et al. Rapid visual detection of binary toxin producing Clostridium difficile by loop-mediated isothermal amplification. Experimental and therapeutic medicine 2017; 14: 4781-4788
- 35 Elliott B, Chang BJ, Golledge CL. et al. Clostridium difficile-associated diarrhoea. Internal medicine journal 2007; 37: 561-568
- 36 Ben-Horin S, Margalit M, Bossuyt P. et al. Prevalence and clinical impact of endoscopic pseudomembranes in patients with inflammatory bowel disease and Clostridium difficile infection. Journal of Crohn’s & colitis 2010; 4: 194-198
- 37 Law ST, Yip WM, Li KK. Clinical significance of asymptomatic clostridium difficile carriage in patients on immunomodulator for inflammatory bowel disease. UEG journal 2017; 5: A289
- 38 Khanafer N, Barbut F, Eckert C. et al. Factors predictive of severe Clostridium difficile infection depend on the definition used. Anaerobe 2016; 37: 43-48
- 39 Horton HA, Dezfoli S, Berel D. et al. Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease. Antimicrobial agents and chemotherapy 2014; 58: 5054-5059
- 40 Pepin J, Alary ME, Valiquette L. et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2005; 40: 1591-1597
- 41 Gawronska A, Banasiuk M, Lachowicz D. et al. Metronidazole or Rifaximin for Treatment of Clostridium difficile in Pediatric Patients with Inflammatory Bowel Disease: A Randomized Clinical Trial. Inflammatory bowel diseases 2017; 23: 2209-2214
- 42 Rokas KE, Johnson JW, Beardsley JR. et al. The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2015; 61: 934-941
- 43 Erikstrup LT, Aarup M, Hagemann-Madsen R. et al. Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination. BMJ open gastroenterology 2015; 2: e000038
- 44 Li R, Lu L, Lin Y. et al. Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis. PloS one 2015; 10: e0137252
- 45 Herpers BL, Vlaminckx B, Burkhardt O. et al. Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2009; 48: 1732-1735
- 46 Britt NS, Steed ME, Potter EM. et al. Tigecycline for the Treatment of Severe and Severe Complicated Clostridium difficile Infection. Infectious diseases and therapy 2014; 3: 321-331
- 47 Knafl D, Winhofer Y, Lotsch F. et al. Tigecycline as last resort in severe refractory Clostridium difficile infection: a case report. The Journal of hospital infection 2016; 92: 296-298
- 48 Di Bella S, Nisii C, Petrosillo N. Is tigecycline a suitable option for Clostridium difficile infection? Evidence from the literature. International journal of antimicrobial agents 2015; 46: 8-12
- 49 Louie TJ, Miller MA, Mullane KM. et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. The New England journal of medicine 2011; 364: 422-431
- 50 Cornely OA, Crook DW, Esposito R. et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. The Lancet Infectious diseases 2012; 12: 281-289
- 51 Högenauer C, Mahida Y, Stallmach A. et al. Open-label study to evaluate the pharmacokinetics of fidaxomicin in inflammatory bowel disease patients with Clostridium difficile infection (the PROFILE study): pharmacokinetics analysis. JCC 2017; 11: S276
- 52 Spiceland CM, Khanna S, Pardi DS. Outcomes With Fidaxomicin Therapy in Clostridium difficile Infection. Journal of clinical gastroenterology 2018; 52: 151-154
- 53 Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. The Journal of infection 2009; 58: 403-410
- 54 Gianotti RJ, Moss AC. The Use and Efficacy of Fecal Microbiota Transplantation for Refractory Clostridium difficile in Patients with Inflammatory Bowel Disease. Inflammatory bowel diseases 2016; 22: 2704-2710
- 55 Chen T, Zhou Q, Zhang D. et al. Effect of Faecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Cohort Studies. Journal of Crohn’s & colitis 2018; 12: 710-717
- 56 Hagel S, Fischer A, Ehlermann P. et al. Fecal microbiota transplant in patients with recurrent Clostridium difficile infection—a retrospective multicenter observational study from the MicroTrans registry. Deutsches Ärzteblatt international 2016; 113: 583-589
- 57 Khoruts A, Rank KM, Newman KM. et al. Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2016; 14: 1433-1438
- 58 Fischer M, Kao D, Kelly C. et al. Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Inflammatory bowel diseases 2016; 22: 2402-2409
- 59 Teich N, Weber M, Stallmach A. First Occurrence of Severe Extraintestinal Manifestations of Crohn’s Disease Following Faecal Microbiota Transplantation. Journal of Crohn’s & colitis 2016; 10: 1254-1255
- 60 Qazi T, Amaratunga T, Barnes EL. et al. The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis. Gut microbes 2017; 8: 574-588
- 61 Stallmach A, Carstens O. Role of infections in the manifestation or reactivation of inflammatory bowel diseases. Inflammatory bowel diseases 2002; 8: 213-218
- 62 Ben-Horin S, Margalit M, Bossuyt P. et al. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2009; 7: 981-987
- 63 Ananthakrishnan AN, Guzman-Perez R, Gainer V. et al. Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics 2012; 35: 789-795
- 64 Stallmach A, Anttila VJ, Hell M. et al. Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals. Zeitschrift fur Gastroenterologie 2018; DOI: 10.1055/s-0044-100045.
- 65 Surawicz CM, Brandt LJ, Binion DG. et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. The American journal of gastroenterology 2013; 108: 478-498; quiz 499
- 66 Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms. The Journal of antimicrobial chemotherapy 2018; 73: 265-279
- 67 Shen NT, Maw A, Tmanova LL. et al. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology 2017; 152: 1889-1900 e1889
- 68 Mills JP, Rao K, Young VB. Probiotics for prevention of Clostridium difficile infection. Curr Opin Gastroenterol 2018; 34: 3-10
- 69 Goldenberg JZ, Yap C, Lytvyn L. et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. The Cochrane database of systematic reviews 2017; 12: CD006095
- 70 Allen SJ, Wareham K, Wang D. et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet (London, England) 2013; 382: 1249-1257
- 71 Gerding DN, Meyer T, Lee C. et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. Jama 2015; 313: 1719-1727
- 72 Kabbani TA, Pallav K, Dowd SE. et al. Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers. Gut microbes 2017; 8: 17-32
- 73 Zhang DM, Xu BB, Yu L. et al. A prospective control study of Saccharomyces boulardii in prevention of antibiotic-associated diarrhea in the older inpatients. Zhonghua Nei Ke Za Zhi 2017; 56: 398-401
- 74 Roberts T, Kokai-Kun JF, Coughlin O. et al. Tolerability and Pharmacokinetics of SYN-004, an Orally Administered β-Lactamase for the Prevention of Clostridium difficile-Associated Disease and Antibiotic-Associated Diarrhea, in Two Phase 1 Studies. Clin Drug Investig 2016; 36: 725-734
- 75 Kaleko M, Bristol JA, Hubert S. et al. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection. Anaerobe 2016; 41: 58-67
- 76 Wilcox MH, Gerding DN, Poxton IR. et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. The New England journal of medicine 2017; 376: 305-317