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Zentralbl Chir 2014; 139(4): 460-468
DOI: 10.1055/s-0032-1328623
Originalarbeit
Georg Thieme Verlag KG Stuttgart · New York

Clostridium-difficile-Infektionen (CDI) im Wandel der Zeit – ein Thema nur für den Internisten?

Clostridium difficile Infection (CDI) in the Course of Time – An Issue Only for the Internist?
S. Weis
1   Department für Innere Medizin, Neurologie und Dermatologie, Klinik für Gastroenterologie und Rheumatologie, Universität Leipzig, Leipzig, Deutschland
,
E. John
2   Chirurgie, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Deutschland
,
N. Lippmann
3   Institut für Medizinische Mikrobiologie, Universität Leipzig, Leipzig, Deutschland
,
J. Mössner
1   Department für Innere Medizin, Neurologie und Dermatologie, Klinik für Gastroenterologie und Rheumatologie, Universität Leipzig, Leipzig, Deutschland
,
C. Lübbert
1   Department für Innere Medizin, Neurologie und Dermatologie, Klinik für Gastroenterologie und Rheumatologie, Universität Leipzig, Leipzig, Deutschland
4   Fachbereich Infektions- und Tropenmedizin, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland
› Author Affiliations
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Publication History

Publication Date:
16 October 2013 (online)

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Erratum: Clostridium-difficile-Infektionen (CDI) im Wandel der Zeit – ein Thema nur für den Internisten?Zentralbl Chir 2014; 139(04): e26-e26
DOI: 10.1055/s-0034-1368432

Zusammenfassung

Hintergrund: Toxinbildende Clostridium-(C.)-difficile-Stämme sind weltweit die häufigsten Erreger von antibiotikaassoziierten Darmerkrankungen und nosokomialer Diarrhö. In den letzten 10 Jahren wurde ein kontinuierlicher Inzidenzanstieg von C.-difficile-Infektionen (CDI) beobachtet.
Material und Methoden: Mit klinischen und mikrobiologischen Originaldaten der Jahre 2002–2012 aus den Universitätskliniken Leipzig und Halle (Saale) weisen die Autoren auf die aktuelle Situation hinsichtlich CDI in den Bundesländern Sachsen und Sachsen-Anhalt hin und stellen die neuesten Entwicklungen bezüglich Inzidenz, Resistenzsituation, Diagnostik und Therapie von CDI sowie die Indikationen für eine chirurgische Intervention dar.
Ergebnisse: Dem allgemeinen Trend entsprechend, ist auch an den Universitätskliniken Leipzig und Halle (Saale) ein Inzidenzanstieg von CDI, insbesondere von schweren klinischen Verlaufsformen, zu verzeichnen. Die Vermeidung von CDI stellt in erster Linie eine Herausforderung an das Hygienemanagement dar und erfordert einen gezielten, zurückhaltenden Einsatz von Antibiotika, möglichst in Form sogenannter „Antibiotic Stewardship“-Programme. Das neue Antibiotikum Fidaxomicin hat Ende 2012 das bislang vor allem aus Metronidazol oder Vancomycin bestehende therapeutische Armamentarium bezüglich CDI bereichert und vermag die Rezidivquote zu senken. Die Wiederherstellung einer Eubiose im Kolon von rezidivierenden CDI betroffener Patienten mittels Stuhltransplantation von gesunden Spendern stellt eine hochwirksame Alternative zur antibiotischen Therapie dar. Chirurgischer Standardeingriff bei therapierefraktärer CDI ist die subtotale Kolektomie mit endständigem Ileostoma. Bei Patienten mit adäquater Lebenserwartung und ohne Organversagen kann ein kolonerhaltendes bzw. -sparendes Verfahren erwogen werden.
Schlussfolgerung: Die Einnahme von Antibiotika bleibt für die meisten Patienten der Hauptrisikofaktor für das Erleiden einer symptomatischen CDI. Mit der Einführung von Fidaxomicin deutet sich eine Verbesserung in der konservativen Therapie von CDI an. Die im Vergleich zur antibiotischen Therapie von CDI bessere Wirksamkeit der Stuhltransplantation von gesunden Spendern gilt inzwischen als ausreichend gesichert, hat bislang aber keinen Eingang in den klinischen Alltag gefunden. Bei ausbleibendem Therapieerfolg muss frühzeitig der Chirurg hinzugezogen werden. Dabei ist die Evidenz für kolonerhaltende bzw. -sparende operative Verfahren bislang leider schmal.

Abstract

Background: Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide.
Materials and Methods: With clinical and microbiological original data for 2002–2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options.
Results: Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as “Antibiotic Stewardship” programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered.
Conclusion: Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low.

Schlüsselwörter

Clostridium difficile - Clostridium-difficile-Infektion (CDI) - Clostridium-difficile-assoziierte Diarrhö (CDAD) - Inzidenz - Kolektomie - Antibiotika

Key words

Clostridium difficile - Clostridium difficile infection (CDI) - Clostridium difficile associated diarrhea (CDAD) - incidence - colectomy - antibiotics
 

  • Literatur

  • 1 Hall IC, OʼToole E. Intestinal flora in newborn infants with description of a new pathogenic anaerobe. Am J Dis Child 1935; 49: 390-402
    CrossrefPubMedSearch in Google Scholar
  • 2 Bartlett JG, Chang TW, Gurwith M et al. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med 1978; 298: 531-534
    CrossrefPubMedSearch in Google Scholar
  • 3 Larson HE, Price AB, Honour P et al. Clostridium difficile and the aetiology of pseudomembranous colitis. Lancet 1978; 1: 1063-1066
    PubMedSearch in Google Scholar
  • 4 Kyne L, Hamel MB Polavaram Ret al. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002; 34: 346-353
    CrossrefPubMedSearch in Google Scholar
  • 5 Vonberg RP, Reichardt C, Behnke M et al. Costs of nosocomial Clostridium difficile-associated diarrhoea. J Hosp Infect 2008; 70: 15-20
    PubMedSearch in Google Scholar
  • 6 Hensgens MP, Goorhuis A, Dekkers OM et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2011; 67: 742-748
    PubMedSearch in Google Scholar
  • 7 Bauer MP, Notermans DW, van Benthem BH et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet 2011; 377: 63-73
    CrossrefPubMedSearch in Google Scholar
  • 8 Grünewald T, Kist M, Mutters R et al. [Clostridium difficile infection]. Dtsch Med Wochenschr 2010; 135: 699-703
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Reichardt C, Chaberny IF, Kola A et al. [Dramatic increase of Clostridium difficile-associated diarrhea in Germany: has the new strain PCR-ribotype 027 already reached us?]. Dtsch Med Wochenschr 2007; 132: 223-228
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Burckhardt F, Friedrich A, Beier D et al. Clostridium difficile surveillance trends, Saxony, Germany. Emerg Infect Dis 2008; 14: 691-692
    CrossrefPubMedSearch in Google Scholar
  • 11 DuPont HL. The search for effective treatment of Clostridium difficile infection. N Engl J Med 2011; 364: 473-475
    CrossrefPubMedSearch in Google Scholar
  • 12 Lo Vecchio A, Zacur GM. Clostridium difficile infection: an update on epidemiology, risk factors, and therapeutic options. Curr Opin Gastroenterol 2012; 28: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 13 Kuijper EJ, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006; 12 (Suppl. 06) S2-S18
    PubMedSearch in Google Scholar
  • 14 Aldeyab MA, Kearney MP, Scott MG et al. An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings. J Antimicrob Chemother 2012; 67: 2988-2996
    CrossrefPubMedSearch in Google Scholar
  • 15 Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31: 431-455
    CrossrefPubMedSearch in Google Scholar
  • 16 Ackermann G. Clostridium difficile – Aktueller Stand. Teil I: Epidemiologie, Pathogenese, Diagnostik, Therapie, Immunologie und Prophylaxe. Mikrobiologe 2004; 14: 123-129
    PubMedSearch in Google Scholar
  • 17 Raveh D, Rabinowitz B, Breuer GS. Risk factors for Clostridium difficile toxin-positive nosocomial diarrhoea. Int J Antimicrob Agents 2006; 28: 231-237
    CrossrefPubMedSearch in Google Scholar
  • 18 Morteau O, Castagliuolo I, Mykoniatis A et al. Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice. Gastroenterology 2002; 122: 725-733
    CrossrefPubMedSearch in Google Scholar
  • 19 Paredes-Sabja D, Sarker MR. Adherence of Clostridium difficile spores to Caco-2 cells in culture. J Med Microbiol 2012; 61: 1208-1218
    CrossrefPubMedSearch in Google Scholar
  • 20 Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect 2009; 58: 403-410
    CrossrefPubMedSearch in Google Scholar
  • 21 Lübbert C, Johann C, Kekulé AS et al. Immunsuppressive Behandlung als Risikofaktor für das Auftreten einer Clostridium difficile-Infektion (CDI). Z Gastroenterol 2013; 51: 1251-1258
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Robert Koch-Institut. Ratgeber Infektionskrankheiten – Merkblätter für Ärzte: Clostridium difficile. Epidemiol Bull 2009; 24: 233-239
    PubMedSearch in Google Scholar
  • 23 Bauer MP, van Dissel JT, Kuijper EJ. Clostridium difficile: controversies and approaches to management. Curr Opin Infect Dis 2009; 22: 517-524
    CrossrefPubMedSearch in Google Scholar
  • 24 Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Update of the treatment guidance document for Clostridium difficile-infection (CDI). Clin Microbiol Infect 2014; 20 (Suppl. 02) 1-26
    CrossrefPubMedSearch in Google Scholar
  • 25 Dansinger ML, Johnson S, Jansen PC et al. Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study. Clin Infect Dis 1996; 22: 932-937
    CrossrefPubMedSearch in Google Scholar
  • 26 RKI. Empfehlungen des Robert Koch-Institutes zu Hygienemaßnahmen bei Patienten mit Durchfällen aufgrund von toxinbildendem Clostridium difficile, Stand Dezember 2008.. Im Internet: http://www.rki.de/DE/Content/Infekt/Krankenhaushygiene/Erreger_ausgewaehlt/Clostridium.html Stand: 07.04.2013
    PubMed
  • 27 Bauer MP, Kuijper EJ, van Dissel JT. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect 2009; 15: 1067-1079
    CrossrefPubMedSearch in Google Scholar
  • 28 Gerding DN, Muto CA, Owens jr. RC. Treatment of Clostridium difficile infection. Clin Infect Dis 2008; 46 (Suppl. 01) S32-S42
    CrossrefPubMedSearch in Google Scholar
  • 29 Zar FA, Bakkanagari SR, Moorthi KM et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45: 302-307
    CrossrefPubMedSearch in Google Scholar
  • 30 Pepin J. Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic?. Clin Infect Dis 2008; 46: 1493-1498
    CrossrefPubMedSearch in Google Scholar
  • 31 Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2007; (9) CD004610
    PubMedSearch in Google Scholar
  • 32 Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev 2008; (1) CD004611
    PubMedSearch in Google Scholar
  • 33 Johnston BC, Ma SS, Goldenberg JZ et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med 2013; 157: 878-888
    PubMedSearch in Google Scholar
  • 34 Lowy I, Molrine DC, Leav BA et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010; 362: 197-205
    CrossrefPubMedSearch in Google Scholar
  • 35 Louie TJ, Miller MA, Mullane KM et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364: 422-431
    CrossrefPubMedSearch in Google Scholar
  • 36 Lübbert C. Fidaxomicin als Alternative zu Vancomycin bei Clostridium difficile-Infektion. Gastroenterologie up2date 2011; 7: 74-75
    Thieme ConnectPubMedSearch in Google Scholar
  • 37 Brandt LJ, Aroniadis OC, Mellow M et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 2012; 107: 1079-1087
    CrossrefPubMedSearch in Google Scholar
  • 38 van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013; 368: 407-415
    CrossrefPubMedSearch in Google Scholar
  • 39 Bhangu A, Nepogodiev D, Gupta A et al. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg 2012; 99: 1501-1513
    CrossrefPubMedSearch in Google Scholar
  • 40 Dallal RM, Harbrecht BG, Boujoukas AJ et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg 2002; 235: 363-372
    CrossrefPubMedSearch in Google Scholar
  • 41 Koss K, Clark MA, Sanders DS et al. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis 2006; 8: 149-154
    CrossrefPubMedSearch in Google Scholar
  • 42 Lamontagne F, Labbe AC, Haeck O et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007; 245: 267-272
    CrossrefPubMedSearch in Google Scholar
  • 43 Jaber MR, Olafsson S, Fung WL et al. Clinical review of the management of fulminant clostridium difficile infection. Am J Gastroenterol 2008; 103: 3195-3203 quiz 3204
    CrossrefPubMedSearch in Google Scholar
  • 44 Pepin J, Vo TT, Boutros M et al. Risk factors for mortality following emergency colectomy for fulminant Clostridium difficile infection. Dis Colon Rectum 2009; 52: 400-405
    CrossrefPubMedSearch in Google Scholar
  • 45 Carchman EH, Peitzman AB, Simmons RL et al. The role of acute care surgery in the treatment of severe, complicated Clostridium difficile-associated disease. J Trauma Acute Care Surg 2012; 73: 789-800
    CrossrefPubMedSearch in Google Scholar
  • 46 Synnott K, Mealy K, Merry C et al. Timing of surgery for fulminating pseudomembranous colitis. Br J Surg 1998; 85: 229-231
    CrossrefPubMedSearch in Google Scholar
  • 47 Longo WE, Mazuski JE, Virgo KS et al. Outcome after colectomy for Clostridium difficile colitis. Dis Colon Rectum 2004; 47: 1620-1626
    CrossrefPubMedSearch in Google Scholar
  • 48 Ali SO, Welch JP, Dring RJ. Early surgical intervention for fulminant pseudomembranous colitis. Am Surg 2008; 74: 20-26
    PubMedSearch in Google Scholar
  • 49 Byrn JC, Maun DC, Gingold DS et al. Predictors of mortality after colectomy for fulminant Clostridium difficile colitis. Arch Surg 2008; 143: 150-154 discussion 155
    CrossrefPubMedSearch in Google Scholar
  • 50 Butala P, Divino CM. Surgical aspects of fulminant Clostridium difficile colitis. Am J Surg 2010; 200: 131-135
    CrossrefPubMedSearch in Google Scholar
  • 51 Sailhamer EA, Carson K, Chang Y et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg 2009; 144: 433-439 discussion 439–440
    CrossrefPubMedSearch in Google Scholar
  • 52 Neal MD, Alverdy JC, Hall DE et al. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg 2011; 254: 423-427 discussion 427–429
    CrossrefPubMedSearch in Google Scholar
  • 53 Nassour I, Carchman EH, Simmons RL et al. Novel management strategies in the treatment of severe Clostridium difficile infection. Adv Surg 2012; 46: 111-135
    CrossrefPubMedSearch in Google Scholar
  • 54 Greenstein AJ, Byrn JC, Zhang LP et al. Risk factors for the development of fulminant Clostridium difficile colitis. Surgery 2008; 143: 623-629
    CrossrefPubMedSearch in Google Scholar
  • 55 Ricciardi R, Harriman K, Baxter NN et al. Predictors of Clostridium difficile colitis infections in hospitals. Epidemiol Infect 2008; 136: 913-921
    PubMedSearch in Google Scholar
  • 56 Al-Abed YA, Gray EA, Rothnie ND. Outcomes of emergency colectomy for fulminant Clostridium difficile colitis. Surgeon 2010; 8: 330-333
    CrossrefPubMedSearch in Google Scholar
  • 57 Miller AT, Tabrizian P, Greenstein AJ et al. Long-term follow-up of patients with fulminant Clostridium difficile colitis. J Gastrointest Surg 2009; 13: 956-959
    CrossrefPubMedSearch in Google Scholar