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Therapie des typischen hämolytisch-urämischen Syndroms

Erkenntnisse aus dem E.-coli-Ausbruch 2011

Treatment of typical hemolytic–uremic syndrome

Knowledge gained from analyses of the 2011 E. coli outbreak

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Zusammenfassung

Das Shiga-Toxin-assoziierte hämolytisch-urämische Syndrom (HUS) ist eine Form der thrombotischen Mikroangiopathie mit hämolytischer Anämie, Thrombozytopenie und akuter Nierenschädigung. Im Mai 2011 kam es in Norddeutschland zu einem Ausbruch mit enterohämorrhagischen Escherichia  coli (EHEC; O104:H4). Ende Juli waren fast 4000 Patienten an einer EHEC-Infektion erkrankt. Dem Robert Koch-Institut wurden 855 Patienten mit der Diagnose eines HUS gemeldet, 35 (4,1%) starben. Das EHEC-assoziierte HUS ist eine meist sporadisch auftretende Erkrankung. Kontrollierte Therapiestudien liegen nicht vor. Erste Analysen lassen vermuten, dass der bei einem Großteil der Patienten eingesetzte Plasmaaustausch eher schädigend als therapeutisch erfolgreich war. Die Rolle des monoklonalen Antikörpers Eculizumab, eines Inhibitors des Komplementsystems, wird in einer noch unveröffentlichten Multicenterstudie geprüft. Vielversprechend könnte der Einsatz einiger Antibiotika zu bewerten sein. Dies würde einen Paradigmenwechsel in Bezug auf bisherige Therapiestrategien bedeuten. Weitere laufende und geplante Analysen der Epidemie sollten abgewartet werden, bevor eine endgültige Empfehlung zu den verschiedenen Therapieverfahren erfolgt.

Abstract

Shiga toxin-associated hemolytic uremic syndrome (HUS) is an entity of thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, central nervous symptoms, and renal insufficiency. In May 2011, an outbreak of enterohemorrhagic Escherichia coli (EHEC; O104:H4) occurred in Northern Germany. By the end of July 2011, the outbreak was over but nearly 4000 patients had an EHEC infection, 855 cases of hemolytic–uraemic syndrome were reported to the Robert Koch Institute, and there were 35 (4.1%) deaths. Shiga toxin-induced HUS is a rare disease and no controlled clinical trials on therapeutic options are available. First analyses of this outbreak suggest that therapeutic plasma exchange, which was used in the majority of patients, had no benefit and might even be harmful. The role of eculizumab, a monoclonal antibody which inhibits the complement system, is being examined in a multicenter study: the results have not been published yet. Promising is the use of some antibiotics. This would change a paradigm that antibiotics should be avoided. Ongoing and future analyses of the epidemic should be awaited before a final recommendation regarding the different treatment strategies can be made.

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Literatur

  1. Magnus T, Rother J, Simova O et al (2012) The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. Brain 135:1850–1859

    Article  PubMed  Google Scholar 

  2. Trachtman H, Austin C, Lewinski M, Stahl RAK (2012) Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol 8:658–669

    Article  PubMed  CAS  Google Scholar 

  3. Weissenborn K, Donnerstag F, Kielstein JT et al (2012) Neurologic manifestations of E. coli infection-induced hemolytic-uremic syndrome in adults. Neurology 79:1466–1473

    Article  PubMed  Google Scholar 

  4. Stahl AL, Sartz L, Karpman D (2011) Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 117:5503–5513

    Article  PubMed  Google Scholar 

  5. Harendza S (2011) „HUS diary“ of a German nephrologist during the current EHEC outbreak in Europe. Kidney Int 80:687–689

    Article  PubMed  Google Scholar 

  6. (o A) (2011) Abschließende Darstellung und Bewertung der epidemiologischen Erkenntnisse im EHEC O104:H4 Ausbruch. Deutschland 2011. http://www.rki.de/DE/Content/InfAZ/E/EHEC/EHEC-Abschlussbericht.pdf?__blob=publicationFile

  7. Bielaszewska M, Mellmann A, Zhang W et al (2011) Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11:671–676

    PubMed  CAS  Google Scholar 

  8. Rohde H, Qin J, Cui Y et al (2011) Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4. N Engl J Med 365:718–724

    Article  PubMed  CAS  Google Scholar 

  9. Rasko DA, Webster DR, Sahl JW et al (2011) Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. N Engl J Med 365:709–717

    Google Scholar 

  10. Frank C, Werber D, Cramer JP et al (2011) Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany – preliminary report. N Engl J Med 365:1771–1780

    Google Scholar 

  11. Hickey CA, Beattie TJ, Cowieson J et al (2011) Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome. Arch Pediatr Adolesc Med 165:884–889

    Article  PubMed  Google Scholar 

  12. Kielstein JT, Beutel G, Fleig S et al (2012) Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant 27:3807–3815

    Article  PubMed  CAS  Google Scholar 

  13. Deutsche Gesellschaft für Nephrologie (DGfN) (2011) Therapeutische Apheresebehandlung bei EHEC assoziiertem HUS. http://www.dgfn.eu/indexphp?eID=tx_nawsecuredl&u=0&file=uploads/media/Apheresebehandlung_bei_EHEC_assoziiertem_HUSpdf&t=1319206713&hash=f151eac68f20e001487b481800ceacfb40991f70

  14. Szczepiorkowski ZM, Winters JL, Bandarenko N et al (2010) Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher 25:83–177

    Google Scholar 

  15. Te Loo DM, Hinsbergh VW van, Heuvel LP van den, Monnens LA (2001) Detection of verocytotoxin bound to circulating polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol 12:800–806

    Google Scholar 

  16. Dundas S, Murphy J, Soutar RL et al (1999) Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 354:1327–1330

    Article  PubMed  CAS  Google Scholar 

  17. Bambauer R, Latza R, Schiel R (2011) Therapeutic apheresis in the treatment of hemolytic uremic syndrome in view of pathophysiological aspects. Ther Apher Dial 15:10–19

    Article  PubMed  Google Scholar 

  18. Loirat C, Sonsino E, Hinglais N et al (1988) Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol 2:279–285

    Article  PubMed  CAS  Google Scholar 

  19. Rizzoni G, Claris-Appiani A, Edefonti A et al (1988) Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial. J Pediatr 112:284–290

    Google Scholar 

  20. Loos S, Ahlenstiel T, Kranz B et al (2012) An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis 55:753–759

    Article  PubMed  CAS  Google Scholar 

  21. Menne J, Nitschke M, Stingele R et al (2012) Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study. BMJ 345:e4565

    Article  PubMed  Google Scholar 

  22. Ruggenenti P, Remuzzi G (2011) A German outbreak of haemolytic uraemic syndrome. Lancet 378:1057–1058

    Article  PubMed  Google Scholar 

  23. Greinacher A, Friesecke S, Abel P et al (2011) Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial. Lancet 378:1166–1173

    Article  PubMed  Google Scholar 

  24. Combe C, Bui H, Precigout V de et al (2011) Immunoadsorption in patients with haemolytic uraemic syndrome. Lancet 379:517–518 (Autorenantwort 518–519)

    Article  Google Scholar 

  25. Pietrement C, Bednarek N, Baudouin V et al (2012) Immunoadsorption for paediatric post-diarrhoea haemolytic-uraemic syndrome with severe neurological involvement. Clin Kidney J 5:484–485

    Article  Google Scholar 

  26. Ashkenazi S, Cleary TG, Lopez E, Pickering LK (1988) Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome. J Pediatr 113:1008–1014

    Google Scholar 

  27. Wong CS, Jelacic S, Habeeb RL et al (2000) The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342:1930–1936

    Google Scholar 

  28. Panos GZ, Betsi GI, Falagas ME (2006) Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection? Aliment Pharmacol Ther 24:731–742

    Article  PubMed  CAS  Google Scholar 

  29. Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073–1086

    PubMed  CAS  Google Scholar 

  30. Safdar N, Said A, Gangnon RE, Maki DG (2002) Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 288:996–1001

    Article  PubMed  Google Scholar 

  31. Nitschke M, Sayk F, Hartel C et al (2012) Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA 307:1046–1052

    Article  PubMed  CAS  Google Scholar 

  32. Bielaszewska M, Idelevich EA, Zhang W et al (2012) Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain. Antimicrob Agents Chemother 56:3277–3282

    Article  PubMed  CAS  Google Scholar 

  33. Nurnberger J, Philipp T, Witzke O et al (2009) Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med 360:542–544

    Google Scholar 

  34. Lapeyraque AL, Malina M, Fremeaux-Bacchi V et al (2011) Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 364:2561–2563

    Google Scholar 

  35. Tschumi S, Gugger M, Bucher BS et al (2011) Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol 26:2085–2088

    Article  PubMed  Google Scholar 

  36. Noris M, Remuzzi G (2009) Atypical hemolytic-uremic syndrome. N Engl J Med 361:1676–1687

    Google Scholar 

  37. Bell BP, Griffin PM, Lozano P et al (1997) Predictors of hemolytic uremic syndrome in children during a large outbreak of Escherichia coli O157:H7 infections. Pediatrics 100:E12

    Article  PubMed  CAS  Google Scholar 

  38. Slutsker L, Ries AA, Maloney K et al (1998) A nationwide case-control study of Escherichia coli O157:H7 infection in the United States. J Infect Dis 177:962–966

    Article  PubMed  CAS  Google Scholar 

  39. Cimolai N, Basalyga S, Mah DG et al (1994). A continuing assessment of risk factors for the development of Escherichia coli O157:H7-associated hemolytic uremic syndrome. Clin Nephrol 42:85–89

    PubMed  CAS  Google Scholar 

  40. Ostroff SM, Kobayashi JM, Lewis JH (1989) Infections with Escherichia coli O157:H7 in Washington State. The first year of statewide disease surveillance. JAMA 262:355–359

    Article  PubMed  CAS  Google Scholar 

  41. Pavia AT, Nichols CR, Green DP et al (1990) Hemolytic-uremic syndrome during an outbreak of Escherichia coli O157:H7 infections in institutions for mentally retarded persons: clinical and epidemiologic observations. J Pediatr 116:544–551

    Google Scholar 

  42. Ikeda K, Ida O, Kimoto K et al (1999) Effect of early fosfomycin treatment on prevention of hemolytic uremic syndrome accompanying Escherichia coli O157:H7 infection. Clin Nephrol 52:357–362

    PubMed  CAS  Google Scholar 

  43. Proulx F, Turgeon JP, Delage G et al (1992) Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. J Pediatr 121:299–303

    Google Scholar 

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Interessenkonflikt

Die korrespondierenden Autoren weisen für sich und ihre Koautoren auf folgende Beziehungen hin: Menne, Stahl: Teilnahme an der von Alexion gesponserten Studie; Menne: Vortragshonorar Alexion.

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Authors and Affiliations

  1. Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    J. Menne & J.T. Kielstein

  2. III. Medizinische Klinik und Poliklinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20251, Hamburg-Eppendorf, Deutschland

    U. Wenzel &  R.A.K. Stahl

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  1. J. Menne
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  2. J.T. Kielstein
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  3. U. Wenzel
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  4. R.A.K. Stahl
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Correspondence to J. Menne or R.A.K. Stahl.

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Menne, J., Kielstein, J., Wenzel, U. et al. Therapie des typischen hämolytisch-urämischen Syndroms. Internist 53, 1420–1430 (2012). https://doi.org/10.1007/s00108-012-3107-5

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