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Multicenter Study
. 2012 Jul 19:345:e4565.
doi: 10.1136/bmj.e4565.

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study

Jan Menne  1 , Martin Nitschke, Robert Stingele, Mariam Abu-Tair, Jan Beneke, Jörn Bramstedt, Jan P Bremer, Reinhard Brunkhorst, Veit Busch, Reinhard Dengler, Günther Deuschl, Klaus Fellermann, Helmut Fickenscher, Christoph Gerigk, Alexander Goettsche, Jobst Greeve, Carsten Hafer, Friedrich Hagenmüller, Hermann Haller, Stefan Herget-Rosenthal, Bernd Hertenstein, Christina Hofmann, Melanie Lang, Jan T Kielstein, Ulrich C Klostermeier, Johannes Knobloch, Markus Kuehbacher, Ulrich Kunzendorf, Hendrik Lehnert, Michael P Manns, Tobias F Menne, Tobias N Meyer, Claus Michael, Thomas Münte, Christine Neumann-Grutzeck, Jens Nuernberger, Hermann Pavenstaedt, Leyla Ramazan, Lutz Renders, Jonas Repenthin, Wolfgang Ries, Axel Rohr, Lars Christian Rump, Ola Samuelsson, Friedhelm Sayk, Bernhard M W Schmidt, Sabine Schnatter, Harald Schöcklmann, Stefan Schreiber, Cay U von Seydewitz, Jürgen Steinhoff, Sylvia Stracke, Sebastian Suerbaum, Andreas van de Loo, Martin Vischedyk, Karin Weissenborn, Peter Wellhöner, Monika Wiesner, Sebastian Zeissig, Jürgen Büning, Mario Schiffer, Tanja Kuehbacher; EHEC-HUS consortium
Collaborators, Affiliations
Multicenter Study

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study

Jan Menne et al. BMJ. .

Abstract

Objective: To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome.

Design: Multicentre retrospective case-control study.

Setting: 23 hospitals in northern Germany.

Participants: 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome.

Main outcome measures: Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death.

Results: 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P = 0.03), fewer deaths (0% v 5%, p = 0.029), required no abdominal surgery, and excreted E coli for a shorter duration.

Conclusions: Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: doctors from the following 10 centers (Medical School Hannover, Hannover; University Hospital Schleswig Holstein, Lübeck; Evangelic Hospital Gilead, Bielefeld; Bremerhaven Hospital Reinkenheide, Bremerhaven; University Hospital Münster, Münster; Red Cross Hospital Bremen, Bremen; Bremen Hospital-Mitte, Bremen; Hospital Oldenburg, Oldenburg; Diakonissenkrankenhaus Flensburg; Asklepios Clinic Hamburg Barmbek, Hamburg) participated in a single arm multicentre trial, sponsored by Alexion Pharmaceuticals; no support from any organisation for the submitted work; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Therapeutic strategies used by hospitals during outbreak of enterohaemorrhagic Escherichia coli associated haemolytic uraemic syndrome in northern Germany, 2011. Percentage of patients available for present analysis are in brackets
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Fig 2 Onset of symptoms and complications in 11 patients (one patient died on day 68), laboratory results, and diagnosis of haemolytic uraemic syndrome
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Fig 3 Effect of plasmapheresis on platelet counts and levels of lactate dehydrogenase, creatinine, and haemoglobin
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Fig 4 Clinical data in patients with enterohaemorrhagic Escherichia coli induced haemolytic uraemia syndrome treated with or without limited plasmapheresis (3-5 sessions) versus platelet guided plasmapheresis, with plasmapheresis with or without glucocorticoid therapy, and with or without antibiotics
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Fig 5 Platelet counts and levels of lactate dehydrogenase, creatinine, and haemoglobin in 67 patients who were treated with eculizumab and 65 control patients with a similar severity of haemolytic uraemic syndrome
See this image and copyright information in PMC

Comment in

References

    1. Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al. Epidemic profile of shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011;365:1771-80. - PubMed
    1. Robert Koch Institut. Abschließende Darstellung und Bewertung der epidemiologischen Erkenntnisse im EHEC O104:H4 Ausbruch. 2011. [Final report on the epidemiology of the EHEC O104-H4 outbreak, Germany 2011.] www.rki.de/cln_117/nn_205760/DE/Content/InfAZ/E/EHEC/EHEC-Abschlussberic....
    1. Dundas S, Todd WT, Stewart AI, Murdoch PS, Chaudhuri AK, Hutchinson SJ. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis 2001;33:923-31. - PubMed
    1. Wood R, Donaghy M, Dundas S. Monitoring patients in the community with suspected Escherichia coli O157 infection during a large outbreak in Scotland in 1996. Epidemiol Infect 2001;127:413-20. - PMC - PubMed
    1. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005;365:1073-86. - PubMed

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