Symptoms and Clinical Course of EHEC O104 Infection in Hospitalized Patients: A Prospective Single Center Study

Objectives Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum β lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany. Methods The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients’ histories, clinical findings, and complications. Results EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated. Conclusions EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as “EAHEC disease”.

[1]  B. Löwe,et al.  Psychological outcome, fatigue, and quality of life after infection with shiga toxin-producing Escherichia coli O104. , 2014, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[2]  H. Frieling,et al.  Psychiatric Symptoms in Patients with Shiga Toxin-Producing E. coli O104:H4 Induced Haemolytic-Uraemic Syndrome , 2014, PloS one.

[3]  Ulrich C. Klostermeier,et al.  Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study , 2012, BMJ : British Medical Journal.

[4]  C. Gerloff,et al.  The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. , 2012, Brain : a journal of neurology.

[5]  H. Karch,et al.  Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  J. Knobloch,et al.  Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. , 2012, JAMA.

[7]  A. Mellmann,et al.  Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain , 2012, Antimicrobial Agents and Chemotherapy.

[8]  A. Flieger,et al.  EHEC/EAEC O104:H4 strain linked with the 2011 German outbreak of haemolytic uremic syndrome enters into the viable but non-culturable state in response to various stresses and resuscitates upon stress relief. , 2011, Environmental microbiology.

[9]  Klaus Stark,et al.  Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. , 2011, The New England journal of medicine.

[10]  A. Mellmann,et al.  Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. , 2011, The Lancet. Infectious diseases.

[11]  S. Faiss,et al.  [Clinical symptoms, treatment and outcome of EHEC and EHEC-HUS patients treated as in-patients]. , 2011, Deutsche medizinische Wochenschrift.

[12]  H. Bangstad,et al.  Clinical aspects of a nationwide epidemic of severe haemolytic uremic syndrome (HUS) in children , 2011, Scandinavian journal of trauma, resuscitation and emergency medicine.

[13]  T. Dallman,et al.  Enteroaggregative E. coli O104 from an outbreak of HUS in Germany 2011, could it happen again? , 2011, Journal of infection in developing countries.

[14]  E. Brzuszkiewicz,et al.  Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC) , 2011, Archives of Microbiology.

[15]  F. Schaefer,et al.  Treatment of typical (enteropathic) hemolytic uremic syndrome. , 2010, Seminars in thrombosis and hemostasis.

[16]  M. Elmaleh,et al.  Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[17]  A. Weiss,et al.  Different Classes of Antibiotics Differentially Influence Shiga Toxin Production , 2010, Antimicrobial Agents and Chemotherapy.

[18]  John Cowden,et al.  Escherichia coli O157 , 2009, BMJ : British Medical Journal.

[19]  J. Craig,et al.  Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[20]  M. Bitzan Treatment options for HUS secondary to Escherichia coli O157:H7. , 2009, Kidney international. Supplement.

[21]  S. Fereshtehnejad,et al.  Short-term and long-term outcome of hemolytic uremic syndrome in Iranian children. , 2008, Journal of nephrology.

[22]  A. Mellmann,et al.  Analysis of Collection of Hemolytic Uremic Syndrome–associated Enterohemorrhagic Escherichia coli , 2008, Emerging infectious diseases.

[23]  S. Vesely,et al.  Sporadic bloody diarrhoea‐associated thrombotic thrombocytopenic purpura‐haemolytic uraemic syndrome: an adult and paediatric comparison , 2008, British journal of haematology.

[24]  C. Walker,et al.  Rifaximin Does Not Induce Toxin Production or Phage-Mediated Lysis of Shiga Toxin-Producing Escherichia coli , 2007, Antimicrobial Agents and Chemotherapy.

[25]  M. Falagas,et al.  Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection? , 2006, Alimentary pharmacology & therapeutics.

[26]  S. Ma,et al.  A Case of Hemolytic Uremic Syndrome Caused by Escherichia coli O104:H4 , 2006, Yonsei medical journal.

[27]  D. Nayar,et al.  Toxic megacolon complicating Escherichia coli O157 infection. , 2006, The Journal of infection.

[28]  Yoshie Tsunomori,et al.  An outbreak of mixed infection of enterohemorrhagic Escherichia coli O26:H11 and norovirus genogroup II at a kindergarten in Shimane, Japan. , 2005, Japanese journal of infectious diseases.

[29]  M. Ciol,et al.  Relative Nephroprotection During Escherichia coli O157:H7 Infections: Association With Intravenous Volume Expansion , 2005, Pediatrics.

[30]  P. Tarr,et al.  Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome , 2005, The Lancet.

[31]  S. Leiz,et al.  CT and MRI in haemolytic uraemic syndrome with central nervous system involvement: distribution of lesions and prognostic value of imaging findings , 2004, Pediatric Radiology.

[32]  A. Garg,et al.  Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. , 2003, JAMA.

[33]  R. Gangnon,et al.  Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. , 2002, JAMA.

[34]  Craig S. Wong,et al.  The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. , 2000, The New England journal of medicine.

[35]  M. Miyazaki,et al.  Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts. , 1999, American journal of epidemiology.

[36]  T. Honda,et al.  Effect of subinhibitory concentrations of antimicrobial agents (quinolones and macrolide) on the production of verotoxin by enterohemorrhagic Escherichia coli O157:H7. , 1999, Canadian journal of microbiology.

[37]  M. Catton,et al.  Combined infection of Norwalk-like virus and verotoxin-producing bacteria associated with a gastroenteritis outbreak. , 1999, Journal of diarrhoeal diseases research.

[38]  G. Gallo,et al.  Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome , 1995, Pediatric Nephrology.

[39]  N. Cimolai,et al.  Risk factors for the central nervous system manifestations of gastroenteritis-associated hemolytic-uremic syndrome. , 1992, Pediatrics.

[40]  G. Delage,et al.  Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. , 1992, The Journal of pediatrics.

[41]  G. Remuzzi,et al.  Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome. , 1992, Journal of the American Society of Nephrology : JASN.

[42]  A. Murphy,et al.  Haemolytic Uraemic Syndrome: 17 Years' Experience in a Scottish Paediatric Renal Unit , 1991, Scottish medical journal.

[43]  J. Estroff,et al.  Neurological Complications of Hemolytic-Uremic Syndrome , 1989, Journal of child neurology.

[44]  B. Rowe,et al.  Haemolytic-uraemic syndrome: clinical experience of an outbreak in the West Midlands. , 1986, British medical journal.

[45]  K. J. Sheth,et al.  Neurological involvement in hemolytic‐uremic syndrome , 1986, Annals of neurology.

[46]  A. Steck,et al.  [Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]. , 1955, Schweizerische medizinische Wochenschrift.

[47]  J. Avorn Eculizumab in Severe Shiga-Toxin-Associated HUS , 2011 .

[48]  T. I. Dolgikh,et al.  [Verotoxin as a major laboratory criterion for Escherichia coli O157-induced enteric infection complicated by hemolytic uremic syndrome in infants in the Omsk region]. , 2010, Klinicheskaia laboratornaia diagnostika.