Risk Factors for Development of Hemolytic Uremic Syndrome in a Cohort of Adult Patients with STEC 0104:H4 Infection

Alexander Zoufaly,Katharina Fraedrich,Tim Magnus,Sabine Jordan,Christoph Rüther,Christine Neumann-Grutzeck,Martin Nitschke,Karl Wegscheider,Stefan Schmiedel,Jakob P Cramer,Friedhelm Sayk,Klaus Fellermann,Andreas De Weerth,Eik Vettorazzi,Ansgar W Lohse,Irmtraut Koop,Niels H Asselborn,Jan Phillip Bremer ,R Stahl

doi:10.1371/journal.pone.0059209

Abstract

The outbreak of Shiga toxin producing E.coli O104:H4 in northern Germany in 2011 was one of the largest worldwide and involved mainly adults. Post-diarrheal hemolytic uremic syndrome (HUS) occurred in 22% of STEC positive patients. This study’s aim was to assess risk factors for HUS in STEC-infected patients and to develop a score from routine hospital parameters to estimate patient risks for developing HUS. In a cohort analysis, adult patients with STEC infection were included in five participating hospitals in northern Germany between May and July 2011. Clinical data were obtained from questionnaires and medical records, laboratory data were extracted from hospitals’ electronic data systems. HUS was defined as thrombocytopenia, hemolytic anemia and acute renal dysfunction. Random forests and multivariate logistic regression were used to identify risk factors for HUS and develop a score using the estimated coefficients as weights. Among 259 adults with STEC infection, vomiting (OR 3.48,95%CI 1.88–6.53), visible blood in stools (OR 3.91,95%CI1.20–16.01), age above 75 years (OR 3.27, 95%CI 1.12–9.70) and elevated leukocyte counts (OR 1.20, 95%CI 1.10–1.31, per 1000 cells/mm3) were identified as independent risk factors for HUS. A score using these variables has an area under the ROC curve of 0.74 (95%CI 0.68–0.80). Vomiting, visible blood in stools, higher leukocyte counts, and higher age indicate increased risk for developing HUS. A score using these variables might help to identify high risk patients who potentially benefit from aggressive pre-emptive treatment to prevent or mitigate the devastating consequences of HUS.

Highlights

The hemolytic uremic syndrome (HUS) is a serious and potentially life-threatening complication in infections with Shiga toxin-producing Escherichia coli (STEC) [1,2]
Informed consent was provided by 315 patients, 67 patients were excluded for missing laboratory tests or presence of HUS at first contact or the fact that they were referred with known STEC infection from other hospitals for specific treatment of suspected HUS
We identified vomiting, elevated leukocyte counts, age .75years, and presence of visible blood in stools as independent risk factors for the development of HUS in adults infected with the novel E.coli STEC O104:H4 strain

Summary

Introduction

The hemolytic uremic syndrome (HUS) is a serious and potentially life-threatening complication in infections with Shiga toxin-producing Escherichia coli (STEC) [1,2]. During the outbreak with this novel strain, patients with symptoms of uncomplicated colitis and proven STEC infection were followed daily mostly as inpatients at secondary and tertiary health care centers until complete recovery or the onset of HUS and other complications. This close follow-up was mandatory due to the lack of established prognostic markers and risk factors. This task is associated with massive impact on both, patients and health care workers and causes high costs [12]. As currently no causal therapy for established HUS exists, early identification of patients with STEC infection at high risk for complications is essential for the provision of pre-emptive treatment to prevent development of HUS and to facilitate the clinical management

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