Infection at the time of the recent outbreak in Germany. As only 1379592 hospitalized 842-07-9 biological activity patients were analysed, our results do not reflect the full spectrum of the epidemiology. The observed patient characteristics, symptoms, and complications differ from earlier reports EHEC outbreaks, which focused predominantly on EHEC O157:H7 infections [28?4]. In accordance with the first epidemiologic analysis [4,35] our data confirm young adult female patients to be the largest group affected by the 2011 EHEC-induced disease in Germany (61 ). Early symptoms are comparable to the onset of EHEC 0157 infections [29]. The most 1454585-06-8 site common symptom leading to hospital admission was bloody diarrhoea. HUS represents the most frequent (59 ) and severe complication, a conclusion consistent with results of the first epidemiologic analysis [4]. This differs markedly from the reported incidence of 10?5 HUS in EHEC 0157 infections [28]. Severe neurological manifestations occurred in many patients (43 ) and coincided with HUS in most cases. Reports of EHEC 
0157 infections described neurological complications in 30 of HUS patients [30?2,36,37] with comparable manifestations, but mainly in children [38]. We also observed severe neurological complications in non-HUS patients (3/26). The sudden onset and the severity of neurological symptoms require intensive observation to ensure adequate treatment. Complications can develop independently from diarrhoea, as found in 17/36 (47 ) HUS patients. Rapid stagnation of bowel movements seemed to indicate the development of complications. In many cases the time gap between cessation of diarrhoea and onset of complications was either misleadingly long (up to 6 days), or complications developed within hours and resulted in the immediate need for intensive care. These observations prompted us to adapt our care in terms of an intensified monitoring at frequent intervals (“Altona EAHEC Monitoring Standard”; Table 3). Search for manifestations of thrombotic microangiopathy should contribute to early detection of complications before they become clinically evident e.g. cardiac arrhythmia. This approach, including an extensive fluid-management, may have helped to keep mortality in our cohort (3 of HUS patients) below rates reported earlier (9 ) [33,34]. In contrast to earlier reports [17,28] we could not observe any case of deterioration attributable to antibiotic treatment. A recent publication on the use of Azithromycin in EHEC O104:H4 infection found no increase in frequency of HUS or worsening of EHEC related symptoms. Treatment with Azithromycin was correlated with a shorter time of EHEC colonisation [15]. In vitro data indicate different effects on Shiga-toxin production depending on the antibiotic agent used: Ciprofloxacin induces Shiga-toxin production while Meropenem, Azithromycin, Tigecyline, and Rifaximin do not influence Shigatoxin production [39]. Because of the limited number of patients, statistical analysis of the effectiveness of therapeutic procedures as plasma-separation, treatment with Eculizumab, and antibiotic treatment withFigure 5. Development of serum creatinine, LDH, and thrombocytes in 36 patient suffering from HUS. [range, 25th?5th percentiles, median, reference levels]. doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsFigure 6. Complications in 61 patients with EHEC O104 infection. cum: cumulative; other neurological symptoms include: 
cortical blindness (n = 3) and choreatic syndrome.Infection at the time of the recent outbreak in Germany. As only 1379592 hospitalized patients were analysed, our results do not reflect the full spectrum of the epidemiology. The observed patient characteristics, symptoms, and complications differ from earlier reports EHEC outbreaks, which focused predominantly on EHEC O157:H7 infections [28?4]. In accordance with the first epidemiologic analysis [4,35] our data confirm young adult female patients to be the largest group affected by the 2011 EHEC-induced disease in Germany (61 ). Early symptoms are comparable to the onset of EHEC 0157 infections [29]. The most common symptom leading to hospital admission was bloody diarrhoea. HUS represents the most frequent (59 ) and severe complication, a conclusion consistent with results of the first epidemiologic analysis [4]. This differs markedly from the reported incidence of 10?5 HUS in EHEC 0157 infections [28]. Severe neurological manifestations occurred in many patients (43 ) and coincided with HUS in most cases. Reports of EHEC 0157 infections described neurological complications in 30 of HUS patients [30?2,36,37] with comparable manifestations, but mainly in children [38]. We also observed severe neurological complications in non-HUS patients (3/26). The sudden onset and the severity of neurological symptoms require intensive observation to ensure adequate treatment. Complications can develop independently from diarrhoea, as found in 17/36 (47 ) HUS patients. Rapid stagnation of bowel movements seemed to indicate the development of complications. In many cases the time gap between cessation of diarrhoea and onset of complications was either misleadingly long (up to 6 days), or complications developed within hours and resulted in the immediate need for intensive care. These observations prompted us to adapt our care in terms of an intensified monitoring at frequent intervals (“Altona EAHEC Monitoring Standard”; Table 3). Search for manifestations of thrombotic microangiopathy should contribute to early detection of complications before they become clinically evident e.g. cardiac arrhythmia. This approach, including an extensive fluid-management, may have helped to keep mortality in our cohort (3 of HUS patients) below rates reported earlier (9 ) [33,34]. In contrast to earlier reports [17,28] we could not observe any case of deterioration attributable to antibiotic treatment. A recent publication on the use of Azithromycin in EHEC O104:H4 infection found no increase in frequency of HUS or worsening of EHEC related symptoms. Treatment with Azithromycin was correlated with a shorter time of EHEC colonisation [15]. In vitro data indicate different effects on Shiga-toxin production depending on the antibiotic agent used: Ciprofloxacin induces Shiga-toxin production while Meropenem, Azithromycin, Tigecyline, and Rifaximin do not influence Shigatoxin production [39]. Because of the limited number of patients, statistical analysis of the effectiveness of therapeutic procedures as plasma-separation, treatment with Eculizumab, and antibiotic treatment withFigure 5. Development of serum creatinine, LDH, and thrombocytes in 36 patient suffering from HUS. [range, 25th?5th percentiles, median, reference levels]. doi:10.1371/journal.pone.0055278.gEHEC O104 Infection in Hospitalized PatientsFigure 6. Complications in 61 patients with EHEC O104 infection. cum: cumulative; other neurological symptoms include: cortical blindness (n = 3) and choreatic syndrome.
