Potential therapeutic agents for the prevention and treatment of haemolytic uraemic syndrome in shiga toxin producing Escherichia coli infection.

PURPOSE OF REVIEW: Shiga toxin producing Escherichia coli (STEC) cause a wide spectrum of disease ranging from asymptomatic carriage through to haemorrhagic colitis and the haemolytic uraemic syndrome. There are no current therapeutic interventions available in clinical practice that can prevent the development of haemolytic uraemic syndrome. A number of newly developed agents offer the potential for the treatment of STEC-associated disease. RECENT FINDINGS: Three different classes of agent designed to bind and inactivate shiga toxin have now been developed. Synthetic toxin binders, recombinant bacteria and monoclonal antibodies provide potentially potent agents that could prevent the development of haemolytic uraemic syndrome. These agents have been shown in animal models of STEC disease to be effective. A recent clinical trial of one synthetic toxin binder showed no benefit in established haemolytic uraemic syndrome. More potent toxin binders, however, have since been developed and await human clinical trials. It is likely to be important that these agents are administered early in the course of disease in order to have maximum efficacy. Although rapid diagnostic techniques are available for the diagnosis of STEC disease, they still rely on stool culture. SUMMARY: Clinicians need to maintain a high level of suspicion of STEC disease as the diagnosis is often made on epidemiological and clinical grounds. This will allow potential cases to be identified early and treated appropriately.

Blood group and susceptibility to disease caused by Escherichia coli O157.

Patients (n=186) infected during the Escherichia coli O157 outbreak in Scotland in 1996 were assessed for blood group markers (ABO, Lewis, and P) associated with other gastrointestinal infections. Binding of bacteria to epithelial cells was assessed by flow cytometry. Buffy coats from blood donors were examined for inflammatory responses to culture filtrates of the outbreak strain. Individuals of blood group O comprised 63.4% of patients, compared with 53.4% (P <.05) and 53.9% (P <.01) of neighboring populations in Airdrie and Glasgow, respectively; group O also comprised 64.3% of patients with hemolytic uremic syndrome (HUS) and 87.5% of patients who died (P <.05). No or weak agglutination by anti-P antiserum was observed for 40.7% of control persons (n=122), 61.5% of all patients (P =.0027), and 83.3% of patients with HUS (P =.013). The susceptibility of group O to E. coli was not associated with increased binding of bacteria to epithelial cells or with higher production of tumor necrosis factor (TNF)-alpha or interleukin-6. Leukocytes of P-negative blood donors produced higher levels of TNF-alpha than those of P-positive donors.