Treatment of Shiga-Like Toxin--Producing Escherichia coli Infection

To the Editor—The findings of Bennish et al. [1], with regard to a reduction in the frequency of hemolytic uremic syndrome (HUS) among patients who received appropriate antibiotics for Shigella dysenteriae infection, should resurrect interest in designing a prospective antibiotic treatment trial for enterohemorraghic Escherichia coli (EHEC) infection. As the authors detail, Shiga toxin is analogous to one of the common Shiga-like toxins, which are produced by EHEC. Furthermore, there is considerable phylogenetic similarity between E. coli and Shigella species. Both of these factors enhance the theoretical potential that EHEC infections could be benefited by similar treatments, including antimicrobial chemotherapy. As I have previously suggested [2], the choice of antibiotic is critical, because previous studies have shown that, despite in vitro susceptibility, only certain antibiotics are effective for shigellosis [3]. Wong et al. [4] proposed that antibiotics may be a risk factor for progression to HUS during EHEC infection, but the stratification and categorization of antibiotic use would not be consistent with shigellosis treatment trials. A recent meta-analysis from Safdar et al. [5] did not find an increased risk of HUS in EHEC infection. Data from Bell et al. [6] and Proulx et al. [7] also provide similar findings. The latter studies complement those by my colleagues and me [8], in which the safety of certain antibiotics for treatment of E. coli O157:H7 infection was proposed. In other research, we found a possible protective effect of particular antibiotics [9, 10]. Although these studies are not definitive with regard to safety and protection, they, along with the supportive findings of Bennish et al. [1], provide plenty of fuel for hypothesis testing. It is justifiable to propose that an advance in treatment is possible. Caution in the use of antimicrobial chemotherapy is justified, but such caution should not jeopardize the execution of prospective, randomized treatment trials. A choice of ampicillin for the therapeutic trial would be preferable, given the theoretical risk of complicating an evolving nephropathy with a relatively insoluble sulphonamide combination. The treatment group would ideally include children of young age who are at greater risk for progression to HUS and children who are seen early in the course of the illness. The randomized design would necessarily include a preconceived number of patients to achieve sufficient power, but the randomized code and the interim results could be available to an independent oversight group, which would ensure that the study be terminated if preliminary data showed an obvious trend towards adverse effects of antibiotic treatment. The time has come to move forward. Potential conflicts of interest. N.C.: no conflicts.

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