Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157 : H7 in mice with protein-calorie malnutrition

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia col i O157.H7 is controversial because of the possibility of its inducing hemol ytic uremic syndrome and acute encephalopathy. In a previous study, mice wi th protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice inf ected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Sh iga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fo sfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethox azole for 3 days: mice on protocol A received the antibiotic on days 1-3, s tarting on the day after infection, and mice on protocol B received the ant ibiotic on days 3-5. The duration of fecal pathogen excretion was shorter a nd the toxin level in the stool and blood lower in the mice that received p rotocol A than in untreated mice; all of the mice treated on protocol A sur vived the lethal infection. All antibiotics except trimethoprim-sulfamethox azole, administered on protocol B, exhibited the same effect as that exhibi ted by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxatole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. Th ese results suggest that the antibiotics used in this study, except for tri methoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndr ome and acute encephalopathy following Escherichia coli O157:H7 infection i n humans, and that fosfomycin, in particular, may be relevant for testing i n humans.