title: Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157:H7 in mice with protein-calorie malnutrition.
abstract: Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected 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 Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.
authors.affiliation: Department of Bacteriology, Nara Medical University, Kashihara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kurioka
authors.forename: Y
authors.initials: Y
authors.lastname: Yunou
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: E
authors.initials: E
authors.lastname: Kita
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001427:Bacterial Toxins / Q000032:analysis / Q000096:biosynthesis; D001923:Brain Chemistry; D004195:Disease Models, Animal; D018450:Disease Progression; D004927:Escherichia coli Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D019453:Escherichia coli O157 / Q000187:drug effects*; D005243:Feces / Q000737:chemistry; D005578:Fosfomycin / Q000008:administration & dosage; D007612:Kanamycin / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009643:Norfloxacin / Q000008:administration & dosage; D011502:Protein-Energy Malnutrition / Q000150:complications*; D012016:Reference Values; D012680:Sensitivity and Specificity; D022603:Shiga Toxins; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D022603:Shiga Toxins; D005578:Fosfomycin; D007612:Kanamycin; D000667:Ampicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D009643:Norfloxacin