Therapeutic effect of fosfomycin against interstinal infection with Escherichia coli O157: H7 in a mouse model

I. Kobayashi, H. Muraoka, K. Matsuzaki, T. Saika, M. Nishida, H. Akita, S. Iwata, Y. Sato, K. Sunakawa

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Abstract

The therapeutic effect of fosfomycin at a large oral dose against intestinal infection with Escherichia coli O157: H7 was investigated in a mouse model previously described. Three ICR strain (IQI, germ free) mice aged 5 weeks were challenged orally with a verotoxin-producing strain NK2 of E. coli O157: H7. The high levels of viable cells, 3.0 x 1010-3.4 x 108 CFU/g, were excreted into the feces of the untreated mice for 3-10 days after bacterial challenge. Fosfomycin was given at an oral dose of 600 mg/kg twice a day for 6 days to 3 mice infected with E. coli O157: H7, beginning 3 days after the challenge, to investigate changes in viable cell counts and to measure fecal concentrations of fosfomycin. Results were that the viable cells decreased markedly, (from about 1010 CFU/g before dosing) to 103- 104 CFU/g on day 1 of dosing, and no viable cells were detected in the feces from day 2 of dosing onwards. During the period, no verotoxin was detected in fecal samples collected from all 6 test mice (including 3 control mice). Concentrations of fosfomycin in the feces after dosing were 34.6-47.4 μg/g in all the mice on day i of dosing, and 62.4 and 131.1 μg/g in 2 of the mice on day 6 after dosing, but nondetectable otherwise. These results suggested that a marked decrease in viable cells without the liberation of verotoxin was observed in the feces of infected mice after fosfomycin was given orally in a massive dose.

Original languageEnglish
Pages (from-to)445-449
Number of pages5
JournalJapanese Journal of Chemotherapy
Volume46
Issue number11
Publication statusPublished - 1998 Dec 1

Keywords

  • E. coli O 157: H7
  • Fosfomycin
  • Mouse Infection
  • Verotoxin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Kobayashi, I., Muraoka, H., Matsuzaki, K., Saika, T., Nishida, M., Akita, H., Iwata, S., Sato, Y., & Sunakawa, K. (1998). Therapeutic effect of fosfomycin against interstinal infection with Escherichia coli O157: H7 in a mouse model. Japanese Journal of Chemotherapy, 46(11), 445-449.