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Background  Treatment of  Escherichia coli  O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy.    Methods  The utility of decreasing Shiga toxin gene expression in  E. coli  O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated  in vitro  using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of  E. coli  O157:H7-infected BALB/c mice was also monitored.    Results  Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating  E. coli  O157:H7  in vitro  with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from  E. coli  O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with  E. coli  O157:H7 was observed in those treated with the  in vivo  MIC equivalent dose of rifampicin followed by the  in vivo  MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.    Conclusions  The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating  E. coli  O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing  E. coli  strains.

annals of clinical microbiology and antimicrobials

Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice