Background: Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an\r\nassociation with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the\r\npathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication\r\nmay provide a safer course of therapy.\r\nMethods: The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial\r\neradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction.\r\nToxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this\r\ntreatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored.\r\nResults: Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:\r\nH7 in vitro with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal\r\nconcentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease).\r\nThe release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC\r\nof gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli\r\nO157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC\r\nequivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.\r\nConclusions: The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in\r\ntreating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in\r\naddition to other Shiga toxin producing E. coli strains.
Loading....