Department of Microbiology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Ann Clin Microbiol Antimicrob. 2011 Sep 12;10:34. doi: 10.1186/1476-0711-10-34.
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.
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.
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.
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.
由于与潜在致命后遗症相关，使用抗菌药物治疗大肠杆菌 O157:H7 感染存在争议。志贺毒素的产生被认为是该细菌发病机制的核心。因此，在细菌根除之前，减少这些毒素的表达可能提供更安全的治疗过程。
我们通过实时逆转录聚合酶链反应评估了在体外使用利福平降低大肠杆菌 O157:H7 中的志贺毒素基因表达，然后用庆大霉素进行细菌根除，以评估其效果。通过反向被动乳胶凝集法检测处理后的细菌细胞中毒素的释放。还监测了这种治疗方法对感染大肠杆菌 O157:H7 的 BALB/c 小鼠生存的影响。
与单独用庆大霉素处理相比，用利福平的最低抑菌浓度 (MIC) 处理大肠杆菌 O157:H7 后再用庆大霉素的最低杀菌浓度 (MBC) 处理可使编码志贺毒素的基因转录显著降低（>99% 的降低）。与单独用庆大霉素处理相比，用利福平 MIC 孵育后再加入庆大霉素 MBC 也可减少志贺毒素从大肠杆菌 O157:H7 的释放。另一方面，在用大肠杆菌 O157:H7 感染的 BALB/c 小鼠中，用体内 MIC 等效剂量的利福平治疗后再用体内 MBC 等效剂量的庆大霉素治疗，观察到最高的存活率，与单独用庆大霉素或利福平治疗的小鼠相比。
在治疗大肠杆菌 O157:H7 感染时，在使用杀菌药物之前使用非致死性表达抑制剂量的抗菌药物是有效的，并且除了其他产志贺毒素的大肠杆菌菌株外，对人类感染这种病原体也可能有用。
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