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首页> 外文期刊>Chemotherapy: International Journal of Experimental and Clinical Chemotherapy >In vitro activity of rifaximin, metronidazole and vancomycin against Clostridium difficile and the rate of selection of spontaneously resistant mutants against representative anaerobic and aerobic bacteria, including ammonia-producing species.
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In vitro activity of rifaximin, metronidazole and vancomycin against Clostridium difficile and the rate of selection of spontaneously resistant mutants against representative anaerobic and aerobic bacteria, including ammonia-producing species.

机译：利福昔明，甲硝唑和万古霉素对艰难梭菌的体外活性以及针对代表性厌氧和好氧细菌（包括产氨菌）的自发抗性突变体的选择率。

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BACKGROUND: Rifaximin is a rifamycin derivative characterized by a wide antibacterial activity. This drug is neither absorbed by the gastrointestinal tract nor inactivated by gastric juices, and exerts its action entirely within the intestinal lumen. METHODS: In this study, the activity of this antibiotic was compared with that of metronidazole and vancomycin against 93 Clostridium difficile isolates. The rate of emergence of bacteria spontaneously resistant to the new compound was also evaluated in relation to representative gram-positive and gram-negative strains. In terms of MIC(50) values, rifaximin showed an intrinsic activity superior to that of the other agents. The emergence of spontaneously resistant strains was assessed with 46 aerobic (staphylococci, enterococci, Proteus spp., Citrobacter freundii, Providencia rettgeri, enteropathogenic, enteroinvasive, enterotoxigenic and entero- hemorrhagic Escherichia coli, and Salmonella enteritidis) and anaerobic (Clostridium spp., Bacteroides spp., Fusobacterium nucleatum and Peptococcus spp.) pathogens, most of them also ammonium producers. Two different methods, broth and agar dilution, were employed. RESULTS: When liquid medium was employed, bacteria capable of sustained growth in 100 microg/ml of rifaximin were obtained after 2-5 transfers with gram-positive aerobic cocci, 2-3 transfers with gram-negative aerobic strains and 2-5 transfers with anaerobic species. At the highest dose used with the agar dilution method (8 x MIC), the frequency of emergence of spontaneously resistant mutants ranged from <1 x 10(-9) to 1.6 x 10(-8) with gram-positive aerobic and anaerobic cocci, while with aerobic and anaerobic gram-negative bacteria, this value ranged from <1 x 10(-9) to 1.7 x 10(-7). C. difficile showed a particularly low incidence of spontaneously resistant mutants (<1 x 10(-9)). The low incidence of resistant subpopulations selected by levels of 8 x MIC of rifaximin suggests that the high levels of the drug which were reached in the gastrointestinal lumen may further prevent the selection of mutants. CONCLUSION: The low toxicity, broad antibacterial activity and very poor absorption from the gastrointestinal tract of rifaximin suggest a potential therapeutic use for this drug in gastrointestinal diseases, as well as in the management of patients with cirrhosis and chronic portal-systemic encephalopathy. Copyright 2000 S. Karger AG, Basel
机译：背景：利福昔明是一种利福霉素衍生物，具有广泛的抗菌活性。该药物既不被胃肠道吸收也不被胃液灭活，并且完全在肠腔内发挥作用。方法：本研究将这种抗生素与甲硝唑和万古霉素对93株艰难梭菌分离物的活性进行了比较。还针对代表性的革兰氏阳性和革兰氏阴性菌株评估了对新化合物自发耐药的细菌的出现速度。就MIC（50）值而言，利福昔明表现出的内在活性优于其他药物。用46种需氧菌（葡萄球菌，肠球菌，变形杆菌，弗氏柠檬酸杆菌，普罗维登斯氏菌，肠致病性，肠侵袭性，产肠毒素性和肠出血性大肠埃希氏菌和肠炎沙门氏菌）评估了自发耐药菌株的出现。菌，核梭菌和链球菌）病原体，其中大多数也是铵生产者。采用两种不同的方法，肉汤和琼脂稀释。结果：当使用液体培养基时，用革兰氏阳性需氧球菌2-5次转移，用革兰氏阴性需氧菌2-3次转移和用革兰氏阴性需氧菌株2-5次转移后，在100μg/ ml的利福昔明中能够持续生长的细菌。厌氧菌种。在琼脂稀释法使用的最高剂量下（8 x MIC），具有革兰氏阳性需氧和厌氧球菌的自发抗性突变体的出现频率范围从<1 x 10（-9）到1.6 x 10（-8）。 ，而对于需氧和厌氧革兰氏阴性细菌，该值的范围从<1 x 10（-9）到1.7 x 10（-7）。艰难梭菌显示自发抗性突变体的发生率特别低（<1 x 10（-9））。通过利福昔明的8 x MIC水平选择的耐药亚群发生率低，这表明在胃肠道内腔中达到的高水平药物可能进一步阻止了突变体的选择。结论：利福昔明的低毒性，广泛的抗菌活性和从胃肠道的吸收非常差，表明该药在胃肠道疾病以及肝硬化和慢性门脉系统性脑病患者的治疗中具有潜在的治疗用途。版权所有2000 S. Karger AG，巴塞尔

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