Mégraud F, Occhialini A, Rossignol J F
Laboratoire de Bactériologie, Hôpital Pellegrin, 33076 Bordeaux Cedex, France.
Antimicrob Agents Chemother. 1998 Nov;42(11):2836-40. doi: 10.1128/AAC.42.11.2836.
Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tizoxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of Helicobacter pylori infection may be jeopardized by metronidazole resistance, nitazoxanide and tizoxanide were tested in vitro against these bacteria. The MICs of these two compounds were determined by agar dilution and were compared to those of metronidazole. Exposure to subinhibitory concentrations of nitazoxanide was also carried out by the method of Szybalski (W. Szybalski and V. Bryson, J. Bacteriol. 64:489-499, 1952). The MICs of nitazoxanide and tizoxanide for 103 strains ranged from 0.25 to 8 microg/ml, with the MIC at which 50% of strains are inhibited (MIC50) being 1 microg/ml and the MIC90 being 4 microg/ml, and no resistant strain was detected, whereas strains resistant to metronidazole were detected. When 10 strains were successively subcultured on medium containing nitazoxanide, no significant change in the MICs of this compound was observed. A pilot study of nitazoxanide for the treatment of H. pylori infection was carried out with 86 patients in association with 20 mg of omeprazole. An eradication rate of 83% (95% confidence interval, 64% to 94%) was obtained in a per-protocol analysis in the group receiving 1 g of nitazoxanide orally twice daily, and a few side effects were observed. The failures could not be explained by the selection of resistant strains since the MICs of nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplified polymorphic DNA analysis in four cases) cultured before and after the treatment failure. Nitazoxanide exhibits good antimicrobial activity against H. pylori without the problem of acquired resistance which is encountered with metronidazole and has been demonstrated to have a satisfactory effect in a dose-ranging pilot study. It is therefore a good candidate to be included in treatment regimens aimed at the eradication of H. pylori.
硝唑尼特是一种噻唑啉酮化合物，其去乙酰基衍生物替唑尼特对厌氧菌、蠕虫和原生动物均具有抗菌特性。由于甲硝唑耐药性可能会影响幽门螺杆菌感染的治疗效果，因此对硝唑尼特和替唑尼特进行了体外抗幽门螺杆菌测试。采用琼脂稀释法测定了这两种化合物的最低抑菌浓度（MIC），并与甲硝唑的MIC进行了比较。同时，还采用斯兹巴尔斯基方法（W. Szybalski和V. Bryson，《细菌学杂志》64:489 - 499，1952年）对硝唑尼特的亚抑菌浓度进行了检测。硝唑尼特和替唑尼特对103株菌株的MIC范围为0.25至8μg/ml，50%菌株被抑制时的MIC（MIC50）为1μg/ml，MIC90为4μg/ml，未检测到耐药菌株，而检测到了对甲硝唑耐药的菌株。当10株菌株在含有硝唑尼特的培养基上连续传代培养时，该化合物的MIC未观察到明显变化。对86例患者联合20mg奥美拉唑进行了硝唑尼特治疗幽门螺杆菌感染的初步研究。在每日口服2次1g硝唑尼特的治疗组中，按符合方案分析得出根除率为83%（95%置信区间为64%至94%），且观察到少数副作用。治疗失败不能用耐药菌株的选择来解释，因为治疗失败前后培养的6对分离株（4例经随机扩增多态性DNA分析证实为同一菌株）的硝唑尼特MIC相似。硝唑尼特对幽门螺杆菌具有良好的抗菌活性，不存在甲硝唑所面临的获得性耐药问题，并且在剂量范围初步研究中已证明具有满意的效果。因此，它是根除幽门螺杆菌治疗方案中的一个良好候选药物。
