Yamamoto Y, Hakki A, Friedman H, Okubo S, Shimamura T, Hoffman P S, Rossignol J
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Fla. 33612, USA.
Chemotherapy. 1999 Jul-Aug;45(4):303-12. doi: 10.1159/000007200.
Nitazoxanide (NTZ), a synthesized drug of the nitrothiazolide class, was initially developed as an antiparasitic compound. This compound has recently been shown to have antibacterial activities against some bacterial pathogens. In the present study, NTZ and its main metabolite tizoxanide (TIZ) were found to have strong minimum inhibitory concentrations (MICs) against both metronidazole (MTZ)-resistant strains and sensitive clinical isolates of Helicobacter pylori. The MIC90 of both NTZ and TIZ against 37 clinical isolates was 8 microg/ml. Vacuolating toxin activity of H. pylori assayed by HeLa cell vacuole formation was inhibited by NTZ at a sub-MIC. In contrast, urease production by H. pylori was not specifically affected by the sub-MIC of NTZ. An acidic pH (pH 5.0) medium reduced the antimicrobial activity of the drug in terms of growth inhibition due to the low growth rate of the bacteria, but killing activity of NTZ against the bacteria was still observed. Thus, it was apparent that both NTZ and TIZ are highly effective against H. pylori, even when the bacteria are resistant to MTZ.
硝唑尼特(NTZ)是一种硝基噻唑类合成药物,最初作为抗寄生虫化合物开发。最近发现该化合物对一些细菌病原体具有抗菌活性。在本研究中,发现硝唑尼特及其主要代谢产物替唑尼特(TIZ)对甲硝唑(MTZ)耐药菌株和幽门螺杆菌敏感临床分离株均具有很强的最低抑菌浓度(MIC)。硝唑尼特和替唑尼特对37株临床分离株的MIC90均为8微克/毫升。通过HeLa细胞液泡形成测定的幽门螺杆菌空泡毒素活性在低于MIC时被硝唑尼特抑制。相比之下,幽门螺杆菌脲酶的产生不受硝唑尼特低于MIC的特异性影响。酸性pH(pH 5.0)培养基由于细菌生长速率低,在生长抑制方面降低了药物的抗菌活性,但仍观察到硝唑尼特对细菌的杀伤活性。因此,很明显,即使细菌对甲硝唑耐药,硝唑尼特和替唑尼特对幽门螺杆菌也非常有效。