Jenks P J, Ferrero R L, Tankovic J, Thiberge J M, Labigne A
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 75724 Paris Cedex 15, France.
Antimicrob Agents Chemother. 2000 Oct;44(10):2623-9. doi: 10.1128/AAC.44.10.2623-2629.2000.
The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 microg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P < or =0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P < or =0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice.
本研究的主要目的是确定幽门螺杆菌rdxA基因编码的硝基还原酶是否负责呋喃妥因的还原激活，以及含呋喃妥因的三联疗法能否根除小鼠体内对甲硝唑敏感和耐药的幽门螺杆菌感染。通过琼脂稀释法测定MIC，评估了亲本和同基因rdxA突变株（三对）以及从小鼠（30株）和患者（20株）中分离出的一系列配对的甲硝唑敏感和耐药菌株对呋喃妥因的敏感性。用甲硝唑或呋喃妥因作为三联疗法的一部分，对定植有甲硝唑敏感的幽门螺杆菌SS1菌株或甲硝唑耐药的rdxA SS1突变株的小鼠组进行治疗。治疗完成后1个月，处死小鼠并对其胃进行幽门螺杆菌培养。所有测试菌株的呋喃妥因MIC在0.5至4.0μg/ml之间。亲本菌株与各自的rdxA突变株对呋喃妥因的敏感性之间，或配对的甲硝唑敏感和耐药幽门螺杆菌分离株之间，均无显著差异。甲硝唑治疗方案根除了所有8只感染SS1的小鼠以及8只接种rdxA突变株的小鼠中的1只的感染（P≤0.001）。呋喃妥因治疗方案未能根除6只感染SS1的小鼠中的任何一只的感染（P≤0.001），并清除了7只接种rdxA突变株的小鼠中的1只的感染。这些结果表明，尽管呋喃妥因在体外对幽门螺杆菌具有良好的活性，且甲硝唑与呋喃妥因之间不存在交叉耐药性，但含呋喃妥因的根除方案无法根除小鼠体内对甲硝唑敏感或耐药的幽门螺杆菌感染。
