Departmentsof Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan.
Antimicrob Agents Chemother. 2011 Mar;55(3):1123-9. doi: 10.1128/AAC.01131-10. Epub 2010 Dec 28.
The accuracy of genotypic resistance to levofloxacin (gyrA mutations) and its agreement with treatment outcomes after levofloxacin-based therapy have not been reported. We aimed to assess the correlation. Helicobacter pylori strains isolated from patients who received levofloxacin-based and clarithromycin-based triple therapies in a previous randomized trial were analyzed for point mutations in gyrA and 23S rRNA. PCR followed by direct sequencing was used to assess the gyrA and 23S rRNA mutations. An agar dilution test was used to determine the MICs of clarithromycin and levofloxacin. We found that the agreement between genotypic and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1 μg/ml (kappa coefficient, 0.754). The eradication rates in patients with and without gyrA mutations were 41.7% and 82.7%, respectively (P = 0.003). The agreement between genotypic and phenotypic resistance to clarithromycin was best when the MIC breakpoint was >2 μg/ml (kappa, 0.694). The eradication rates in patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (P < 0.001). The agreements (kappa coefficient) between therapeutic outcomes after clarithromycin-based triple therapy and genotypic and phenotypic resistance were 0.671 and 0.356, respectively. The agreements (kappa coefficient) between therapeutic outcomes after levofloxacin-based triple therapy and genotypic and phenotypic resistance were 0.244 and 0.190, respectively. In conclusion, gyrA and 23S rRNA mutations in H. pylori strains appeared to be better markers than phenotypic resistance in the prediction of treatment outcomes. The optimal breakpoints for levofloxacin and clarithromycin resistance appeared to be >1 μg/ml and >2 μg/ml, respectively.
对左氧氟沙星（gyrA 突变）的基因型耐药的准确性及其与左氧氟沙星为基础的治疗后结果的一致性尚未报道。我们旨在评估相关性。从以前的随机试验中接受左氧氟沙星和克拉霉素三联疗法的患者中分离出幽门螺杆菌菌株，用于分析 gyrA 和 23S rRNA 中的点突变。PCR 后直接测序用于评估 gyrA 和 23S rRNA 突变。琼脂稀释试验用于确定克拉霉素和左氧氟沙星的 MIC。我们发现，当 MIC 临界点>1μg/ml 时，基因型和表型对左氧氟沙星的耐药性之间的一致性最佳（kappa 系数，0.754）。有和没有 gyrA 突变的患者的根除率分别为 41.7%和 82.7%（P=0.003）。当 MIC 临界点>2μg/ml 时，基因型和表型对克拉霉素的耐药性之间的一致性最佳（kappa，0.694）。有和没有 23S rRNA 突变的患者的根除率分别为 7.7%和 93.5%（P<0.001）。克拉霉素三联疗法后治疗结果与基因型和表型耐药之间的一致性（kappa 系数）分别为 0.671 和 0.356。左氧氟沙星三联疗法后治疗结果与基因型和表型耐药之间的一致性（kappa 系数）分别为 0.244 和 0.190。总之，幽门螺杆菌菌株中的 gyrA 和 23S rRNA 突变似乎比表型耐药更能预测治疗结果。左氧氟沙星和克拉霉素耐药的最佳临界点分别为>1μg/ml 和>2μg/ml。
