Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Japan,
Digestion. 2020;101(5):644-650. doi: 10.1159/000501610. Epub 2019 Aug 6.
BACKGROUND/AIMS: Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day -STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls.
Patients in whom eradication treatment using both first- and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009-2011 and 2012-2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-analysis was attempted.
The overall eradication rates, the eradication rate for gyrA mutation negative- and positive- strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones.
Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.
背景/目的:含司他氟沙星(STFX)的方案被证明是幽门螺杆菌三线根除治疗的有效选择。据报道,全球范围内对喹诺酮类药物的耐药性也在增加。因此,我们分析了目前含 10 天 STFX 的三线补救治疗的疗效,以及与 2 个历史对照相比,幽门螺杆菌对抗生素耐药性的变化。
2014 年至 2015 年,我们从使用一线和二线三联疗法根除治疗失败的患者中招募了患者。在治疗前确定 STFX、克拉霉素(CLR)、阿莫西林(AMX)、甲硝唑(MTZ)的最低抑菌浓度和幽门螺杆菌菌株的 gyrA 突变状态。之后,患者接受了为期 10 天的三联疗法,包括埃索美拉唑(20mg,每日 2 次)、AMX(500mg,每日 4 次)和 STFX(100mg,每日 2 次;10 天 EAS)。与 2009-2011 年和 2012-2013 年的 2 项关于含 STFX 的三线补救治疗的先前报告相比,比较了根除率和幽门螺杆菌对抗生素的耐药率。为了探讨含 STFX、AMX 和质子泵抑制剂的方案的根除率与 gyrA 突变或 AMX 耐药的位置之间的关系,我们尝试了一项荟萃分析。
总的根除率、gyrA 突变阴性和阳性菌株的根除率分别为 81.6%(31/38)、94.7%(18/19)和 68.4%(13/19)。这些比率与前 2 项报告没有显著差异。STFX、CLR、AMX、MTZ 的耐药率分别为 50.0%、81.6%、36.8%、78.9%和 50.0%,与前 2 项报告也无显著差异。荟萃分析显示,gyrA 突变阴性菌株的根除失败风险明显低于 gyrA 突变阳性菌株,gyrA 突变位于 D91 的根除失败风险明显低于 gyrA 突变位于 N87(p<0.001 和 p=0.022,分别)。此外,荟萃分析显示,AMX 敏感菌株的根除失败风险明显低于 AMX 耐药菌株。
从 2009 年到 2015 年,幽门螺杆菌对抗生素耐药性的变化没有观察到。gyrA 突变状态是 STFX/AMX 三联方案作为三线补救治疗成功根除的更好预测标志物。