Chuah Seng-Kee, Liang Chih-Ming, Lee Chen-Hsiang, Chiou Shue-Shian, Chiu Yi-Chun, Hu Ming-Luen, Wu Keng-Liang, Lu Lung-Sheng, Chou Yeh-Pin, Chang Kuo-Chin, Kuo Chung-Huang, Kuo Chung-Mou, Hu Tsung-Hui, Tai Wei-Chen
From the Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital (S-KC, C-ML, S-SC, Y-CC, M- LH, K-LW, L-SL, Y-PC, K-CC, C-HK, C-MK, T-HH, W-CT); Chang Gung University, College of Medicine, Kaohsiung, Taiwan. (S-KC, C-HL, Y-CC, K-LW, K-CC, T-HH, W- CT); Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital (C-HL).
Medicine (Baltimore). 2016 May;95(19):e3586. doi: 10.1097/MD.0000000000003586.
Summary of Trial Design.Lengthy exposure to quinolone-containing triple therapy in Helicobacter pylori eradication leads to the development of drug resistance. Sequential therapy with a quinolone and metronidazole -containing regimen appears to be an effective treatment option. This randomized controlled trial aimed to compare the efficacy of 5-plus 5 days' levofloxacin and metronidazole-containing sequential therapy (EALM) with that of 10-day levofloxacin-containing triple therapy (EAL) in second-line H pylori eradication treatment.One hundred and sixty-four patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an EALM therapy group (n = 82; esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days) or a 10-day EAL therapy group (n = 82; levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid). One patient was lost to follow-up in each group. Follow-up for H pylori status was performed 4 to 8 weeks later.Eradication rates for the EALM and EAL groups were 90.2% (74/82, 95% confidence interval [CI] = 83.7%-96.8%) and 80.5% (66/82, 95% CI = 71.7%-89.2%, P = 0.077) in the intention-to-treat analysis; and 91.4% (74/81, 95% CI = 85.1%-97.6%) and 81.5% (66/81, 95% CI = 72.8%-90.1%, P = 0.067) in the per-protocol analysis. The adverse events for the EALM and EAL groups were 23.5% versus 11.1%, P = 0.038 but were all very mild and were well tolerated except for 1 patient with poor compliance. The compliances were 98.8% and 100%, respectively, between the 2 groups. An antibiotic resistance to levofloxacin was the clinical factor influencing the efficacy of H. pylori eradication therapy in the EAL group, and dual resistance to levofloxacin and metronidazole in the EALM group.Levofloxacin and metronidazole-containing sequential therapy achieved a >90% eradication rate as a second-line H pylori therapy. Dual antibiotic resistance to levofloxacin and metronidazole was the clinical factor influencing the efficacy of H pylori eradication therapy in the sequential therapy (ClinicalTrials.gov number: NCT02596620).
试验设计总结。在幽门螺杆菌根除治疗中,长时间使用含喹诺酮的三联疗法会导致耐药性的产生。含喹诺酮和甲硝唑的序贯疗法似乎是一种有效的治疗选择。这项随机对照试验旨在比较含左氧氟沙星和甲硝唑的5加5天序贯疗法(EALM)与含左氧氟沙星的10天三联疗法(EAL)在二线幽门螺杆菌根除治疗中的疗效。164例使用标准三联疗法(质子泵抑制剂每日2次,克拉霉素500mg每日2次,阿莫西林1g每日2次×7天)进行幽门螺杆菌根除治疗失败的患者被随机分为EALM治疗组(n = 82;埃索美拉唑40mg每日2次和阿莫西林1g每日2次,持续5天,随后埃索美拉唑40mg每日2次,左氧氟沙星500mg每日1次,甲硝唑500mg每日3次,持续5天)或10天EAL治疗组(n = 82;左氧氟沙星500mg每日1次,阿莫西林1g每日2次,埃索美拉唑40mg每日2次)。每组各有1例患者失访。4至8周后对幽门螺杆菌感染状况进行随访。在意向性分析中,EALM组和EAL组的根除率分别为90.2%(74/82,95%置信区间[CI]=83.7%-96.8%)和80.5%(66/82,95%CI=71.7%-89.2%,P = 0.077);在符合方案分析中,分别为91.4%(74/81,95%CI=85.1%-97.6%)和81.5%(66/81,95%CI=72.8%-90.1%,P = 0.067)。EALM组和EAL组的不良事件发生率分别为23.5%和11.1%,P = 0.038,但均非常轻微,除1例依从性差的患者外,耐受性良好。两组的依从性分别为98.8%和100%。对左氧氟沙星的抗生素耐药性是影响EAL组幽门螺杆菌根除治疗疗效的临床因素,而对左氧氟沙星和甲硝唑的双重耐药性是EALM组的影响因素。含左氧氟沙星和甲硝唑的序贯疗法作为二线幽门螺杆菌治疗的根除率>90%。对左氧氟沙星和甲硝唑的双重抗生素耐药性是影响序贯疗法中幽门螺杆菌根除治疗疗效的临床因素(ClinicalTrials.gov编号:NCT02596620)。