基于莫西沙星和铋剂的四联疗法对幽门螺杆菌根除失败后的补救治疗
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摘要
【目的】评价基于莫西沙星和铋剂的四联疗法对幽门螺杆菌根除失败后进行补救治疗的有效性和安全性。【方法】应用前瞻性、随机、对照研究的方法,将符合入选标准的患者136例随机分为拓展四联方案组(66例)和经典四联方案组(70例),分别按照拓展四联方案(胶体果胶铋100 mg tid+兰索拉唑30 mg bid+阿莫西林1000 mg bid+莫西沙星400 mg qd联用)和经典铋剂四联方案(胶体果胶铋100 mg tid+兰索拉唑30 mg bid+四环素片750 mg bid+甲硝唑片400 mg bid联用),疗程均为14 d。在治疗结束1月后,分别对两组患者进行内镜检查、快速尿素酶试验和13碳/14碳尿素酶呼气试验进行疗效评价,并对药物不良反应和依从性进行监测。【结果】拓展四联方案组60例完成最后的治疗及随访,其中55例补救治疗获得成功,按照意向治疗(ITT)和符合方案(PP)补救治疗Hp根除率分别为83.3%(55/66)和91.7%(55/60)。经典四联方案组64例完成最后的治疗及随访,其中37例补救治疗获得成功,按照意向治疗(ITT)和符合方案(PP)补救治疗Hp根除率分别为52.9%(37/70)和57.8%(37/64),差异均有统计学意义(P<0.001)。药物不良反应和依从性方面的监测结果显示,两组患者差异无统计学意义(P>0.05)。【结论】基于莫西沙星和铋剂的四联疗法对初次幽门螺杆菌根除失败后进行补救治疗的根除率高于经典的铋剂四联方案,在安全性方面与经典铋剂四联方案无异,具备作为初次Hp根除失败后进行补救治疗方案的基本条件。
【Objective】To evaluate the efficacy and safety of quadruple therapy based on moxifloxacin and bismuth in the treatment of Helicobacter pylori eradication failure.【Methods】A prospective,randomized,comparative study was conducted in which 136 eligible patients were randomly divided into the extended quadruple group(66 patients,and the quadruplex therapies are Pectin bismuth 100 mg tid + lansoprazole 30 mg bid + amoxicillin 1000 mg bid + moxifloxacin 400 mg qd)and the classical quadruple group(70 patients,and the quadruple therapies are colloidal pectin bismuth 100 mg tid + lansoprazole 30 mg bid +tetracycline tablet 750 mg Bid + metronidazole tablets 400 mg bid combination)and were under treatment for 14 days. One month after the treatment,endoscopy,rapid urease test,and 13-carbon/14-carbon urease breath test were used to evaluate the adverse effects and adherence of the drugs in the two groups respectively.【Results】In the extended quadruple group,among 60 patients who had completed the final treatment and follow-up survey,55 were successfully treated,with eradication rates of(83.3%,55/66)and 91.7%(55/60)according to intention-to-treat(ITT)and Per-protocol(PP)respectively. In the classic quadruple group,64 patients completed the final treatment and follow-up survey. Among them,37 cases were successful,and the eradication rates according to ITT and PP remedy are 52.9%(37/70)and 57.8%(37/64)respectively. The difference was statistically significant(P < 0.001). Adverse drug reactions and compliance monitoring showed no significant difference between the two groups(P > 0.05).【Conclusion】The quadruple therapy based on moxifloxacin and bismuth displays a higher eradication rate than that of the classical bismuth quadruple therapy on the first-time elimination failure of Helicobacter pylori while shows no difference in safety consideration,thus can serve as remedial therapy for the primary Hp eradication failure.
【Objective】To evaluate the efficacy and safety of quadruple therapy based on moxifloxacin and bismuth in the treatment of Helicobacter pylori eradication failure.【Methods】A prospective,randomized,comparative study was conducted in which 136 eligible patients were randomly divided into the extended quadruple group(66 patients,and the quadruplex therapies are Pectin bismuth 100 mg tid + lansoprazole 30 mg bid + amoxicillin 1000 mg bid + moxifloxacin 400 mg qd)and the classical quadruple group(70 patients,and the quadruple therapies are colloidal pectin bismuth 100 mg tid + lansoprazole 30 mg bid +tetracycline tablet 750 mg Bid + metronidazole tablets 400 mg bid combination)and were under treatment for 14 days. One month after the treatment,endoscopy,rapid urease test,and 13-carbon/14-carbon urease breath test were used to evaluate the adverse effects and adherence of the drugs in the two groups respectively.【Results】In the extended quadruple group,among 60 patients who had completed the final treatment and follow-up survey,55 were successfully treated,with eradication rates of(83.3%,55/66)and 91.7%(55/60)according to intention-to-treat(ITT)and Per-protocol(PP)respectively. In the classic quadruple group,64 patients completed the final treatment and follow-up survey. Among them,37 cases were successful,and the eradication rates according to ITT and PP remedy are 52.9%(37/70)and 57.8%(37/64)respectively. The difference was statistically significant(P < 0.001). Adverse drug reactions and compliance monitoring showed no significant difference between the two groups(P > 0.05).【Conclusion】The quadruple therapy based on moxifloxacin and bismuth displays a higher eradication rate than that of the classical bismuth quadruple therapy on the first-time elimination failure of Helicobacter pylori while shows no difference in safety consideration,thus can serve as remedial therapy for the primary Hp eradication failure.
引文
[1]中华医学会消化病学分会幽门螺杆菌学组/全国幽门螺杆菌研究协作组.第四次全国幽门螺杆菌感染处理共识报告[J].中华消化杂志,2012,32(10):655-661.Helicobacter Pylori Research Sector,Digestive Disease Branch of Chinese Medical Association/National Heli.cobacter Pylori Research Collaboration Group.Fourth National Helicobacter Pylori Infection Treatment Con.sensus Report[J].Chin J Dig,2012,32(10):655-661.
[2]缑琼英,施瑞华,喻荣斌,等.左氧氟沙星优化三联方案根除幽门螺旋杆菌的Meta分析[J].世界华人消化杂志,2014,22(33):5207-5211.Gou QY,Shi RH,Yu RB,et al.Meta-analysis of erad.ication of Helicobacter pylori by levofloxacin optimiza.tion triple therapy[J].World Chin J Digestol,2014,22(33):5207-5211.
[3]中华医学会消化病学分会幽门螺杆菌学组.幽门螺杆菌胃炎京都全球共识研讨会纪要[J].中华消化杂志,2016,36(1):53-57.Helicobacter Pylori Research Sector,Digestive Disease Branch of Chinese Medical Association.Seminar sum.mary of Kyoto global consensus on Helicobacter pylori gastritis[J].Chin J Dig,2016,36(1):53-57.
[4]刘文忠.“幽门螺杆菌胃炎京都全球共识”解读[J].胃肠病学杂志,2015,20(8):449-456.Liu WZ.Interpretation of Kyoto global consensus on Helicobacter pylori gastritis[J].Chin J Gastroenterol,2015,20(8):449-456.
[5]刘文忠.《幽门螺杆菌感染的处理:MaastrichtV/Flor.ence共识报告》解读[J].胃肠病学杂志,2016,21(10):577-584.Liu WZ.Interpretation of“Management of Helicobacter pylori infection-the MaastrichtⅤ/Florence consensus report”[J].Chin J Gastroenterol,2016,21(10):577-584.
[6]Yan Y,Xiao W,Jing-Yao F,et al.Impact of concomi.tant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome[J].J Geriatr Cardiol(Engl Ver),2016,13(3):209-217.
[7]王翔军,任永强,王新花,等.胃幽门螺杆菌感染情况诊断中快速尿素酶试验检测应用的价值[J].中国卫生检验杂志,2014,24(23):3436-3437.Wang XJ,Ren YQ,Wang XH,et al.The Application Value of Rapid Urease Test Applied in Diagnosis of He.licobacter pylori Infection[J].Chin J Health Lab Tech.nol,2014,24(23):3436-3437.
[8]冯跃,张澍田.质子泵抑制剂使用的远期不良反应[J].中华消化杂志,2015,35(8):567-570.Feng Y,Zhang ST.Long-term adverse reactions of pro.ton pump inhibitors[J].Chin J Digest,2015,35(8):567-570.
[9]司小北,蓝宇.长期使用质子泵抑制剂的不良反应[J].药物不良反应杂志,2015(3):218-221.Si XB,Lan Y.Adverse reactions of chronic use of pro.ton pump inhibitors[J].Adv Drug React J,2015(3):218-221.567
[10]刘芳勋,张晶,张华,等.铋剂在幽门螺杆菌根除中的不良反应及预防[J].临床药物治疗杂志,2014,12(5):59-62.Liu FX,Zhang J,Zhang H,et al.Types and Preven.tion of adverse reactions related with bismuth-contain.ing regimens for Helicobacter pylori eradication[J].Clin Medic J,2014,12(5):59-62.
[11]贾占民,齐立民,李博,等.含四环素三联方案根除幽门螺杆菌感染疗效观察[J].胃肠病学杂志,2013,18(12):744-746.Jia ZM,Qi LM,Li B,et al.Efficacy of tetracyclinecontaining triple therapy for eradication of Helicobacter pylori infection[J].Chin J Gastroenterol,2013,18(12):744-746.
[12]赵惠君.阿莫西林不良反应分析[J].临床医学杂志,2016,36(8):114.Zhao HJ.Adverse Reaction Analysis of Amoxicillin[J].Clinical Medicine,2016,36(8):114.
[13]Sugano K,Tack J,Kuipers EJ,et al.Faculty members of kyoto global consensus conference.kyoto global con.sensus report on helicobacter pylori gastritis[J].Gut,2015,64(9):1353-1367.
[14]牛占岳,宋志强,周丽雅,等.中国大陆地区成人幽门螺杆菌耐药情况及变迁[J].中华内科杂志,2016,55(9):734-736.Niu ZY,Song ZQ,Zhou LY,et al.Resistance of Heli.cobacter pylori of adults in mainland China[J].Chin JIntern Med,2016,55(9):734-736.
[15]Zhou L,Zhang J,Song Z,et al.Tailored versus triple plus bismuth or concomitant therapy as initial helico.bacter pylori treatment:a randomized trial[J].Helico.bacter,2016,21(2):91-99.
[16]曾丽妮,练海燕,王文卿,等.改良序贯疗法补救治疗幽门螺旋杆菌感染的临床疗效[J].世界华人消化杂志,2015,23(36):5894-5897.Zeng LN,Lian HY,Wang WQ,et al.Clinical efficacy of modified sequential therapy in rescue therapy of Heli.cobacter pylori infection[J].World Chin J Digestol,2015,23(36):5894-5897.
[17]王慧.基于莫西沙星和埃索美拉唑镁的三联疗法对幽门螺旋杆菌根除效果的临床观察[J].山东大学学报(医学版),2014,52(8):52-56.Wang H.Clinical observation of triple therapy of moxi.floxacin and esomeprazole magnesium for Helicobacter pylori[J].J Shandong Univ(Health Sci),2014,52(8):52-56.
[18]黄景荣,屈银宗,赵莉,等.含莫西沙星三联疗法和含左氧氟沙星三联疗法作为幽门螺杆菌感染二线治疗568的比较[J].临床消化病杂志,2013,25(6):368-370.Huang JR,Qu YZ,Zhao L,et al.Comparison of moxi.floxacin-based triple therapy and levofloxacin-based tri.ple therapy as second-line treatment for Helicobacter pylori infection[J].Chin J Clin Gastroenterol,2013,25(6):368-370.
[19]王小平.含左氧氟沙星序贯疗法补救治疗幽门螺旋杆菌感染的疗效[J].中国医药指南杂志,2016,14(28):106-106.Wang XP.Remedial effect of sequential therapy with le.vofloxacin in the treatment of Helicobacter pylori[J].Guide Chin Med,2016,14(28):106-106.
[20]王海龙,赵晓红,侯瑞瑞,等.莫西沙星三联方案对根除耐药幽门螺杆菌的临床研究[J].宁夏医学杂志,2013,35(12):1203-1204.Wang HR,Zhao XH,Hou RR,et al.Clinical study on the drug-resistance eradication of Helicobacter pylori by moxifloxacin triple therapy[J].Ningxia Med J,2013,35(12):1203-1204.
[21]Zhang YX,Zhou LY,Song ZQ,et al.Primary antibiot.ic resistance of helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing:a prospec.tive serial study[J].World J Gastroenterol,2015,21(9):2786-2792.
[22]张维,陆红.含铋剂的根除幽门螺杆菌方案在我国应用的经验与建议[J].中华消化杂志,2014,34(9):646-648.Zhang W,Lu H.Experience and recommendations of bismuth-containing treatment in the eradication of Heli.cobacter pylori in China[J].Chin J Digest,2014,34(9):646-648.
[23]Graham DY,Dore MP.Helicobacter pylori therapy:a paradigm shift[J].Expert Rev Anti Infect Ther,2016,14(6):577-585.
[24]张健,李洪运.四联疗法根治幽门螺旋杆菌感染疗效分析[J].中国病原生物学杂志,2014,9(8):747-749.Zhang J,Li HY.Analysis of the therapeutic effective.ness of a quadruple drug therapy to eradicate Helico.bacter pylori[J].J Pathogen Biol,2014,9(8):747-749.
[25]郑小丽,许乐.含呋喃唑酮四联疗法对幽门螺杆菌多次根除失败患者的疗效[J].中华医学杂志,2013,93(44):3496-3499.Zheng XL,Xu L.Remedial effect of furazolidone-con.taining quadruple therapy on Helicobacter pylori eradi.cation failure[J].Natl Med J China,2013,93(44):3496-3499.
[2]缑琼英,施瑞华,喻荣斌,等.左氧氟沙星优化三联方案根除幽门螺旋杆菌的Meta分析[J].世界华人消化杂志,2014,22(33):5207-5211.Gou QY,Shi RH,Yu RB,et al.Meta-analysis of erad.ication of Helicobacter pylori by levofloxacin optimiza.tion triple therapy[J].World Chin J Digestol,2014,22(33):5207-5211.
[3]中华医学会消化病学分会幽门螺杆菌学组.幽门螺杆菌胃炎京都全球共识研讨会纪要[J].中华消化杂志,2016,36(1):53-57.Helicobacter Pylori Research Sector,Digestive Disease Branch of Chinese Medical Association.Seminar sum.mary of Kyoto global consensus on Helicobacter pylori gastritis[J].Chin J Dig,2016,36(1):53-57.
[4]刘文忠.“幽门螺杆菌胃炎京都全球共识”解读[J].胃肠病学杂志,2015,20(8):449-456.Liu WZ.Interpretation of Kyoto global consensus on Helicobacter pylori gastritis[J].Chin J Gastroenterol,2015,20(8):449-456.
[5]刘文忠.《幽门螺杆菌感染的处理:MaastrichtV/Flor.ence共识报告》解读[J].胃肠病学杂志,2016,21(10):577-584.Liu WZ.Interpretation of“Management of Helicobacter pylori infection-the MaastrichtⅤ/Florence consensus report”[J].Chin J Gastroenterol,2016,21(10):577-584.
[6]Yan Y,Xiao W,Jing-Yao F,et al.Impact of concomi.tant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome[J].J Geriatr Cardiol(Engl Ver),2016,13(3):209-217.
[7]王翔军,任永强,王新花,等.胃幽门螺杆菌感染情况诊断中快速尿素酶试验检测应用的价值[J].中国卫生检验杂志,2014,24(23):3436-3437.Wang XJ,Ren YQ,Wang XH,et al.The Application Value of Rapid Urease Test Applied in Diagnosis of He.licobacter pylori Infection[J].Chin J Health Lab Tech.nol,2014,24(23):3436-3437.
[8]冯跃,张澍田.质子泵抑制剂使用的远期不良反应[J].中华消化杂志,2015,35(8):567-570.Feng Y,Zhang ST.Long-term adverse reactions of pro.ton pump inhibitors[J].Chin J Digest,2015,35(8):567-570.
[9]司小北,蓝宇.长期使用质子泵抑制剂的不良反应[J].药物不良反应杂志,2015(3):218-221.Si XB,Lan Y.Adverse reactions of chronic use of pro.ton pump inhibitors[J].Adv Drug React J,2015(3):218-221.567
[10]刘芳勋,张晶,张华,等.铋剂在幽门螺杆菌根除中的不良反应及预防[J].临床药物治疗杂志,2014,12(5):59-62.Liu FX,Zhang J,Zhang H,et al.Types and Preven.tion of adverse reactions related with bismuth-contain.ing regimens for Helicobacter pylori eradication[J].Clin Medic J,2014,12(5):59-62.
[11]贾占民,齐立民,李博,等.含四环素三联方案根除幽门螺杆菌感染疗效观察[J].胃肠病学杂志,2013,18(12):744-746.Jia ZM,Qi LM,Li B,et al.Efficacy of tetracyclinecontaining triple therapy for eradication of Helicobacter pylori infection[J].Chin J Gastroenterol,2013,18(12):744-746.
[12]赵惠君.阿莫西林不良反应分析[J].临床医学杂志,2016,36(8):114.Zhao HJ.Adverse Reaction Analysis of Amoxicillin[J].Clinical Medicine,2016,36(8):114.
[13]Sugano K,Tack J,Kuipers EJ,et al.Faculty members of kyoto global consensus conference.kyoto global con.sensus report on helicobacter pylori gastritis[J].Gut,2015,64(9):1353-1367.
[14]牛占岳,宋志强,周丽雅,等.中国大陆地区成人幽门螺杆菌耐药情况及变迁[J].中华内科杂志,2016,55(9):734-736.Niu ZY,Song ZQ,Zhou LY,et al.Resistance of Heli.cobacter pylori of adults in mainland China[J].Chin JIntern Med,2016,55(9):734-736.
[15]Zhou L,Zhang J,Song Z,et al.Tailored versus triple plus bismuth or concomitant therapy as initial helico.bacter pylori treatment:a randomized trial[J].Helico.bacter,2016,21(2):91-99.
[16]曾丽妮,练海燕,王文卿,等.改良序贯疗法补救治疗幽门螺旋杆菌感染的临床疗效[J].世界华人消化杂志,2015,23(36):5894-5897.Zeng LN,Lian HY,Wang WQ,et al.Clinical efficacy of modified sequential therapy in rescue therapy of Heli.cobacter pylori infection[J].World Chin J Digestol,2015,23(36):5894-5897.
[17]王慧.基于莫西沙星和埃索美拉唑镁的三联疗法对幽门螺旋杆菌根除效果的临床观察[J].山东大学学报(医学版),2014,52(8):52-56.Wang H.Clinical observation of triple therapy of moxi.floxacin and esomeprazole magnesium for Helicobacter pylori[J].J Shandong Univ(Health Sci),2014,52(8):52-56.
[18]黄景荣,屈银宗,赵莉,等.含莫西沙星三联疗法和含左氧氟沙星三联疗法作为幽门螺杆菌感染二线治疗568的比较[J].临床消化病杂志,2013,25(6):368-370.Huang JR,Qu YZ,Zhao L,et al.Comparison of moxi.floxacin-based triple therapy and levofloxacin-based tri.ple therapy as second-line treatment for Helicobacter pylori infection[J].Chin J Clin Gastroenterol,2013,25(6):368-370.
[19]王小平.含左氧氟沙星序贯疗法补救治疗幽门螺旋杆菌感染的疗效[J].中国医药指南杂志,2016,14(28):106-106.Wang XP.Remedial effect of sequential therapy with le.vofloxacin in the treatment of Helicobacter pylori[J].Guide Chin Med,2016,14(28):106-106.
[20]王海龙,赵晓红,侯瑞瑞,等.莫西沙星三联方案对根除耐药幽门螺杆菌的临床研究[J].宁夏医学杂志,2013,35(12):1203-1204.Wang HR,Zhao XH,Hou RR,et al.Clinical study on the drug-resistance eradication of Helicobacter pylori by moxifloxacin triple therapy[J].Ningxia Med J,2013,35(12):1203-1204.
[21]Zhang YX,Zhou LY,Song ZQ,et al.Primary antibiot.ic resistance of helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing:a prospec.tive serial study[J].World J Gastroenterol,2015,21(9):2786-2792.
[22]张维,陆红.含铋剂的根除幽门螺杆菌方案在我国应用的经验与建议[J].中华消化杂志,2014,34(9):646-648.Zhang W,Lu H.Experience and recommendations of bismuth-containing treatment in the eradication of Heli.cobacter pylori in China[J].Chin J Digest,2014,34(9):646-648.
[23]Graham DY,Dore MP.Helicobacter pylori therapy:a paradigm shift[J].Expert Rev Anti Infect Ther,2016,14(6):577-585.
[24]张健,李洪运.四联疗法根治幽门螺旋杆菌感染疗效分析[J].中国病原生物学杂志,2014,9(8):747-749.Zhang J,Li HY.Analysis of the therapeutic effective.ness of a quadruple drug therapy to eradicate Helico.bacter pylori[J].J Pathogen Biol,2014,9(8):747-749.
[25]郑小丽,许乐.含呋喃唑酮四联疗法对幽门螺杆菌多次根除失败患者的疗效[J].中华医学杂志,2013,93(44):3496-3499.Zheng XL,Xu L.Remedial effect of furazolidone-con.taining quadruple therapy on Helicobacter pylori eradi.cation failure[J].Natl Med J China,2013,93(44):3496-3499.