美常安在根除幽门螺杆菌补救治疗方案中的疗效评价
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摘要
目的评价美常安不同给药时机及疗程在H.pylori补救治疗方案中的有效性及安全性。方法将240例H.pylori感染的初治失败患者随机分成4组:D组给予艾司奥美拉唑、阿莫西林、呋喃唑酮、胶体果胶铋治疗2周。A组在D组方案上联用美常安2周。B、C组在D组方案前分别口服美常安4周、2周。治疗结束4周后,行13C-UBT评估H.pylori根除率及不良反应发生率。结果227例完成治疗和随访。意向性治疗(ITT)分析显示,A、B、C、D组根除率分别为73.33%、81.67%、75.00%及61.67%;符合方案集(PP)分析显示,A、B、C、D组根除率分别为77.19%、85.96%、80.36%、64.91%;A、B、C组显著高于D组(P<0.05);B组高于A、C组,差异有统计学意义(P<0.05);A、C组间差异无统计学意义(P>0.05)。A、B、C、D组的不良反应发生率分别为7.02%、5.26%、7.14%、12.28%;A、B、C组显著低于D组(P<0.05),A、B、C组间差异无统计学意义(P>0.05)。结论美常安能有效提高补救治疗方案的H.pylori根除率,减少药物不良反应。补救方案中在四联疗法前服用美常安4周是最优选择,值得临床推广。
Objective To evaluate the efficacy and safety of different treatments of Medilac-S in rescue eradication therapy for Helicobacter pylori( H. pylori) infection. Methods Two hundred and forty H. pylori infected patients after failed initial treatment were randomly divided into 4 groups. Group D underwent a standard quadruple therapy with Esomeprazole,Amoxicillin,Furazolidone and Colloidal bismuth pectin,the course of treatment was 2 weeks. Group A was additionally given Medilac-S for 2 weeks on the basis of group D. Medilac-S was additionally given to group B and group C for 4 weeks and 2 weeks before the same quadruple therapy of group D,respectively. The eradication rate of H. pylori and the incidence of adverse reactions at 4 weeks after treatment were compared among four groups.Results In total,227 patients completed the treatment and follow-up according to the experimental design. Intentionto-treat( ITT) analysis showed that the eradication rates of group A,B,C and D were 73. 33%,81. 67%,75. 00%and 61. 67%; per-protocol( PP) analysis showed that the eradication rates of group A,B,C and D were 77. 19%,85. 96%,80. 36% and 64. 91%,respectively; the eradication rates in group A,B and C were significantly higher than those in group D( P < 0. 05); the eradication rate in group B was significantly higher than those in group A and group C( P < 0. 05); no statistically significant difference was found between group A and group C( P > 0. 05). The incidences of adverse effects in group A,B,C and D were 7. 02%,5. 26%,7. 14% and 12. 28%,respectively. The incidences in group A,B and C were significantly lower than those in group D( P < 0. 05); there was no significant difference in the rate of adverse reactions among group A,B and C( P > 0. 05). Conclusion Medilac-S in rescue therapy can effectively improve the eradication rates of H. pylori infection and decrease the incidence of adverse reactions. It is the best course of 4 weeks of Medilac-S treatment before the quadruple therapy in rescue therapy.
Objective To evaluate the efficacy and safety of different treatments of Medilac-S in rescue eradication therapy for Helicobacter pylori( H. pylori) infection. Methods Two hundred and forty H. pylori infected patients after failed initial treatment were randomly divided into 4 groups. Group D underwent a standard quadruple therapy with Esomeprazole,Amoxicillin,Furazolidone and Colloidal bismuth pectin,the course of treatment was 2 weeks. Group A was additionally given Medilac-S for 2 weeks on the basis of group D. Medilac-S was additionally given to group B and group C for 4 weeks and 2 weeks before the same quadruple therapy of group D,respectively. The eradication rate of H. pylori and the incidence of adverse reactions at 4 weeks after treatment were compared among four groups.Results In total,227 patients completed the treatment and follow-up according to the experimental design. Intentionto-treat( ITT) analysis showed that the eradication rates of group A,B,C and D were 73. 33%,81. 67%,75. 00%and 61. 67%; per-protocol( PP) analysis showed that the eradication rates of group A,B,C and D were 77. 19%,85. 96%,80. 36% and 64. 91%,respectively; the eradication rates in group A,B and C were significantly higher than those in group D( P < 0. 05); the eradication rate in group B was significantly higher than those in group A and group C( P < 0. 05); no statistically significant difference was found between group A and group C( P > 0. 05). The incidences of adverse effects in group A,B,C and D were 7. 02%,5. 26%,7. 14% and 12. 28%,respectively. The incidences in group A,B and C were significantly lower than those in group D( P < 0. 05); there was no significant difference in the rate of adverse reactions among group A,B and C( P > 0. 05). Conclusion Medilac-S in rescue therapy can effectively improve the eradication rates of H. pylori infection and decrease the incidence of adverse reactions. It is the best course of 4 weeks of Medilac-S treatment before the quadruple therapy in rescue therapy.
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.DOI:10.3760/cma.j.issn.0254-1432.2012.10.002.
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[7]谢勇.重视根除幽门螺杆菌预防胃癌[J].中华消化杂志,2017,37(3):158-160.DOI:10.3760/cma.j.issn.0254-1432.2017.03.006.
[8]CUADRADO-LAVIN A,SALCINES-CAVIEDES J R,CARRASCOSA M F,et al.Levofloxacin versus clarithromycin in a 10 day triple therapy regimen for first-line Helicobacter pylori eradication:a single-blind randomized clinical trial[J].J Antimicrob Chemother,2012,67(9):2254-2259.DOI:10.1093/jac/dks209.
[9]张建中.中国幽门螺杆菌治疗低根除率现状及应对策略[J].胃肠病学和肝病学杂志,2017,26(6):637-639.DOI:10.3969/j.issn.1006-5709.2017.06.005.ZHANG J Z.Current status and countermeasures of low eradication rate of Helicobacter pylori in China[J].Chin J Gastroenterol Hepatol,2017,26(6):637-639.DOI:10.3969/j.issn.1006-5709.2017.06.005.
[10]GEORGOPOULOS S D,PAPASTERGIOU V,KARATAPANI S.Current options for the treatment of Helicobacter pylori[J].Expert Opin Pharmacother,2013,14(2):211-223.DOI:10.1517/14656566.2013.763926.
[11]LV Z,WANG B,ZHOU X,et al.Efficacy and safety of probiotics as adjuvant agents for infection:A meta-analysis[J].Exp Ther Med,2015,9(3):707-716.DOI:10.3892/etm.2015.2174.
[12]DANG Y,REINHARDT J D,ZHOU X,et al.The effect of probiotics supplementation on Helicobacter pylori eradication rates and side effects during eradication therapy:a meta-analysis[J].PLo S One,2014,9(11):e111030.DOI:10.1371/journal.pone.0111030.
[13]ABDALLAH J,HASSAN T,KYPRIANOU A.Re:proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients[J].Am J Gastroenterol,2014,109(4):601-602.DOI:10.1038/ajg.2013.481.
[14]ZHERNAKOVA A,KURILSHIKOV A,BONDER M J,et al.Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity[J].Science,2016,352(6285):565-569.DOI:10.1126/science.aad3369.
[15]JACKSON M A,GOODRICH J K,MAXAN M E,et al.Proton pump inhibitors alter the composition of the gut microbiota[J].Gut,2016,65(5):749-756.DOI:10.1136/gutjnl-2015-310861.
[16]FREEDBERG D E,TOUSSAINT N C,CHEN S P,et al.Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome:a crossover trial[J].Gastroenterology,2015,149(4):883-885.DOI:10.1053/j.gastro.2015.06.043.
[17]KARCZEWSKI J,TROOST F J,KONINGS I,et al.Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier[J].Am J Physiol Gastrointest Liver Physiol,2010,298(6):G851-G859.DOI:10.1152/ajpgi.00327.2009.
[18]YANG Y J,SHEU B S.Probiotics-containing yogurts suppress Helicobacter pylori load and modify immune response and intestinal microbiota in the Helicobacter pylori-infected children[J].Helicobacter,2012,17(4):297-304.DOI:10.1111/j.1523-5378.2012.00941.x.
[19]DEGUCHI R,NAKAMINAMI H,RIMBARA E,et al.Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy[J].J Gastroenterol Hepatol,2012,27(5):888-892.DOI:10.1111/j.1440-1746.2011.06985.x.
[20]OH B,KIM B S,KIM J W,et al.The effect of probiotics on gut microbiota during the Helicobacter pylori eradication:randomized controlled trial[J].Helicobacter,2016,21(3):165-174.DOI:10.1111/hel.12270.
[21]ZHANG M M,QIAN W,QIN Y Y,et al.Probiotics in Helicobacter pylori eradication therapy:a systematic review and meta-analysis[J].World J Gastroenterol,2015,21(14):4345-4357.DOI:10.3748/wjg.v21.i14.4345.
[22]HOMAN M,OREL R.Are probiotics useful in Helicobacter pylori eradication?[J].World J Gastroenterol,2015,21(37):10644-10653.DOI:10.3748/wjg.v21.i37.10644.
[23]FALLONE C A,CHIBA N,VANZANTEN S V,et al.The Toronto consensus for the treatment of Helicobacter pylori infection in adults[J].Gastroenterology,2016,151(1):51-69.DOI:10.1053/j.gastro.2016.04.006.
[24]MALFERTHEINER P,MEGRRAUD F,O’MORAIN C A,et al.Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report[J].Gut,2017,66(1):6-30.DOI:10.1136/gutjnl-2016-312288.
[25]SHEU B S,CHENG H C,KAO A W,et al.Pretreatment with Lactobacillus-and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy[J].Am J Clin Nutr,2006,83(4):864-869.
[26]DU Y Q,SU T,FAN J G,et al.Adjuvant probiotics improve the eradication effect of triple therapy for Helicobacter pylori infection[J].World J Gastroenterol,2012,18(43):6302-6307.DOI:10.3748/wjg.v18.i43.6302.
[2]MALFERTHEINER P,MEGRAUD F,O’MORAIN C A,et al.Management of Helicobacter pylori infection-the MaastrichtⅣ/Florence Consensus Report[J].Gut,2012,61(5):646-664.DOI:10.1136/gutjnl-2012-302084.
[3]HUNT R H,XIAO S D,MEGRAUD F,et al.Helicobacter pylori in developing countries.World Gastroenterology Organisation Global Guideline[J].J Gastrointestin Liver Dis,2011,20(3):299-304.
[4]MANDEVILLE K L,KRABSHUIS J,LADEP N G,et al.Gastroenterology in developing countries:issues and advances[J].World J Gastroenterol,2009,15(23):2839-2854.DOI:10.3748/wjg.15.2839.
[5]中国幽门螺杆菌科研协作组.中国自然人群幽门螺杆菌感染的流行病学调查[J].现代消化及介入诊疗,2010,15(5):265-270.The Team of Collaboration of Helicobacter pylori research in China.Prvalence of Helicobacter pylori infection in China[J].Modern Digestion&Intervention,2010,15(5):265-270.
[6]SUGANO K,TACK J,KUIPERS E J,et al.Kyoto global consensus report on Helicobacter pylori gastritis[J].Gut,2015,64(9):1353-1367.DOI:10.1136/gutjnl-2015-309252.
[7]谢勇.重视根除幽门螺杆菌预防胃癌[J].中华消化杂志,2017,37(3):158-160.DOI:10.3760/cma.j.issn.0254-1432.2017.03.006.
[8]CUADRADO-LAVIN A,SALCINES-CAVIEDES J R,CARRASCOSA M F,et al.Levofloxacin versus clarithromycin in a 10 day triple therapy regimen for first-line Helicobacter pylori eradication:a single-blind randomized clinical trial[J].J Antimicrob Chemother,2012,67(9):2254-2259.DOI:10.1093/jac/dks209.
[9]张建中.中国幽门螺杆菌治疗低根除率现状及应对策略[J].胃肠病学和肝病学杂志,2017,26(6):637-639.DOI:10.3969/j.issn.1006-5709.2017.06.005.ZHANG J Z.Current status and countermeasures of low eradication rate of Helicobacter pylori in China[J].Chin J Gastroenterol Hepatol,2017,26(6):637-639.DOI:10.3969/j.issn.1006-5709.2017.06.005.
[10]GEORGOPOULOS S D,PAPASTERGIOU V,KARATAPANI S.Current options for the treatment of Helicobacter pylori[J].Expert Opin Pharmacother,2013,14(2):211-223.DOI:10.1517/14656566.2013.763926.
[11]LV Z,WANG B,ZHOU X,et al.Efficacy and safety of probiotics as adjuvant agents for infection:A meta-analysis[J].Exp Ther Med,2015,9(3):707-716.DOI:10.3892/etm.2015.2174.
[12]DANG Y,REINHARDT J D,ZHOU X,et al.The effect of probiotics supplementation on Helicobacter pylori eradication rates and side effects during eradication therapy:a meta-analysis[J].PLo S One,2014,9(11):e111030.DOI:10.1371/journal.pone.0111030.
[13]ABDALLAH J,HASSAN T,KYPRIANOU A.Re:proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients[J].Am J Gastroenterol,2014,109(4):601-602.DOI:10.1038/ajg.2013.481.
[14]ZHERNAKOVA A,KURILSHIKOV A,BONDER M J,et al.Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity[J].Science,2016,352(6285):565-569.DOI:10.1126/science.aad3369.
[15]JACKSON M A,GOODRICH J K,MAXAN M E,et al.Proton pump inhibitors alter the composition of the gut microbiota[J].Gut,2016,65(5):749-756.DOI:10.1136/gutjnl-2015-310861.
[16]FREEDBERG D E,TOUSSAINT N C,CHEN S P,et al.Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome:a crossover trial[J].Gastroenterology,2015,149(4):883-885.DOI:10.1053/j.gastro.2015.06.043.
[17]KARCZEWSKI J,TROOST F J,KONINGS I,et al.Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier[J].Am J Physiol Gastrointest Liver Physiol,2010,298(6):G851-G859.DOI:10.1152/ajpgi.00327.2009.
[18]YANG Y J,SHEU B S.Probiotics-containing yogurts suppress Helicobacter pylori load and modify immune response and intestinal microbiota in the Helicobacter pylori-infected children[J].Helicobacter,2012,17(4):297-304.DOI:10.1111/j.1523-5378.2012.00941.x.
[19]DEGUCHI R,NAKAMINAMI H,RIMBARA E,et al.Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy[J].J Gastroenterol Hepatol,2012,27(5):888-892.DOI:10.1111/j.1440-1746.2011.06985.x.
[20]OH B,KIM B S,KIM J W,et al.The effect of probiotics on gut microbiota during the Helicobacter pylori eradication:randomized controlled trial[J].Helicobacter,2016,21(3):165-174.DOI:10.1111/hel.12270.
[21]ZHANG M M,QIAN W,QIN Y Y,et al.Probiotics in Helicobacter pylori eradication therapy:a systematic review and meta-analysis[J].World J Gastroenterol,2015,21(14):4345-4357.DOI:10.3748/wjg.v21.i14.4345.
[22]HOMAN M,OREL R.Are probiotics useful in Helicobacter pylori eradication?[J].World J Gastroenterol,2015,21(37):10644-10653.DOI:10.3748/wjg.v21.i37.10644.
[23]FALLONE C A,CHIBA N,VANZANTEN S V,et al.The Toronto consensus for the treatment of Helicobacter pylori infection in adults[J].Gastroenterology,2016,151(1):51-69.DOI:10.1053/j.gastro.2016.04.006.
[24]MALFERTHEINER P,MEGRRAUD F,O’MORAIN C A,et al.Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report[J].Gut,2017,66(1):6-30.DOI:10.1136/gutjnl-2016-312288.
[25]SHEU B S,CHENG H C,KAO A W,et al.Pretreatment with Lactobacillus-and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy[J].Am J Clin Nutr,2006,83(4):864-869.
[26]DU Y Q,SU T,FAN J G,et al.Adjuvant probiotics improve the eradication effect of triple therapy for Helicobacter pylori infection[J].World J Gastroenterol,2012,18(43):6302-6307.DOI:10.3748/wjg.v18.i43.6302.