幽门螺杆菌序贯根除治疗
随着幽门螺杆菌耐药性的出现,研究者一直在寻找替代治疗方案,包括使用幽门螺杆菌序贯根除治疗方法。[57]Gatta L, Vakil N, Vaira D, et al. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ. 2013;347:f4587.http://www.bmj.com/content/347/bmj.f4587.longhttp://www.ncbi.nlm.nih.gov/pubmed/23926315?tool=bestpractice.com[58]Liu KS, Hung IF, Seto WK, et al. Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial. Gut. 2014;63:1410-1415.http://gut.bmj.com/content/63/9/1410.longhttp://www.ncbi.nlm.nih.gov/pubmed/24295850?tool=bestpractice.com[59]Molina-Infante J, Romano M, Fernandez-Bermejo M, et al. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology. 2013;145:121-128.http://www.ncbi.nlm.nih.gov/pubmed/23562754?tool=bestpractice.com[60]Francavilla R, Lionetti E, Castellaneta SP, et al. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology. 2005;129:1414-1419.http://www.ncbi.nlm.nih.gov/pubmed/16285942?tool=bestpractice.com[61]Zullo A, Gatta L, de Francesco V, et al. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther. 2005;21:1419-1424.http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02519.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15948808?tool=bestpractice.com 序贯根除治疗的定义是使用一种质子泵抑制剂 (PPI) 加一种抗生素治疗 5 天,随后的 5 天使用 2 或 3 种不同的药物治疗。在意大利的一项研究中,前 5 天使用一种 PPI 和阿莫西林,随后的 5 天使用一种 PPI 和克拉霉素、替硝唑的序贯疗法可使根除率达到 90%以上。[60]Francavilla R, Lionetti E, Castellaneta SP, et al. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology. 2005;129:1414-1419.http://www.ncbi.nlm.nih.gov/pubmed/16285942?tool=bestpractice.com[61]Zullo A, Gatta L, de Francesco V, et al. High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther. 2005;21:1419-1424.http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2005.02519.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15948808?tool=bestpractice.com 此疗法对克拉霉素耐药的患者有效。[62]De Francesco V, Margiotta M, Zullo A, et al. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med. 2006;144:94-100.http://www.ncbi.nlm.nih.gov/pubmed/16418408?tool=bestpractice.com 一项随机、多中心试验比较了 10 日的标准三联疗法与序贯疗法。[63]Zhou L, Zhang J, Chen M, et al. A comparative study of sequential therapy and standard triple therapy for Helicobacter pylori infection: a randomized multicenter trial. Am J Gastroenterol. 2014;109:535-541.http://www.ncbi.nlm.nih.gov/pubmed/24642580?tool=bestpractice.com 进行胃黏膜活检,监测阿莫西林、克拉霉素和甲硝唑药敏。[63]Zhou L, Zhang J, Chen M, et al. A comparative study of sequential therapy and standard triple therapy for Helicobacter pylori infection: a randomized multicenter trial. Am J Gastroenterol. 2014;109:535-541.http://www.ncbi.nlm.nih.gov/pubmed/24642580?tool=bestpractice.com 作者发现两组间清除率没有统计学差异。[63]Zhou L, Zhang J, Chen M, et al. A comparative study of sequential therapy and standard triple therapy for Helicobacter pylori infection: a randomized multicenter trial. Am J Gastroenterol. 2014;109:535-541.http://www.ncbi.nlm.nih.gov/pubmed/24642580?tool=bestpractice.com 在序贯治疗组中,克拉霉素和甲硝唑耐药都是治疗失败的独立预测因子。[63]Zhou L, Zhang J, Chen M, et al. A comparative study of sequential therapy and standard triple therapy for Helicobacter pylori infection: a randomized multicenter trial. Am J Gastroenterol. 2014;109:535-541.http://www.ncbi.nlm.nih.gov/pubmed/24642580?tool=bestpractice.com 另一项研究比较了序贯治疗(例如,一种PPI联合阿莫西林5天,随后的5天给予克拉霉素和甲硝唑)和四联疗法(同样的4种药物使用10天),发现根除率分别为87%和81%。[64]McNicholl AG, Marin AC, Molina-Infante J, et al. Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice. Gut. 2014;63:244-249.http://www.ncbi.nlm.nih.gov/pubmed/23665990?tool=bestpractice.com 作者指出没有研究该人群的抗生素耐药问题。[64]McNicholl AG, Marin AC, Molina-Infante J, et al. Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice. Gut. 2014;63:244-249.http://www.ncbi.nlm.nih.gov/pubmed/23665990?tool=bestpractice.com 一项 meta 分析发现,地域可能会对根除治疗的有效性产生影响。[65]Losurdo G, Leandro G, Principi M, et al. Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'. Int J Clin Pract. 2015;69:1112-1120.http://www.ncbi.nlm.nih.gov/pubmed/26138290?tool=bestpractice.com 将序贯疗法与 14 日疗程的三联疗法进行了比较,并且是按照对甲硝唑/克拉霉素的耐药性低和高的地区对这两种疗法进行了评估。 在对克拉霉素存在高耐药性的地区,序贯疗法要优于 14 日疗程的三联疗法。 在对甲硝唑存在高耐药性的地区,序贯疗法和 14 日疗程的三联疗法的效果相当。[65]Losurdo G, Leandro G, Principi M, et al. Sequential vs. prolonged 14-day triple therapy for Helicobacter pylori eradication: the meta-analysis may be influenced by 'geographical weighting'. Int J Clin Pract. 2015;69:1112-1120.http://www.ncbi.nlm.nih.gov/pubmed/26138290?tool=bestpractice.com 一项针对 6 项随机试验的 meta 分析表明,基于氟喹诺酮的序贯疗法(5-7 日的 PPI 和阿莫西林疗法,接着服用 5-7 日的 PPI、氟喹诺酮和甲硝唑或替硝唑或呋喃唑酮)的根除率与标准序贯疗法(5 日的 PPI 加阿莫西林,接着服用 5 日的 PPI、克拉霉素和甲硝唑或替硝唑)的根除率近似。[66]Kale-Pradhan PB, Mihaescu A, Wilhelm SM. Fluoroquinolone sequential therapy for helicobacter pylori: a meta-analysis. Pharmacotherapy. 2015;35:719-730.http://www.ncbi.nlm.nih.gov/pubmed/26173786?tool=bestpractice.com 作者总结道,基于氟喹诺酮的序贯治疗是一线根除治疗的合理治疗替代方案。[66]Kale-Pradhan PB, Mihaescu A, Wilhelm SM. Fluoroquinolone sequential therapy for helicobacter pylori: a meta-analysis. Pharmacotherapy. 2015;35:719-730.http://www.ncbi.nlm.nih.gov/pubmed/26173786?tool=bestpractice.com 一项 meta 分析显示序贯疗法的疗效下降,并表明序贯疗法目前不是标准治疗的有效替代方案。[67]Nyssen OP, McNicholl AG, Megraud F, et al. Sequential versus standard triple first-line therapy for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2016;(6):CD009034.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009034.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27351542?tool=bestpractice.com
以左氧氟沙星为基础的三联疗法
主要将其作为二线或三线疗法来研究,用于持续性幽门螺杆菌感染患者。一项包括 4 项随机对照试验的 Meta 分析发现,与以铋剂为基础的 7 天四联疗法相比,包含左氧氟沙星的 10 天三联疗法具有更高的根除率和更少的不良反应。[68]Saad RJ, Schoenfeld P, Kim HM, et al. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol. 2006;101:488-496.http://www.ncbi.nlm.nih.gov/pubmed/16542284?tool=bestpractice.com
以利福布汀为基础的治疗
另一种挽救治疗包括 PPI 联合阿莫西林和利福布汀,持续治疗 10 天。研究表明,作为一种挽救治疗方案,在持续性幽门螺杆菌感染患者中,根除率为 38%-91%。[69]Di Mario F, Cavallaro LG, Scarpignato C. 'Rescue' therapies for the management of Helicobacter pylori infection. Dig Dis. 2006;24:113-130.http://www.ncbi.nlm.nih.gov/pubmed/16699270?tool=bestpractice.com
大剂量二联疗法
使用阿莫西林和奥美拉唑的大剂量二联疗法是持续性幽门螺杆菌感染患者的另一种挽救治疗选择。[70]Miehlke S, Kirsch C, Schneider-Brachert W, et al. A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter. 2003;8:310-319.http://www.ncbi.nlm.nih.gov/pubmed/12950604?tool=bestpractice.com
以左氧氟沙星为基础的四联方案
这包括使用左氧氟沙星、奥美拉唑、硝唑尼特和多西环素 (LOAD) 等药物进行治疗。在未经治疗的患者中进行的一项开放性随机临床试验,比较了 7-10 天的 LOAD 方案与标准三联方案:意向治疗分析表明 LOAD 治疗组的幽门螺杆菌根除率明显高于标准三联方案治疗组的。[71]Basu PP, Rayapudi K, Pacana T, et al. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol. 2011;106:1970-1975.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209586/http://www.ncbi.nlm.nih.gov/pubmed/21989146?tool=bestpractice.com应该在根除治疗停止至少 4 周后才能进行粪便抗原检测,以确定根除是否成功。仍需要更大型的随机对照试验来评估这个方案的有效性。
幽门螺杆菌疫苗
一项在中国江苏省进行的双盲、安慰剂对照试验将年龄在 6-15 岁的健康儿童随机分配至接受口服重组幽门螺杆菌疫苗 (n = 2232) 或安慰剂 (n = 2232)。[72]Zeng M, Mao XH, Li JX, et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386:1457-1464.http://www.ncbi.nlm.nih.gov/pubmed/26142048?tool=bestpractice.com 第一年内,出现了 64 例幽门螺杆菌感染事件:疫苗组 14 例,安慰剂组 50 例(疫苗的有效性为 71.8%;95% CI 48.2-85.6)。作者总结道,疫苗可能能够降低幽门螺杆菌感染的发生率,但还需要进行更长期的随访。[72]Zeng M, Mao XH, Li JX, et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386:1457-1464.http://www.ncbi.nlm.nih.gov/pubmed/26142048?tool=bestpractice.com
维生素 C
一项随机对照试验纳入了244名萎缩性胃炎的日本受试者,以评估补充维生素C对活性氧的作用。[73]Sasazuki S, Hayashi T, Nakachi K, et al. Protective effect of vitamin C on oxidative stress: a randomized controlled trial. Int J Vitam Nutr Res. 2008;78:121-128.http://www.ncbi.nlm.nih.gov/pubmed/19003734?tool=bestpractice.com 受试者随机分组,每日服用50mg或500mg维生素C。 和基础值相比,5年后活性氧的变化具有统计学意义。 此外,每天服用500mg的剂量组要比每日50mg的剂量组活性氧下降更加明显。
幽门螺杆菌根除治疗联合益生菌
一项系统评价和网络 Meta 分析发现,益生菌补充的根除方案(7 日补充益生菌的三联疗法和 7 日补充益生菌的基于左氧氟沙星的三联疗法)所致不良事件的发生率低于其他幽门螺杆菌根除方案的。[74]Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ. 2015;351:h4052.http://www.bmj.com/content/351/bmj.h4052.longhttp://www.ncbi.nlm.nih.gov/pubmed/26290044?tool=bestpractice.com
牙周治疗
一项系统评价和 Meta 分析表明,牙周治疗可以提高幽门螺杆菌根除效率,并预防胃部幽门螺杆菌感染复发。[75]Ren Q, Yan X, Zhou Y, et al. Periodontal therapy as adjunctive treatment for gastric Helicobacter pylori infection. Cochrane Database Syst Rev. 2016;(2):CD009477.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009477.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26852297?tool=bestpractice.com [
]In people with gastric Helicobacter pylori infection, what are the effects of periodontal therapy as adjunctive treatment?https://cochranelibrary.com/cca/doi/10.1002/cca.1278/full显示答案
聚普瑞锌
聚普瑞锌是锌和 L-肌肽的一种螯合剂,是一种据说具有促进伤口愈合特性的自由基清除剂。它在日本被批准用于治疗胃溃疡。在一项研究中,与加用安慰剂 (58.9%,p<0.01) 相比,在根除幽门螺杆菌的 14 天的方案中(奥美拉唑、阿莫西林和克拉霉素)加用聚普瑞锌提高了根除率(分别为 77.0% 和 75.9%)。[76]Tan B, Luo HQ, Xu H, et al. Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: A prospective, multicenter, randomized clinical trial. PLoS One. 2017;12(4):e0175625.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28407007/http://www.ncbi.nlm.nih.gov/pubmed/28407007?tool=bestpractice.com