幽门螺杆菌根除治疗失败后的补救治疗

幽门螺杆菌（H.pylori)对抗生素的耐药率上升是导致根除治疗失败率上升的主要原因，对经标准方案根除H.pylori失败的患者有必要进行补救治疗。目的：评估铋剂、质子泵抑制剂（PPI）联用呋喃唑酮和四环素组成的7天四联方案用于根除H.pylori治疗失败后补救治疗的疗效，以及H.pylori耐药对疗效的影响。方法：予35例经含克拉霉素根除H.pylori方案治疗、H.pylori仍为阳性的患者以为期7天的四联治疗：枸橼酸铋钾220mg bid 奥美拉唑20mg bid 呋喃唑酮100mg bid 四环素750mg bid。治疗前取胃窦黏膜活检标本进行快速尿素酶试验、组织学检查和培养检测H.pylori。用琼脂扩散法测定克拉霉素、呋喃唑酮和四环素的最低抑菌浓度（MIC）。治疗结束后至少4周，采用^13C-尿素呼气试验进行H.pylori感染状态评估。结果：33例患者完成治疗和随访，2例失访。根据意图治疗（ITT）和试验方案（PP）分析，该补救方案的H.pylori根除率分别为68．6％（24／35）和72．7％（24／33）。10例（28．6％）患者发生轻度副反应（9例发生恶心、中上腹不适，1例发生皮疹）。35例中有27例H.pylori培养成功，克拉霉素的耐药率为51．8％（14／27），呋喃唑酮为3．7％（1／27），四环素为7．4％（2／27）。各药物耐药菌株和敏感菌株的H.pylori根除率无显著差异。结论：铋剂、PPI联用呋喃唑酮和四环素组成的7天联方案作为根除H.pylori治疗失败后的补救治疗可获得较高的H.pylori根除率。     

评估以雷贝拉唑为基础的三联和四联方案根除幽门螺杆菌的疗效

背景：在标准三联方案对幽门螺杆菌（H.pylori）感染根除率有所下降的情况下，首选含铋剂的四联方案是否较标准三联方案更具优势？目的：比较以雷贝拉唑为基础的标准三联方案和再加铋剂的四联方案对H.pylori感染者进行初次根除治疗的疗效。方法：65例内镜诊断为非溃疡性消化不良的H.pylori感染者随机分配至三联组（雷贝拉唑10mg bid＋克拉霉素500mg bid＋阿莫西林1．0g bid）和四联组（上述三联药物加胶体次枸橼酸铋220mg bid），连服7天。治疗结束后至少间隔4周复查^13C-尿素呼气试验检测H.pylori，评估治疗结果。结果：60例患者按方案完成治疗。三联组和四联组H．prlori根除率按意图治疗（ITT）分析分别为71．9％和75．8％，按方案（PP）分析分别为76．7％和83．3％，两组间根除率无显著差异（P〉0．05）。除四联组中有2例分别因头晕和上腹痛而未完成治疗外，两组其余患者的不良反应相似，且能耐受，停药后不良反应自行消失。结论：含雷贝拉唑、克拉霉素和阿莫西林的一周三联治疗方案与再加铋剂的四联方案均能有效根除H.pylori，加用铋剂并未显著提高H.pylori的根除率，提示首次根除H.pylori治疗时仍应选择含质子泵抑制剂和两种抗生素的三联方案。     

含左氧氟沙星的四联方案补救治疗幽门螺杆菌的临床研究

目的 评价含左氧氟沙星的四联方案补救治疗幽门螺杆菌的有效性和安全性。方法 33例幽门螺杆菌初次根除失败的消化性溃疡或慢性萎缩性胃炎患者接受了下述10天含左氧氟沙星的四联方案：质子泵抑制剂（标准剂量）＋枸橼酸铋钾（0．22g）＋左旋氧氟沙星（0．2g）＋阿莫西林（1．0g）b．d，4周后通过^13C-尿素酶呼吸试验判断根除成功与否。结果 2例失访，余31例完成治疗及随访，其中26例补救根除成功，5例补救治疗失败，6例（18．18％）患者发生轻微不良反应，根据意向处理分析（ITT）和完成治疗分析（PP），根除率分别为78．79％和83．87％。结论 含左氧氟沙星的四联方案为安全有效的幽门螺杆菌补救治疗方案。     

序贯疗法与标准四联疗法对幽门螺杆菌根除失败后补救治疗的疗效分析

近年经典三联疗法的幽门螺杆菌（11．pylori）根除疗效明显降低,选择有效补救疗法对Hpylori根除失败者有重要意义。目的：比较序贯疗法与标准四联疗法对且pylori根除失败者的疗效。方法：将98例Hpylori根除失败者随机分为序贯疗法组（前5d予奥美拉唑20mg＋阿莫西林1000mgbid,后5d予奥美拉唑20mg＋左氧氟沙星200mg＋克拉霉素500mgbid）和标准四联疗法组（予奥美拉唑20mg＋胶体次枸橼酸铋钾220mg＋阿莫西林1000mg＋克拉霉素500mgbid,疗程7d）。停药4周后复查”C一尿素呼气试验,评估Hpylori根除疗效。结果：共95例患者完成方案,序贯疗法组11Tr和PP分析的Hpylori根除率均显著高于标准四联疗法组（ITF：89．8％对71,4％,PP：91．7％对74。5％,P〈0．05）,序贯疗法组临床症状改善的总有效率亦显著高于标准四联疗法组（95．8％对80．9％,P〈0．05）,两组不良反应发生率无明显差异（P〉0．05）。结论：对Hpylori根除治疗失败的患者,序贯疗法和标准四联疗法均可作为有效的补救治疗方案,但10d序贯疗法的疗效优于7d标准四联疗法。     

十二指肠溃疡患者根除幽门螺杆菌后抑酸维持治疗的疗效研究

背景：对感染幽门螺杆菌（H.pylori）的消化性溃疡患者成功根除且H.ylori后,是否应继续行抑酸治疗,目前尚存在争议。目的：探讨合并H.pylori感染的十二指肠溃疡（DU）患者根除H.pylori后抑酸维持治疗的疗效。方法：112例合并H.pylori感染的DU患者随机分为A组和B组,A组给予10d四联疗法：兰索拉唑30mg＋阿莫西林1g＋克拉霉素0．5gbid＋枸橼酸铋钾110mg qid,疗程10d。B组：在A组方案的基础上,疗程结束后再予兰索拉唑30mg,1次／d,维持4周。治疗结束4周后复查胃镜,评估H.pylori根除疗效、溃疡愈合率和腹痛缓解率。结果：109例患者完成方案。A、B两组按意向治疗（ITT）和按方案（PP）分析的H.pylori根除率（ITT：85．7％对87．5％;PP：88．9％对89．1％）和溃疡愈合率（ITT：87．5％对94．6％;PP：90．7％对96．4％）以及腹痛缓解率（95．6％对95．7％）相比差异均无统计学意义（P〉0．05）。结论：以10d四联疗法根除H.pylori后,可使多数DU患者的溃疡愈合,无需进一步行维持抑酸治疗。     

质子泵抑制剂四联疗法作为幽门螺杆菌根除治疗一线方案的临床研究

背景：随着幽门螺杆菌（H．pylori）对抗生素耐药率的上升，传统一线治疗方案质子泵抑制剂（PPI）三联疗法的根除率逐渐下降。临床上需要新的一线治疗方案以提高H．pylori感染的初治成功率。目的：评价PPI四联1周疗法作为H．pylori根除治疗一线方案的疗效和安全性。方法：符合入选标准的H．pylori感染患者随机分为A1组（LCAB方案：兰索拉唑30mg＋克拉霉素250mg＋阿莫西林1．0g＋枸橼酸铋钾220mg，b．i．d．）、A2组（LCMB方案：兰索拉唑30mg＋克拉霉素250mg＋甲硝唑400mg＋枸橼酸铋钾220mg，b、i．d．）和B1组（LCA方案：兰索拉唑30mg＋克拉霉素500mg＋阿莫西林1、0g，b．i．d．）、B2组（LCM方案：兰索拉唑30mg＋克拉霉素500mg＋甲硝唑400mg，b．i．d、）。各组疗程均为1周。记录治疗期间发生的不良反应。疗程结束4周后以快速尿素酶试验、组织学或^13C-尿素呼气试验判断H．pylori根除情况。结果：共145例患者纳入研究。A组按方案（PP）分析H．pylori根除率显著高于B组（91．9％对79．2％，P〈0．05），意向治疗（ITT）根除率则与B组无显著差异（83．8％对74．0％，P〉0．05）。A1组PP和ITT根除率分别为93．8％和85．7％，A2组分别为90．0％和81．8％；B1组分别为79．4％和75．0％，B2组分别为78．9％和73．2％。A1与A2组比较，B1与B2组比较，差异均无统计学意义（P〉0．05）。各组均未见明显不良反应。结论：PPI四联1周疗法用于H．pylori感染的初治，疗效明显高于PPI三联1周疗法，是一种可供选择的一线治疗方案。     

含加替沙星的四联方案补救治疗幽门螺杆菌的临床观察

[目的]分析含加替沙星的四联疗法补救初次根除治疗幽门螺杆菌(H.pylori,Hp)失败的有效性和安全性.[方法]将133例Hp感染初次根除失败患者随机分为治疗组71例,对照组62例.治疗组给予加替沙星、呋喃唑酮、果胶铋、兰索拉唑治疗,对照组给予甲硝唑、呋喃唑酮、果胶铋、兰索拉唑治疗,疗程均为10 d.停药4周后复查Hp,分析Hp的根除率及不良反应发生率.[结果]治疗组、对照组Hp根除率分别为91.18％、81.67％ (P＜0.05).不良反应发生率治疗组为13.23％,对照组为21.67％,2组间差异有统计学意义(P＜0.05).[结论]含加替沙星的四联方案是治疗Hp初次根除失败后的一种安全、有效的补救治疗方案.     

含铋剂和克拉霉素的四联根除方案在幽门螺杆菌一线治疗中的作用

背景：近年经典三联方案对幽门螺杆菌（H.pylori）感染的根除疗效明显下降,建立新型、安全和高效的一线标准治疗方案是临床工作的当务之急。目的：评估含铋剂和克拉霉素的四联方案作为H.pylori一线治疗方案的疗效和安全性。方法：120例胃镜诊断为非溃疡性消化不良的H.pylori感染患者随机分为3组：7 d三联组（奥美拉唑20 mgbid＋阿莫西林1000 mg bid＋克拉霉素500 mg bid,疗程7 d）、7 d四联组（7 d三联方案＋枸橼酸铋钾220 mg bid,疗程7 d）和2周四联组（方案同7 d四联组,疗程2周）。治疗结束后至少4周行13C-尿素呼气试验以评估根除疗效。H.pylori分离菌株行克拉霉素、甲硝唑和阿莫西林药敏试验。结果：115例患者按方案完成治疗。7 d三联组、7 d四联组和2周四联组按意向治疗（ITT）分析H.pylori根除率分别为70.0%、75.0%和90.0%,按方案（PP）分析分别为73.7%、76.9%和94.7%。2周四联组ITT和PP根除率均显著高于7 d三联组（P〈0.05）,PP根除率显著高于7 d四联组（P=0.026）,而7 d三联组ITT和PP根除率与7 d四联组相比均无明显差异。H.pylori对克拉霉素、甲硝唑和阿莫西林的耐药率分别为24.2%、48.3%和0%,7 d三联组、7 d四联组和2周四联组对克拉霉素耐药菌株的根除率逐渐升高（37.5%、55.6%、80.0%）,但差异无统计学意义。除2周四联组中1例患者因皮肤过敏而未完成治疗外,其余患者的不良反应相似且轻微,耐受性良好。结论：含铋剂和克拉霉素的2周四联方案可明显提高H.pylori根除疗效,且安全性较高,可作为H.pylori一线治疗的标准方案。     

含左氧氟沙星的三联方案补救根除幽门螺杆菌:荟萃分析

目的系统评价含左氧氟沙星的三联方案补救根除幽门螺杆菌的疗效和耐受性。方法检索Medline、Embase、Cinahl，检索词为（Helicobacter pylori或H．pylori）和（levofloxaxin或fluoruquinolones或quinolones），检索中国生物医学文献数据库（CBM-disc），检索词为“幽门螺杆菌和左氧氟沙星”或“幽门螺杆菌和喹诺酮”。筛选比较含左氧氟沙星的三联方案和含铋剂的四联方案的根除幽门螺杆菌补救治疗随机对照试验，进行荟萃分析，进而评价研究质量，提取数据计算根除率和不良反应率。结果共有7项随机对照试验符合入选标准，含左氧氟沙星的10d三联方案Hp根除率高于含铋剂的7d四联方案（86．9％比61.8%，P〈0．01），不良反应率或严重不良反应率低于后者（16．8％比37，1％，P〈0．01；0．41％比12．1％，P〈0．01），耐受性较好。含左氧氟沙星的7d三联方案疗效与含铋剂的7d四联方案相当（71．4％比78．6％，P=0．24）。结论含左氧氟沙星的10d三联方案补救根除的疗效和耐受性均优于含铋剂的7d四联方案。     

以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌疗效比较——一项单中心、随机、开放、平行对照研究

背景：近年质子泵抑制剂（PPI）＋阿莫西林＋克拉霉素标准三联疗法对幽门螺杆菌（H.pylori）的根除率有所降低,PPI＋铋剂＋甲硝唑＋四环素的四联疗法能否成为一线治疗的首选以及适当延长疗程能否提高根除率尚有待明确。目的：比较以泮托拉唑为基础的7d标准三联疗法与7d、10d四联疗法根除H.pylori的疗效。方法：133例非溃疡性消化不良的H.pylori感染患者随机分配至7d三联组（45例,泮托拉唑40mgbid＋阿莫西林1.0gbid＋克拉霉素500mgbid,PAC方案）以及7d、10d四联组（43例和45例,泮托拉唑40mgbid＋枸橼酸铋钾220mgbid＋甲硝唑400mgtid＋四环素750mgbid,PBMT方案）。治疗结束后至少间隔4周行13C-尿素呼气试验复查H.pylori,评估治疗结果。结果：共129例患者按方案完成治疗。三组H.pylori根除率按意图治疗（ITT）分析分别为73.3%、79.1%和88.9%,按方案（PP）分析分别为75.0%、82.9%和90.9%。7dPAC方案的PP根除率显著低于10dPBMT方案（P〈0.05）。除四联组中有2例患者分别因头晕和腹泻而未完成治疗外,其余患者的不良反应相似且均能耐受。结论：在7d标准三联疗法H.pylori根除疗效降低的情况下,含泮托拉唑、铋剂、甲硝唑和四环素的10d四联疗法可考虑作为根除治疗的首选方案。     

Second-line bismuth-containing quadruple therapy for Helicobacter pylori eradication and impact of diabetes

AIM To investigate Helicobacter pylori (H. pylori) eradication rates using second-line bismuth-containing quadruple therapy and to identify predictors of eradication failure.METHODS This study included 636 patients who failed firstline triple therapy and received 7d of bismuthcontaining quadruple therapy between January 2005 and December 2015. We retrospectively demonstrated H. pylori eradication rates with respect to the year of therapy as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 wk after the completion of bismuth-based quadruple therapy: proton pump inhibitor, metronidazole, bismuth, and tetracycline.RESULTS The overall eradication rates by intention-to-treat analysis and per-protocol analysis were 73.9%( 95% CI : 70.1 %- 77.4%) and 94.5% (95% CI : 92.4%-96.5%), respectively. Annual eradication rates from 2005 to 2015 were 100.0%, 92.9%, 100.0%, 100.0%, 100.0%, 97.4%, 100.0%, 93.8%, 84.4%, 98.9%, and 92.5%, respectively, by per-protocol analysis. A multivariate analysis showed that diabetes mellitus (OR=3.99, 95%CI: 1.56-10.20, P=0.004)was associated with H. pylori eradication therapy failure.CONCLUSION The second-line bismuth-containing quadruple therapy for H. pylori infection is still effective in Korea, and diabetes mellitus is suggested to be a risk factor for eradication failure.     

序贯疗法和四联疗法对幽门螺杆菌初治失败患者的疗效评价

目的:评价含左氧氟沙星序贯疗法和含铋剂四联疗法治疗根除失败的幽门螺杆菌感染患者的疗效以及发生的不良反应.方法:将98例经传统标准三联疗法(7 d)根除幽门螺杆菌失败的患者,随机分成治疗组和对照组.治疗组(序贯疗法)方案为前5d雷贝拉唑+左氧氟沙星,后5d雷贝拉唑+克拉霉素+呋喃唑酮,疗程l0d.对照组(四联疗法)方案为...     

Comparison of the effectiveness of quadruple salvage regimen for Helicobacter pylori infection according to the duration of treatment]

BACKGROUND/AIMS: At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. METHODS: The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. RESULTS: One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). CONCLUSIONS: Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.     

The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.     

Efficacy of 14 day OBMT therapy as a second-line treatment for Helicobacter pylori infection]

BACKGROUND/AIMS: As a second-line treatment for H. pylori eradication in the case of first-line OAC (omeprazole, amoxicillin, clarithromycin) treatment failure, a minimum of one-week OBMT quadruple therapy composed of omeprazole, bismuth, metronidazole, tetracycline has been recommended in European countries and one or two weeks in USA. In Korea, one-week OBMT quadruple therapy is recommended for the case of first-line OAC treatment failure. Because H. pylori eradication rate of one-week OBMT therapy in Korea is about 80%, the eradication rate of one week therapy is not satisfactory. We analyzed the effect of two-week second-line OBMT therapy. METHODS: Between June 2002 and June 2003, 107 patients who were H. pylori positive (44 males and 63 females: mean age 51.8 years) after primary eradication therapy received two-week OBMT therapy. Four weeks after completion of therapy, 13C-urea breath test was performed to detect H. pylori. RESULTS: After two weeks of OBMT therapy, eradication was achieved in 103 of 107 patients (96.3%) and in 68 of 71 peptic ulcer patients (95.8%). CONCLUSIONS: Two-week OBMT therapy should be considered as a retreatment regimen with the eradication rate more than 90%.     

Moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori infection

AIM: To assess the efficacy of moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori(H. pylori) eradication.METHODS: Between January 2010 and December 2012,we screened individuals who were prescribed non-bismuth quadruple therapy for H. pylori eradication. Among them,a total of 98 patients who failed non-bismuth quadruple therapy received 1-wk or 2-wk moxifloxacin-containing triple therapy(400 mg moxifloxacin once daily,and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated using the 13C-urea breath test 4 wk later,after treatment completion. The eradication rates were determined by intention-to-treat and per-protocol analyses.RESULTS: In total,60 and 38 patients received 1-wk and 2-wk moxifloxacin-containing triple therapy,respectively. The intention-to-treat and per-protocol eradication rates were 56.7%(95%CI: 45.0-70.0) and 59.6%(95%CI: 46.6-71.7) in the 1-wk group and 76.3%(95%CI: 63.2-89.5) and 80.6%(95%CI: 66.7-91.9) in the 2-wk group(P = 0.048 and 0.036,respectively). All groups had good compliance(95% vs 94.9%). Neither group showed serious adverse events,and the proportions of patients experiencing mild side effects were not significantly different(21.1% vs 13.9%). Clinical factors such as age,sex,alcohol and smoking habits,comorbidities,and presence of gastric or duodenal ulcer did not influence the eradication therapy efficacy. The efficacy of second-line eradication therapy did not differ significantly according to the firstline regimen.CONCLUSION: Two-week moxifloxacin-containing triple therapy showed better efficacy than a 1-wk regimen after non-bismuth quadruple therapy failure.Key words: Helicobacter pylori; Moxifloxacin-based triple; Non-bismuth quadruple; Second-line; Eradication