Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori eradication

AIM: To determine the efficacy of two quintupleregimens for eradication of Helicobacter pylori(H. pylori) in patients who failed previous therapies.METHODS: This prospective, open-label, randomized controlled trial was a phase Ⅱ study conducted from April 2011 to March 2012 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia who failed previous H. pylori eradication with a ten-day quadruple therapy were enrolled. A random block method was used to assign patients to one of two treatment groups. Patients in the first group were treated with 240 mg bismuth subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500 mg tinidazole(BOACT group). Patients in the second group received a regimen containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500 mg metronidazole and 200 mg ofloxacin(BOTMO group). Both regimens were given twice daily for a duration of seven days. The eradication was confirmed by a 14 C urea breath test 12 wk after completion of therapy. Patient compliance and drug side effects were evaluated at the end of the treatment period. The success rates were calculated by intention-to-treat and per-protocol analyses.RESULTS: A total of 205 patients completed the course of treatment, with three patients excluded due to drug intolerance. The mean age of patients did not differ between the BOACT and BOTMO groups(41.6 ± 12.2 years vs 39.6 ± 11.8 years), and no significant differences were found between the two groups in terms of age, sex, smoking habits or the initial eradication regimen. The intention-to-treat and perprotocol eradication rates were significantly higher in the BOTMO group(86.5%, 95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the BOACT group(75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively)(P 0.05). Univariate analyses for both groups did not show any association of sex, smoking and initial therapeutic regimen witheradiation rate(P 0.05 for all). Significantly more patients experienced side effects in the BOACT group compared to the BOTMO group(77.4% vs 36.6%, P 0.01). This difference was exemplified by increases in headache and taste disturbance(P 0.05).CONCLUSION: Quintuple therapy with a BOTMO regimen is an alternative second-line rescue therapy for Iranian patients with failed first-line eradication treatment of H. pylori.     

序贯疗法补救根除幽门螺杆菌感染的疗效观察

目的比较序贯疗法与传统四联疗法对幽门螺杆菌(H.pylori)根除失败后补救治疗的临床疗效。方法选取胃镜下H.pylori快速尿素酶试验或14C尿素呼气试验阳性的患者,经我国标准H.pylori一线三联根除方案治疗7天,停药4周后检测H.pylori,结果仍为阳性者判定为H.pylori根治失败,即进行H.pylori的补救根除治疗,共68例患者入选。随机分为两组:治疗组予以序贯疗法:前5天口服埃索美拉唑20mg和阿莫西林1000mg,2次/d,后5天口服埃索美拉唑20mg、克拉霉素500mg和甲硝唑400mg,2次/d;对照组予以传统四联疗法:口服埃索美拉唑20mg、阿莫西林1000mg、呋喃唑酮100mg和胶体果胶铋100mg,2次/d,疗程7天。疗程结束后4周行14C尿素呼气试验检测H.pylori。结果疗程结束后4周,治疗组H.pylori根除率为93.9%,对照组H.pylori根除率为73.3%,两组H.pylori根除率比较有显著性差异(P0.05)。结论序贯疗法对H.pylori的根除率高于传统四联疗法,可作为有效的H.pylori补救根除治疗方案。     

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。     

左氧氟沙星三联方案与常规四联补救方案治疗幽门螺杆菌感染的荟萃分析

目的:系统性评价含左氧氟沙星的三联方案与常规四联补救方案治疗幽门螺杆菌(H pylori)感染的疗效和不良反应发生率.方法:从常用电子数据库检索含左氧氟沙星的三联方案与四联补救方案根除H pylori的随机临床试验,荟萃分析各项研究的根除率和不良反应发生率的合并OR值;进行敏感性分析;以漏斗图检测发表偏倚.结果:共13项随机临床试验(1181例)符合纳入标准.含左氧氟沙星的三联方案和四联补救方案按意向治疗(ITT)分析的H pylori的根除率分别为77.5%(95%CI 74.1%-80.9%)和70.5%(95%CI 66.8%-74.2%),合并OR值为1.51(95%CI 0.91-2.53);总不良反应发生率分别为21.3%(95%CI 17.7%-24.9%)和36.0%(95%CI 31.8%-40.2%),合并OR值0.45(95%CI 0.29-0.71). 结论:含左氧氟沙星的三联方案具有与常规四联补救方案相似的根除H pylori 疗效,而且可以显著降低根除过程中的不良反应发生率     

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.     

喹诺酮类抗生素一线根除幽门螺杆菌研究现状

幽门螺杆菌(Hp)对甲硝唑或克拉霉素耐药率的不断升高是导致根除失败的主要原因。目前喹诺酮类在根除Hp治疗中的作用已受到重视。本文拟就第三代和第四代喹诺酮类药物左氧氟沙星和莫西沙星在一线根除Hp中的作用作一综述。     

Helicobacter pylori first-line treatment and rescue option containing levofloxacin in patients allergic to penicillin

AimTo assess the efficacy and tolerability of Helicobacter pylori first-line treatment (omeprazole–clarithromycin–metronidazole) and second-line rescue option (omeprazole–clarithromycin–levofloxacin) in patients allergic to penicillin.MethodsPatients: Prospective multicenter study including consecutive patients allergic to penicillin. Therapy regimens: First-line treatment (50 patients): Omeprazole (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and metronidazole (500 mg b.i.d.) for 7 days. Second-line treatment (15 therapy failures out of the aforementioned 50 patients): Omeprazole (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and levofloxacin (500 mg b.i.d.) for 10 days. Outcome variable: Negative ¹³C-urea breath test 8 weeks after completion of treatment.Results(1) First-line treatment (omeprazole–clarithromycin–metronidazole): Per-protocol and intention-to-treat eradication rates were 55% (27/49; 95%CI = 40–70%) and 54% (27/50; 95%CI = 39–69%). Compliance with treatment and follow-up was complete in 98% of cases (one patient was not compliant due to nausea). Adverse events were reported in 5 patients (10%): 4 nausea, 1 diarrhoea. (2) Second-line treatment (omeprazole–clarithromycin–levofloxacin): Per-protocol and intention-to-treat eradication rates were both 73% (11/15; 95%CI = 45–92%). Compliance with treatment and follow-up was complete in all the cases. Adverse events were reported in 4 patients (20%), which did not prevent the completion of treatment: Mild nausea (2 patients), and vomiting and myalgias/arthralgias (1 patient).ConclusionIn H. pylori infected patients allergic to penicillin, the generally recommended first-line treatment with omeprazole, clarithromycin and metronidazole has low efficacy for curing the infection. On the other hand, a levofloxacin-containing regimen (together with omeprazole and clarithromycin) represents an encouraging second-line alternative in the presence of penicillin allergy.     

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.     

Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori eradication

BACKGROUND:  The standard first-line therapies for Helicobacter pylori eradication are based on clarithromycin and amoxicillin or metronidazole. Recent studies suggested levofloxacin as an alternative option for both first-and second-line H. pylori eradication treatment.
AIMS:  To compare efficacy and tolerability of two different 7-day standard triple therapies versus 7-day levofloxacin-based triple therapy in first-line treatment for H. pylori infection.
METHODS:  Three hundred consecutive H. pylori positive patients were randomized to receive: clarithromycin, amoxicillin, esomeprazole (Group A: N = 100); clarithromycin, metronidazole, esomeprazole (Group B: N = 100); or clarithromycin, levofloxacin, esomeprazole (Group C: N = 100). H. pylori status was rechecked by ¹³C urea breath test 6 wk after the end of therapy.
RESULTS:  Sixteen out of 300 patients discontinued treatment because of the occurrence of side effects (Group A, 5; Group B, 7; Group C, 4). The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 75% and 79%; Group B, 72% and 77.4%; and Group C, 87% and 90.6%. The eradication rate achieved with levofloxacin-based triple therapy was significantly higher than that with standard therapies in either ITT (87% vs 75%, p <0.05; 87% vs 72%, p <0.01;) or PP analysis (90.6% vs 79%, p <0.05; 90.6 vs 77.4, p <0.05). No difference was found between standard triple therapies. The incidence of side effects was similar among groups.
CONCLUSIONS:  A 7-day levofloxacin-based triple therapy can achieve higher H. pylori eradication rates than standard regimens. These data suggest levofloxacin-based regimens can be the most effective in first-line anti- H. pylori therapy, at least in the Italian population.     

Helicobacter pylori infection: treatment options

After two decades of progress the best current approach to treatment of Helicobacter pylori infection is a strategy that combines two consecutive complementary treatments. Current guidelines recommend a first-line triple therapy - 7-10 days of a proton-pump inhibitor (PPI), clarithromycin and amoxicillin - followed by a quadruple therapy combining a PPI, metronidazole, tetracycline and a bismuth salt for treatment failures. Regrettably, present cure rates for first-line triple therapy are below 80%, and many patients require second-line treatment with further testing and control visits. Although most compliant patients are cured by the second-line treatment, patients often do not complete the full process and, as a result, final cure rates for the whole strategy often fall below 90%. This means that more effective first-line therapies are required. Promising recent developments include using quadruple therapy as first-line therapy, the use of adjuvant lactoferrin with triple therapy and a newly devised combination of a PPI, clarithromycin, amoxicillin and metronidazole, known as sequential treatment. Additional future developments will require the incorporation of new antibiotic weapons in the anti-H. pylori arsenal. The new quinolones and rifamycin derivates have recently demonstrated their efficacy in the treatment of H. pylori infection.     

Helicobacter pylori screening: options and challenges

Helicobacter pylori gastritis is the most frequent infectious disease in the gastrointestinal tract. Clinical sequelae of the infection including peptic ulcer disease, sporadic gastric cancer (GC) and primary B-cell gastric lymphoma (MALT-lymphoma) may develop in up to 20% of the infected individuals. The H. pylori screen-and-treat strategy is addressed to members of communities with high GC incidence, and first-degree relatives of GC patients. For primary GC prevention, H. pylori screen-and-treat is most effective in patients without precancerous conditions. In populations at moderate risk, strategies for GC prevention need to be explored. A special clinical scenario for primary and secondary prevention of H. pylori related benign complications are patients on non-steroidal anti-inflammatory drugs and low-dose aspirin. Vaccination represents another option for eliminating H. pylori infection in the population and a new H. pylori vaccine has shown promising results. However, long-term effects with the use of vaccine are not available.     

Lansoprazole-based sequential and concomitant therapy for the first-line Helicobacter pylori eradication

OBJECTIVE: The aim of this prospective study was to compare the efficacy of the first‐line lansoprazole‐based sequential therapy and concomitant therapy (lansoprazole, amoxicillin, clarithromycin and metronidazole) for Helicobacter pylori (H. pylori) eradication. METHODS: A total of 169 patients with H. pylori infection were randomly assigned to either the sequential therapy group (n = 85) or the concomitant therapy group (n = 84). A follow‐up endoscopy or urea breath test was examined at least 12 weeks after eradication. RESULTS: Comparable H. pylori eradication rate was observed in both the sequential therapy and concomitant therapy groups by either intention‐to‐treat analysis [sequential 80.0% (68/85) vs concomitant 88.1% (74/84); P = 0.27] or per protocol analysis [sequential, 85.3% (64/75) vs concomitant, 94.6% (70/74); P = 0.60]. Adverse effects were reported and good compliance was observed in both groups (P = 0.72). Although dual antibiotics resistance affected the therapeutic efficacy of sequential therapy (P = 0.03), not concomitant therapy (P = 0.74), it was not an independent factor for predicting the treatment outcome. CONCLUSION: First‐line lansoprazole‐based sequential and concomitant therapy were well‐tolerated and comparable in terms of their H. pylori eradication rate.     

The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis

BACKGROUND: Standard triple therapies are the most used treatment in clinical practice. However, a critical fall in the H pylori eradication rate following these therapies has been observed in the last few years. The sequential regimen is a novel, promising therapeutic approach. OBJECTIVES: To evaluate the available data on the sequential therapy regimen. METHODS: A pooled-data analysis of all studies on the sequential regimen was performed. The eradication rate was calculated according to gastroduodenal pathology, proton pump inhibitor used, antibiotic resistance, as well as setting (paediatric or geriatric patients). Compliance, side effects, and cost implications were also evaluated. RESULTS: Overall, more than 1800 patients have been treated with the sequential regimen. Such a therapy was superior to 7-10 days triple therapies in paediatric, adult and elderly patients, achieving an eradication rate constantly higher than 90% at ITT analysis. Although primary clarithromycin resistance reduced the efficacy of such a therapy, a success rate significantly higher than that observed with the standard 7-10 days triple therapies was found. CONCLUSION: The 10-day sequential treatment regimen achieves higher eradication rates than standard triple therapies.     

四联疗法与序贯疗法在幽门螺杆菌根除补救治疗中的疗效比较

[目的]比较四联疗法与序贯疗法在幽门螺杆菌(Hp)根除补救治疗中的疗效及安全性,旨在寻找一种有效、安全、经济的补救治疗方案。[方法]将首次根除Hp治疗失败的90例慢性胃炎患者,随机分为四联疗法组和序贯疗法组,每组45例。四联疗法组患者治疗方案为埃索美拉唑、枸橼酸铋钾、阿莫西林、莫西沙星,疗程14d。序贯疗法组患者治疗方案为前5d给予埃索美拉唑、阿莫西林;后5d给予埃索美拉唑、克拉霉素、奥硝唑。所有患者在疗程结束停药4周后行14 C尿素呼气试验检测Hp。比较2组患者治疗前后的不良反应。[结果]四联疗法组Hp根除率(91.1%)显著高于序贯疗法组(75.6%),差异有统计学意义(P<0.05)。2组不良反应均很轻微,组间不良反应发生率比较差异无统计学意义(P>0.05)。[结论]对于Hp补救治疗,四联疗法较序贯疗法疗效更好,且不良反应小,患者依从性好,值得在临床上推广。     

Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication

AIM: To evaluate the efficacy of moxifloxacin-based sequential therapy(MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori(H. pylori) infection.METHODS: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST(MBST group, n = 140) or hybrid(Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated.RESULTS: The eradication rates in the intention-totreat(ITT) analysis were 91.4%(128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2%(114/144; 95%CI: 77.3%-80.7%) in the Hybrid group(P = 0.013). The eradication rates in the perprotocol(PP) analysis were 94.1%(128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6%(114/138; 95%CI: 80.6%-84.1%) in the Hybrid group(P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT(P = 0.013) and the PP analyses(P = 0.003). Both groups exhibited full compliance with treatment(MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8%(16/136) and 19.6%(27/138) in the MBST and Hybrid group, respectively(P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group.CONCLUSION: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.     

Quadruple therapy with moxifloxacin and bismuth for first-line treatment of Helicobacter pylori

AIM: To compare triple therapy vs quadruple therapy for 10 d as first-line treatment of Helicobacter pylori (H. pylori) infection.METHODS: Consecutive H. pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole (PAN) 20 mg bid, amoxicillin (AMO) 1 g bid and moxifloxacin (MOX) 400 mg bid for 10 d (PAM) or with quadruple therapy of PAN 20 mg bid, AMO 1 g bid, MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d (PAMB). All patients were found positive at 13 C-Urea breath test (UBT) performed within ten days prior to the start of the study. A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment. χ² analysis was used for statistical comparison. Per protocol (PP) and intention-to-treat (ITT) values were also calculated.RESULTS: Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group. One patient in each group did not return for further assessment. Eradication was higher in the PAMB group (negative: 46 and positive: 3) vs the PAM group (negative: 44 and positive: 12). The H. pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group, both with the PP and ITT analyses (PP: PAMB 93.8%, PAM 78.5%, P < 0.02; ITT: PAMB 92%, PAM 77.1 %, P <0.03).CONCLUSION: The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H. pylori shows a high resistance to fluoroquinolones.