Long-term outcomes after Helicobacter pylori eradication with second-line, bismuth-containing quadruple therapy in Korea

OBJECTIVES: To determine the long-term outcomes in terms of Helicobacter pylori and ulcer recurrence after second-line eradication with bismuth-containing quadruple regimens in Korea. METHODS: Sixty-seven patients with peptic ulcer disease after successful eradication using second-line quadruple therapies were prospectively followed up 1 month after treatment and then every 6 months or when dyspeptic symptoms reappeared to ascertain H. pylori and ulcer status. RESULTS: Three patients were lost during follow-up. The median duration of follow-up of the remaining 64 patients was 26.8 months. H. pylori recurrence occurred in 11 of these 64 patients (17.2%), giving a calculated reinfection rate of 6.0% per patient-year. Only one of the 11 patients was reinfected by 12 months after treatment completion. Four of 11 patients (36.4%) who became reinfected experienced peptic ulcer recurrence, but none of 53 patients who were not reinfected experienced recurrence. No evidence was obtained to indicate that the reinfection rate depended on the age, sex, ulcer location, or eradication regimens. The relapse of dyspeptic symptoms was the only factor predictive of H. pylori recurrence. CONCLUSION: This study suggests that the recurrence rate of H. pylori at 1 year after second-line, bismuth-containing quadruple therapy is low, but the annual reinfection rate is as high as 6%. Surveillance for H. pylori reinfection facilitating peptic ulcer recurrence may be warranted even after a second eradication, especially when dyspeptic symptoms reappear in Korea.     

幽门螺杆菌感染与上胃肠道疾病

1982年Marshall和Mareen首次从慢性活动性胃炎患者的胃粘膜中分离出为幽门螺杆菌(Hp)。本文概括了Hp与上胃肠道疾病的关系，并评估其感染的治疗。现已确认Hp与4种上胃肠道疾病密切相关：(1)慢性胃炎；(2)消化性溃疡病；(3)胃癌；(4)胃粘膜相关淋巴样组织(MALT)淋巴瘤。Hp是慢性胃炎的主要病因，与消化性溃疡病的发生密切相关，Hp感染增加了胃腺癌发生的危险性，而且也涉及到胃MALT淋巴瘤发生的致病机理。Hp感染的治疗是以PPI、铋制剂以及RBC为基础的三联疗法，当三联疗法失败时则推荐四联疗法。四联疗法是传统的三联疗法(铋剂为基础的三联疗法)十PPI组成。     

Eradication rates of helicobacter pylori infection with second-line treatment: non-ulcer dyspepsia compared to peptic ulcer disease

BACKGROUND/AIMS: Initial proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection is less effective in patients with nonulcer dyspepsia (NUD) than those with peptic ulcer disease (PUD). To date, there have been no studies on the difference in eradication rates in NUD compared to PUD with regard to second-line therapy. Therefore, we retrospectively analyzed the difference in eradication rates of a second-line quadruple therapy for NUD and PUD patients. METHODOLOGY: Between June 2003 and December 2005, patients who failed to respond to initial PPI-based triple therapy, received 7 days of quadruple therapy (PPI b.i.d., bismuth 300mg q.i.d., metronidazole 500mg t.i.d., tetracycline 500mg q.i.d.) as a second-line treatment regimen. Four weeks after the completion of the course of medication, a 13C-urea breath test was performed for detection of H. pylori. RESULTS: A total of 87 patients received second-line quadruple therapy. Of these, 43 patients had NUD and 44 patients had PUD (19 gastric ulcers, 23 duodenal ulcers, 2 both ulcers). The eradication rates were 76.7% (33/43) in the NUD group and 90.9% (40/44) in the PUD group by per-protocol analysis. Therefore, the eradication rates in the NUD group were significantly lower than those in the PUD group (p = 0.034). CONCLUSIONS: A 7-day bismuth-based second-line quadruple therapy for H. pylori infection was less effective in patients with NUD than those with PUD. Therefore, a more potent second-line treatment regimen or extension of treatment duration of quadruple therapy should be considered for the eradication of H. pylori in patients with NUD.     

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%.     

How to proceed in Helicobacter pylori-positive chronic gastritis refractory to first- and second-line eradication therapy

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.     

Helicobacter pylori-related diseases: dyspepsia, ulcers and gastric cancer

This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori infection at Digestive Disease Week 2011. In developed countries, the prevalence of H. pylori infection has decreased, but seems to have reached a plateau at a fairly high level. Antibiotic resistance is increasing in several countries. H. pylori eradication does not contribute to the development of gastroesophageal reflux disease or worsen its course. The frequency of idiopathic peptic ulcers seems to be increasing. H. pylori eradication eliminates almost all episodes of peptic ulcer rebleeding; nevertheless, the use of non-steroidal anti-inflammatory drugs or H. pylori reinfection can lead to bleeding recurrence. H. pylori-negative patients with peptic ulcer bleeding more frequently have bleeding recurrences and higher mortality. In each particular population, there is a close correlation between the prevalence of H. pylori infection and the incidence of gastric cancer. H. pylori eradication is associated with a higher and faster healing rate of ulcerous lesions caused by endoscopic submucosal dissection. In patients undergoing endoscopic submucosal dissection for early gastric cancer, H. pylori eradication decreases the incidence of metachronous tumors. In a high proportion of cases, H. pylori eradication induces MALT lymphoma regression, and long-term tumoral recurrences are exceptional. Narrow-band imaging allows visualization of the mucous and vascular pattern in H. pylori-infected patients during the endoscopic examination. The electrochemical properties of H. pylori allow these lesions to be rapidly and accurately detected in gastric biopsies. The efficacy of "traditional" triple therapies currently leaves much to be desired. The superiority of "sequential" therapy over the standard triple therapy should be confirmed in distinct environments. The "concomitant" quadruple therapy seems to be as effective as "sequential" therapy, but with the advantage of being simpler. Both the "sequential" and the "concomitant" regimens are relatively effective even when clarithromycin resistance is present. Second-line rescue therapy with levofloxacin for 10 days is effective and is simpler and better tolerated than quadruple therapy. In patients allergic to penicillin, a combination with levofloxacin and clarithromycin is a promising rescue alternative. The new-generation quinolones, such as moxifloxacin and sitafloxacin, could be useful as eradication treatment. After two eradication treatment failures, an empirical third-line rescue therapy may be a valid option in clinical practice. Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective.     

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.     

Helicobacter pylori:Effect of coexisting diseases and update on treatment regimens

The presence of concomitant diseases is an independentpredictive factor for non-Helicobacter pylori(H. pylori) peptic ulcers. Patients contracting concomitant diseases have an increased risk of developing ulcer disease through pathogenic mechanisms distinct from those of H. pylori infections. Factors other than H. pylori seem critical in peptic ulcer recurrence in end stage renal disease(ESRD) and cirrhotic patients. However, early H. pylori eradication is associated with a reduced risk of recurrent complicated peptic ulcers in patients with ESRD and liver cirrhosis. Resistances to triple therapy are currently detected using culture-based and molecular methods. Culture susceptibility testing before first- or second-line therapy is unadvisable. Using highly effective empiric first-line and rescue regimens can yield acceptable results. Sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance. Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective in patients with dual-(clarithromycin- and metronidazole-) resistant H. pylori strains. We aim to review the prevalence of and eradication therapy for H. pylori infection in patients with ESRD and cirrhosis. Moreover, we summarized the updated H. pylori eradication regimens.     

含多西环素的四联方案补救治疗幽门螺杆菌初次根除失败的临床研究

幽门螺杆菌（H．pylori）一线三联疗法的根除失败率日益增高。目的：评价含多西环素的四联方案补救治疗H．pylori初次根除失败的有效性和安全性。方法：共纳入37例日．pyZo打初次根除失败的消化性溃疡、慢性萎缩性胃炎或非溃疡性消化不良患者,予四联方案埃索美拉唑（20rag）＋枸橼酸铋钾（220mg）＋多西环素（100mg）＋阿莫西林（1000mg）,2次／dx10d。治疗结束4周后行”^13C-尿素呼气试验（UBT）以评估H．pylori根除情况。结果：4例患者失访,25例患者补救治疗成功,8例失败,补救治疗意向治疗（ITT）分析和符合方案（PP）分析根除率分别为67．6％和75．8％。21例（63．6％）患者发生轻微不良反应。结论：含多西环素的四联方案是一种安全、有效的H．pylori初次根除失败后的补救治疗方案。     

V Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.     

Effectiveness of triple therapy and quadruple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.     

Second Asia–Pacific Consensus Guidelines for Helicobacter pylori infection

The Asia–Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.     

Effects of killing Helicobacter pyloriquadruple therapy on peptic ulcer： A randomized double-blind clinical trial

AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers (PU). METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A: lansoprazole 30 mg qd, plus clarithromycin 250 mg bid, plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3) placebo(group C: gastropine 3 tablets bid for 4 wk). H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years. RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs20% and 0%, respectively,P<0.005), but there was no significant difference compared to those in group A (88% and 92%, P>0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P<0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%,P<0.01). CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.     

4-day triple therapy with rabeprazole, amoxicillin and clarithromycin in the eradication of Helicobacter pylori in patients with peptic ulcer disease--A pilot study

BACKGROUND: It is well established that a 7-day triple therapy achieves eradication rates of Helicobacter pylori between 90% and 95%. Due to a lack of highly effective short-term eradication studies the aim of the present pilot study was to investigate the effect of a 4-day triple therapy with the new proton pump inhibitor rabeprazole (20 mg b. i. d.) in combination with clarithromycin (500 mg b. i. d.) and amoxicillin (1 g b. i. d.) without acid-suppressive pre-treatment in patients with H. pylori-related peptic ulcer disease. METHODS: 20 patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric ulcer: n = 5; duodenal ulcer: n = 9; combined gastric and duodenal ulcer: n = 2, gastric or duodenal ulcer scars: n = 4) and H. pylori infection were consecutively recruited. The Helicobacter pylori status was assessed by means of histology, CLO (urea-) test and C13-urea breath test (C13-UBT) at entry. Treatment success was determined by C13-UBT 35-42 days after end of treatment. RESULTS: In 18 out of the 20 patients (90%) [77-100%, 95%-CI] a negative test result was found in C13-UBT 35-42 days after treatment. The 2 patients who remained H. pylori-positive had a duodenal ulcer. CONCLUSION: A 4-day triple therapy of rabeprazole in combination with clarithromycin and amoxicillin seems to be highly effective in eradicating H. pylori and well tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication rate of 90% is comparable with the established 7-day triple therapy regimens. On the basis of these results and considering costs, side effects and compliance a large number of patients should be enrolled in a confirmatory 4-day eradication trial.     

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.     

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.     

Eradication rate of first-line and second-line therapy for Helicobacter pylori infection, and reinfection rate after successful eradication]

BACKGROUND/AIMS: The increasing trend of antibiotic resistance emphasizes the need for the assessment of eradication rate of first and second-line therapy for Helicobacter pylori (H. pylori) infection. The reinfection rate depends on the geographical, national, or socioeconomic status of the patients. The aim of this study was to evaluate the recent 5-year changes of eradication rates and the reinfection rates after the successful eradication of Helicobacter pylori infection for 3-years follow-up in Bucheon, Korea. METHODS: From February 2001 to August 2006, 3,267 patients with H. pylori-positive peptic ulcer disease received the first-line therapy for 7 days. The 317 patients who failed to the first-line therapy received the second-line therapy for 7 days. The 167 patients with 3-years follow-up after the successful eradication were included. 13C-urea breath tests or rapid urease tests and histologies were assessed to determine the H. pylori status after the eradication. RESULTS: The eradication rate of first-line therapy was 83.7% in 2001, 83.4% in 2002, 83.7% in 2003, 85.9% in 2004, 87.2% in 2005, and 81.8% in 2006 by per protocol analysis (PP), respectively. The eradication rate of second-line therapy was 80.0% in 2002, 86.8% in 2003, 89.7% in 2004, 98.0% in 2005, and 78.8% in 2006 by PP. The cumulative reinfection rate was 6.0%. The annual reinfection rate was 2.0%. The recurrence rate of peptic ulcer was 17.2% in the patients without reinfection and 50% with reinfection. CONCLUSIONS: The eradication rate for H. pylori have not changed in the recent 5-years. The annual reinfection rate was low. The successful eradication of H. pylori was effective for preventing the recurrence of peptic ulcers.     

Helicobacter pylori therapy: first-line options and rescue regimen

In the present paper, several points regarding Helicobacter pylori treatment are reviewed, with the following conclusions: (1) all different proton pump inhibitors (PPIs) are equivalent when prescribed with antibiotics; (2) ranitidine bismuth citrate is equal to or, in some cases with antibiotic resistance, more effective than PPI; (3) previous treatment with PPI does not seem to affect the rate of eradication obtained with PPI plus two antibiotics; (4) just 1 week of PPI is enough to obtain duodenal ulcer healing, provided that H. pylori eradication is achieved; (5) the eradication rates seem to be higher in peptic ulcer than in nonulcer dyspepsia; (6) in areas where the prevalence of metronidazole resistance is high, triple therapy including a PPI, clarithromycin, and amoxicillin is the best option, and (7) quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) is the recommended second-line therapy after PPI-clarithromycin-amoxicillin failure, although replacing the PPI and the bismuth compound by ranitidine bismuth citrate achieves also good results.     

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     

'Rescue' therapies for the management of Helicobacter pylori infection

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7-14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient's compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10-14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.