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.     

Efficacy of quadruple therapy for Helicobacter pylori eradication after failure of proton pump inhibitor‐based triple therapy in Singapore

BACKGROUND: Helicobacter pylori eradication is the mainstay in the treatment of H. pylori‐associated peptic ulcer disease. Current standard eradication therapy consists of 1 week of treatment with a proton pump inhibitor (PPI) and two antibiotics selected from amoxicillin, metronidazole and clarithromycin. In this study we aimed to assess the efficacy of quadruple therapy consisting of a PPI, bismuth, tetra‐cycline and metronidazole in patients for whom initial H. pylori eradication using a triple therapy regimen consisting of a PPI, amoxicillin and clarithromycin was unsuccessful. METHODS: Consecutive patients with H. pylori‐associated peptic ulcer disease, in whom H. pylori with triple therapy had been unsuccessful, were included in the study. These patients had been treated with a regimen that included a PPI (standard dose twice daily), amoxicillin (1 g twice daily) and clarithro­mycin (500 mg twice daily) for 1 week during 1997?2001. Diagnosis of peptic ulcer disease was made at esophagogastroduodenoscopy. Helicobacter pylori infection was considered to be present on the basis of either a positive rapid urease test, positive histo­logical identification of H. pylori or both. Failure of initial H. pylori eradication was established with either a rapid urease test, a ¹³C urea breath test or histology. Quadruple therapy consisted of a PPI (standard dose twice daily), metronidazole (400 mg three times daily), tetracycline (500 mg four times daily) and bismuth subcitrate (240 mg twice daily). Failure of quadruple therapy was diagnosed on the basis of a positive ¹³C urea breath test. RESULTS: Fifty‐three patients received quadruple therapy. The median age was 52 years (range 20?74) and the male to female ratio was 42 : 11. On an intent‐to‐treat basis, the eradication rate was 69.8%, whereas on a per‐protocol basis, the eradication rate was 82.2%. CONCLUSION: We conclude that a 1‐week quadruple therapy regime consisting of a PPI, bismuth, tetracycline and metronidazole was effective in 82.2% of patients who experienced an unsuccessful initial H. pylori eradication attempt with PPI, amoxicillin and clarithromycin.     

Update on therapeutic options for <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-related diseases

Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) has been recommended as the treatment of choice for Helicobacter pylori eradication. This regimen is now challenged by an increasing level of clarithromycin resistance that jeopardizes the treatment success. When clarithromycin resistance has been detected, or when its rate is known to be high in the geographic area, this drug cannot be used. It can be replaced by metronidazole, the resistance of which has a limited clinical relevance. Another option is to prescribe tetracycline and metronidazole with a PPI or ranitidine bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be used in combination with amoxicillin and a PPI. Probiotics can be added to all of these regimens to improve compliance by decreasing adverse events. But some authors advocate a quadruple therapy as a first-line treatment. Solutions to improve the limitations of this last regimen are now being proposed. Clarification of the controversial treatment indications such as gastroesophageal reflux disease or prevention of nonsteroidal anti-inflammatory drug gastroduodenal symptoms has been made. The question of prevention of gastric carcinoma by H. pylori eradication remains unanswered.     

Helicobacter pylori: From art to a science

Helicobacter pylori infection is widely prevalent especially in developing countries. Increasing knowledge of the pathophysiology associated with H. pylori is leading to an understanding of the mechanisms of mucosal inflammation and gastritis and how this leads to peptic ulcer disease, gastric mucosal associated lymphoid tissues (MALT), lymphoma and gastric cancer. More accurate diagnostic testing for the infection is now possible with both endoscopic and non-endoscopic tests to identify patients most appropriate for eradication therapy. Modern treatments tend to overcome the problems of metronidazole resistance and compliance seen with two week bismuth triple therapy and widely studied is a proton pump inhibitor given with clarithromycin and amoxicillin or metronidazole for one week. These achieve amongst the highest eradication rates and have also been shown to be cost effective. This paper reviews these recent advances and addresses areas of clinical interest and future directions.     

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.     

Comparison of short- and long-term treatment protocols and the results of second-line quadruple therapy in children with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

BACKGROUND: Research regarding the optimal therapeutic approach to Helicobacter pylori infection in children is ongoing. There is no consensus as to duration of treatment or second-line therapy. The purpose of this study was compare the efficacy of 7-day and 14-day triple therapies and report the results of second-line quadruple therapy in children. METHODS: A total of 275 consecutive H. pylori-infected patients were enrolled into two groups. Group 1 (n = 180) received triple therapy with 14 days of amoxicillin and clarithromycin and 21 days of proton pump inhibitor. Group 2 (n = 95) received triple therapy including 7 days of amoxicillin and clarithromycin with 21 days of proton pump inhibitor. Subsequently, 89 patients not responding to the triple therapies received quadruple therapy comprising omeprazole (14 days), bismuth subcitrate (7 days), doxycycline (7 days), and metronidazole (7 days). Eradication was evaluated by 13C-urea breath test. RESULTS: The per-protocol eradication rates in groups 1 and 2 were 60.5% and 55.8%, respectively (P = 0.44). In the second interview with 227 patients, severe symptoms were reported to have disappeared in 59% and decreased notably in 34.8%. Helicobacter pylori was eradicated in 66.7% of patients at the end of the quadruple therapy. In the third interview with 75 patients, severe symptoms had decreased in 38.6% and disappeared in 56%. CONCLUSIONS: The different duration of the two treatment regimens had no impact on eradication rates. Furthermore, quadruple therapy was necessary to achieve H. pylori eradication after triple therapy. However, the eradication rate with quadruple therapy was still insufficient. Consequently, a new therapeutic approach to H. pylori infection in children is needed.     

Helicobacter pylori:Management in 2013

Helicobacter pylori(H.pylori)is a prevalent,worldwide,chronic infection.Choice of treatment can be modified according to antibiotic-resistance rates of H.pylori.The ideal therapeutic regimen for H.pylori infection should achieve an eradication rate of≥80%.In some countries,triple therapy with a proton-pump inhibitor(PPI),clarithromycin,and amoxicillin or metronidazole is still the best option.Bismuth-containing quadruple therapy consisting of bismuth salts,tetracycline,metronidazole and PPI,may be the preferred option in countries with clarithromycin resistance>20%.Sequential therapy including a PPI and amoxicillin given for the first 5 d,followed by triple therapy including a PPI,clarithromycin,and nitroimidazole antimicrobial(all twice daily)for the remaining 5 d,can be another option for the first-line treatment of H.pylori.Recent data suggest that treatment with PPI,levofloxacin,and amoxicillin for 10 d is a good choice for second-line therapy.Concomitant therapy consisting of PPI,amoxicillin,clarithromycin and metronidazole is another option for second-line treatment.If second-line treatment also fails,it is recommended to culture H.pylori from biopsy specimens and perform antimicrobial susceptibility testing.Rescue treatment should be based on antimicrobial susceptibility.     

Treatment of Helicobacter pylori infection:Current status and future concepts

Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated lymphoid-tissue lymphoma.Although alternative therapies,including phytomedicines and probiotics,have been used to improve eradication,current treatment still relies on a combination of antimicrobial agents,such as amoxicillin,clarithromycin,metronidazole,and levofloxacin,and antisecretory agents,such as proton pump inhibitors(PPIs).A standard triple therapy consisting of a PPI and two antibiotics(clarithromycin and amoxicillin/metronidazole)is widely used as the first-line regimen for treatment of infection,but the increased resistance of H.pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy.Alternatively,levofloxacin-based triple therapy can be used as rescue therapy for H.pylori infection after failure of first-line therapy.The increase in resistance to antibiotics,including levofloxacin,may limit the applicability of such regimens.However,since resistance of H.pylori to amoxicillin is generally low,an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy.In addition,the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H.pylori infection,though its efficacy needs to be verified in clinical studies.     

Evaluation of triple and quadruple Helicobacter pylori eradication therapies in Iranian children: a randomized clinical trial

BACKGROUND: Clinical trials in children concerning Helicobacter pylori eradication treatments are scarce. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapy using PPI, amoxicillin and clarithromycin in Iranian children. We also evaluated the efficacy of quadruple therapy with PPI, metronidazole, amoxicilin and bismuth citrate in Iranian children. METHODS: This was a randomized clinical trial performed in Emam Khomeini Hospital between 2003 and 2004. Patients with confirmed H. pylori infection by histology were divided into two groups in a randomized 1:1 scheme: the triple regimen group (omeprazole, clarithromycin and amoxicillin for 10 days) and the quadruple regimen group (omeprazole, amoxicillin, metronidazole and bismuth citrate for 10 days). The eradication was assessed by the C-urea breath test 4 weeks after the end of treatment and analyzed by per-protocol and intention-to-treat approaches. RESULTS: One hundred and twenty-two patients (mean age 12.36+/-3.06 years) were entered into the study. Only 100 patients completed the study (50 patients in each regimen group). The eradication rates by triple therapy were 92% and 75.5% for the "per-protocol" and "intention-to-treat" approaches, respectively. In the quadruple regimen group, the eradication rates were 84% by the per-protocol approach and 68.8% in the intention-to-treat approach. Symptom responses to therapy were reported in all patients with successful eradication (88% of all patients). CONCLUSION: With regard to recent recommendations, we also suggest PPI, amoxicillin and clarithromycin triple therapy as a first-line eradication treatment, and quadruple therapies as a second-line option, in Iranian children.     

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.     

Treatment of Helicobacter pylori infection]

Significant progress and new insights have been gained since Helicobacter pylori was found in 1982. Even with currently most effective treatment regimen, about 10-20% of patients will fail to obtain the eradication of H. pylori infection. This review will focus on the empirical treatment for H. pylori infection in Korea. Seven days triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) has been the main first line therapy for H. pylori infection in Korea after the recommendation by Korean H. pylori study group in 1998. Such triple therapy has been the effective regimen for eradication of H. pylori infection. However, the efficacy of 7 days proton pump inhibitor-amoxicillin-clarithromycin therapy becomes lower and various eradication rates probably reflects the increase in antimicrobial resistance, recently. The recent multi-center prospective randomized study and meta-analysis showed 14 days proton pump inhibitor-amoxicillin-clarithromycin therapy is more effective than 7 days or 10 days therapy. In the case of failure, quadruple therapy (proton pump inhibitor, a bismuth salt, metronidazole and tetracycline) is a very effective second-line regimen. After the failure of two or more eradication treatments, bacterial resistance to antibiotics should be evaluated and the regimen of third-line therapy should be selected according to each antimicrobial susceptibility. The empirical third-line therapies, recommended in the cases that antimicrobial susceptibility test is unavailable, are unclear of its validity at present in Korea. The triple therapies including rifabutin, moxifloxacin, or levofloxacin or dual therapy including high dose proton pump inhibitor and amoxicillin are needed to be proven as possible candidates for the empirical third-line therapy. Multiple eradication failures should be handled on a case-by-case basis by specialists.     

Treatment of Helicobacter pylori

Triple therapy, consisting of two antibiotics, clarithomycin and amoxicillin or metronidazole in combination with a proton pump inhibitor (PPI) has become the first-line option for infection with Helicobacter pylori and has been recommended at several consensus conferences. In clinical practice, approximately 20% of patients will fail to obtain H. pylori eradication with the recommended treatment regimens. Major causes of treatment failure are insufficient patient compliance and antibiotic resistance. Because of antibiotic resistance, bismuth-based quadruple therapy has also become a first-line regimen in areas with exceedingly high rates of clarithromycin and metronidazole resistance, and is the preferred second-line option otherwise. Triple therapies based on levofloxacin and/or rifabutin mainly with combination of amoxicillin are options if multiple eradication failure occurs. However, following therapy failure beyond a second treatment attempt requires antibiotic resistance testing. New drugs and adjuvant agents have been reported but their efficacy needs further evaluation.     

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。     

Comparison of three different second-line quadruple therapies including bismuth subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate Helicobacter pylori with a 14-day standard first-line therapy

Background and Aim: Many studies have reported poor results with standard first‐line treatment for Helicobacter pylori. Second‐line regimens that may overcome bacterial resistance can minimize side‐effects and optimize compliance. The aim of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and bismuth subcitrate‐based quadruple therapy, after failure of a PPI plus clarithromycin and amoxicillin as first‐line therapy. Methods: Patients who failed to eradicate the infection after initial therapy were randomly separated into three groups. The first group received lansoprazole, bismuth subcitrate, metronidazole and amoxicillin (LBMA); in the second group metronidazole was replaced by tetracycline (LBTA); and the third group was given metronidazole and tetracycline in addition to same doses of lansoprazole and bismuth subcitrate (LBMT). Results: In the LBMA group, the eradication rate was 74.7% and was significantly related to sex, with no relationship to age. In the LBTA group the eradication rate was 81.5% with similar rates in males and females. No relation to sex or age was observed. In the LBMT group the eradication rate was 82.1% with no difference between women and men and it was not related to age, either. Eradication rates in study groups were similar (P > 0.05). Conclusion: A‐14‐day regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline–amoxicillin and tetracycline–metronidazole, is an effective quadruple therapy after one failed course of standard triple therapy. The evaluation of tolerability of and compliance with quadruple therapy needs further studies.     

Antibiotic treatment for Helicobacter pylori : Is the end coming?

Infection with the Gram-negative pathogen Helicobacter pylori(H. pylori) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a groupI carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacil us. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.     

An alternative salvage regimen for Helicobacter pylori-resistant patients with heart failure

Helicobacter pylori infects over 50% of the worldwide population. For eradication, European, Canadian, and American guidelines recommend a regimen consisting of a proton pump inhibitor, clarithromycin, and metronidazole or amoxicillin dosed twice daily for at least 7 days. When this treatment strategy fails, a complex, multidosed bismuth-based quadruple regimen is recommended. Unfortunately, for patients with heart failure, this salvage regimen can be potentially hazardous due to the drug-drug interaction with tetracycline and digoxin, as well as the large salicylate content with bismuth subsalicylate. As H. pylori infection is so prevalent, providers will most likely encounter such a therapeutic dilemma. A safe, effective, and simplistic alternative is a 10-day fluoroquinolone-based regimen consisting of a proton pump inhibitor, levofloxacin and either clarithromycin or amoxicillin. Levofloxacin demonstrates excellent bioavailability, widespread tissue and fluid distribution, extended half-life, limited drug interaction profile, low incidence of side effects, and remarkable activity against H. pylori with minimal primary resistance. Compared to the 7-day quadruple regimen, a 10-day levofloxacin-based regimen demonstrated a greater eradication rate, better tolerability, and a lower rate of therapy discontinuation. We briefly provide a summary of the data regarding this levofloxacin-based regimen and two successful cases from our heart failure clinic.     

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.     

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.     

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.     

Helicobacter pylori infection: a randomized, controlled study comparing 2 rescue therapies after failure of standard triple therapies

Antibiotic resistance to amoxicillin in second-line eradication therapy for Helicobacter pylori infection is much less frequent than resistance to metronidazole. We conducted a randomized, controlled study to compare the efficacies of standard quadruple rescue therapy and a new therapy with amoxicillin replacing metronidazole for patients failing first-line eradication treatment. We randomly assigned 120 patients who failed H. pylori eradication using a proton pump inhibitor plus clarithromycin and amoxicillin to undergo a 1-week rescue therapy with esomeprazole, bismuth subcitrate, and tetracycline plus either metronidazole (EBTM group, n = 62) or amoxicillin (EBTA group, n = 58). We used follow-up endoscopy 8 weeks after the end of treatment to assess the treatment response. We also examined and analyzed antibiotic resistances and CYP2C19 genotypes. Intention-to-treat analysis demonstrated that the EBTA group had a significantly lower eradication rate than the EBTM group (62% vs. 81%, respectively, p = 0.02). Per-protocol analysis showed similar results (64% vs. 83%, p = 0.01). However, the EBTA group had less frequency of adverse events than the EBTM group (19% vs. 44%, p < 0.01). Both groups had good drug compliance (both 97%). Antibiotic susceptibility tests showed that the frequency of amoxicillin-resistant strains was much less than that of metronidazole-resistant strains (0% vs. 54%, respectively), and there were no significant differences between H. pylori eradication rates and antibiotic resistances. In conclusion, EBTA quadruple therapy demonstrated a lower eradication rate than standard EBTM therapy in second-line rescue treatment. The discrepancy between in vitro antibiotic susceptibility and in vivo eradication response is probably due to drug interactions between combined antibiotics or some unknown causes, and should not be neglected in H. pylori therapy.