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.     

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.     

Effects of in vitro antibiotic resistance on treatment: bismuth-containing regimens.

Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and, most recently, ranitidine bismuth citrate (RBC). CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A) only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.     

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。     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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。     

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.     

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.     

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.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

Helicobacter pylori diagnosis and management

H pylori is a global human pathogen and is the major cause of gastritis and the gastritis-associated diseases: gastric ulcer, duodenal ulcer, gastric cancer, and primary gastric B-cell lymphoma (MALToma). Although several reliable diagnostic tests are widely available, the ideal regimen for treating the infection re-mains to be established. The current first-line or legacy triple therapy regimens fail in 20% to 40% of patients. Causes of treatment failure include antibiotic resistance, poor compliance, short (7-10 days) duration of therapy, and drug-related side effects. Fourteen-day triple therapy has an approximately 12% better cure rate than does 7-day therapy; therefore, shorter durations can no longer be recommended. Recent studies confirmed older observations that the success rate of legacy triple regimens (PPI plus two antibiotics) can be improved if the duration is extended to 14 days or if a third antibiotic is given. Sequential therapy (PPI plus amoxicillin followed by a PPI plus clarithromycin plus metronidazole) requires further evaluation although the concept appears very promising and therapy should probably replace the legacy triple therapies. More studies are needed to examine doses, durations, and the need for sequential administration of the drugs, which extends the duration to 14 days. Nonetheless, sequential quadruple therapy probably should replace the legacy triple therapies. Classic quadruple therapy contains bismuth, a PPI, 1500 mg of metronidazole, and 1500 mg of tetracycline. It provides the highest average eradication rates and in many regions should be considered as the initial approach. Confirmation of eradication using noninvasive diagnostic tests, such as a urea breath test or stool antigen assay, is now the standard of care. The diagnosis of latent or symptomatic H pylori like the diagnosis of latent or symptomatic syphilis, always should prompt treatment. Because of decreasing cure rates, new and improved therapies are needed.     

Efficacy of levofloxacin-based triple therapy as second-line Helicobacter pylori eradication]

BACKGROUND/AIMS: Bismuth-based quadruple therapy for second-line eradication treatment achieves the eradication rate ranging from 70% to 81% due to antimicrobial resistance and poor compliance. The aim of this study was to compare the eradication rate of levofloxacin-based triple therapy with that of bismuth-based quadruple therapy in second-line Helicobacter pylori (H. pylori) eradication therapy. METHODS: Seventy-six outpatients with persistent H. pylori infection after first-line triple therapy were enrolled in this prospective randomized trial. The subjects were randomized to receive levofloxacin 300 mg, amoxicillin 1 g, and pantoprazole 20 mg, given twice daily for 7 days (LAP group), or metronidazole 500 mg twice, tetracycline 500 mg four times, and pantoprazole 20 mg twice, bismuth subcitrate 600 mg twice daily for 7 days (MTPB group). Eradication was confirmed with (13)C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. RESULTS: Among Seventy-six patients initially included, eleven were lost during follow-up. The eradication rates, expressed as intention to treat (ITT) and per protocol (PP) analyses, were 51.6% and 53.3% in the LAP group, and 48.9% and 62.9% in the MTPB group, respectively. There was no significant difference in H. pylori eradication rates between the two groups (p=0.815 by ITT, p=0.437 by PP). LAP regimen was better tolerated than MTPB regimen with lower incidence of side effects (10.0% versus 31.4%, p=0.03). CONCLUSIONS: H. pylori eradication rates of levofloxacin-based triple therapy and bismuth-based quadruple therapy were not significantly different in second-line H. pylori eradication therapy, and low incidence of side effects was observed in levofloxacin-based triple therapy.     

Optimal therapy for Helicobacter pylori infections

Although Helicobacter pylori infection is both a common and a serious bacterial infection, antimicrobial therapies have rarely been optimized, are prescribed empirically, and provide inferior results compared with antimicrobial therapies for other common infectious diseases. The effectiveness of many of the frequently recommended H. pylori infection treatment regimens has been increasingly compromised by antimicrobial resistance. Regional data on the susceptibility of strains of H. pylori to available antimicrobials are sorely needed. Noninvasive molecular methods are possible to assess clarithromycin susceptibility in isolates obtained from stool specimens. As a general rule, clinicians should prescribe therapeutic regimens that have a ≥90% or, preferably, ≥95% eradication rate locally. If no available regimen can achieve a ≥90% eradication rate, clinicians should use the most effective regimen(s) available locally. Eradication of infection should always be confirmed after treatment in order to provide feedback regarding local effectiveness and an early warning of increasing resistance. In most regions of the world, four-drug treatment regimens, including a PPI plus three antimicrobials (clarithromycin, metronidazole/tinidazole and amoxicillin), or a PPI plus a bismuth plus tetracycline and metronidazole provide the best results. Standard triple therapy (a PPI, amoxicillin and clarithromycin) should now be avoided owing to increasing resistance to this treatment.