Low dose of clarithromycin in triple therapy for the eradication of Helicobacter pylori: One or two weeks?

The aims of this pilot study were: (i) to compare the ef?cacy of low-dose clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate possible therapeutic advantages in associating the low-dose clarithromycin with an anti-secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori infection. We enrolled 129 patients in one of the following schedules: (A) De Nol 120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results were evaluated by Per Protocol (PP) and Intention-To-Treat analysis (ITT). Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5% after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5% in group C; in two cases side effects led to the withdrawal of the treatment. In conclusion, 500 mg clarithromycin per day in association with omeprazole and metronidazole, for 1 week gave comparable results to the same schedule for a 2 week period. The use of clarithromycin with bismuth and metronidazole produced a therapeutic gain compared with both of the anti-secretory schedules, although this was not statistically signi?cant.     

Update on the management of Helicobacter pylori infection, including drug-resistant organisms

Helicobacter pylori infection has many different clinical outcomes. Not all infected persons need to be treated. Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision-making process. Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin is the established treatment of choice. For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin. Bacterial resistance to antibiotics is a major factor adversely affecting treatment success. Resistance to metronidazole has been reported in up to 80%, and resistance to clarithromycin in 2-10% of strains cultured. Resistance to either one of the antibiotics has been reported to result in a drop in efficacy of up to 50%. Emergence of resistance to both metronidazole and clarithromycin following failed therapy is a cause for concern; this underlines the need to use the best available first-line therapy. To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible. For failed treatment, several strategies can be employed. These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs. Quadruple therapy incorporating a bismuth compound with a PPI, tetracycline and metronidazole has been a popular choice as a "rescue" therapy. Ranitidine bismuth citrate has been shown to be able to overcome metronidazole and clarithromycin resistance; it may be a useful compound drug to use in place of a PPI in "rescue" therapies. In the case of persistent treatment failures, it is useful to consider repeating gastroscopy and obtaining tissue for culture, and then prescribe antibiotics according to bacterial susceptibility patterns. It is also important in refractory cases to review the original indication for treatment and determine the importance of the indication.     

Eradication of Helicobacter pylori infection

Eradication of Helicobacter pylori infection has become an important issue recently, because this bacterial species cluster can cause many gastrointestinal diseases. Elevated antibiotic resistance is related to an increasing failure rate of H. pylori eradication. Standard triple therapy is still the first-line therapy; however, according to the Maastricht IV Consensus Report, it should be abandoned in areas of high clarithromycin resistance. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential, concomitant, and hybrid therapies. Quinolone-based triple therapy may be considered as first-line therapy in areas of clarithromycin resistance >15–20% and quinolone resistance <10%. Unique second-line therapy is still unclear, and bismuth-containing quadruple therapy or levofloxacin-based triple therapy can be used as rescue treatment. Third-line therapy should be under culture guidance to select the most effective regimens (such as levofloxacin-based, rifabutin-based, or furazolidone-based therapies). Antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports.     

Helicobacter pylori specific nested PCR assay for the detection of 23S rRNA mutation associated with clarithromycin resistance

Background—Clarithromycin is one ofthe most important antibiotics for Helicobacterpylori eradication. However, 5-10% of strains are reported tobe resistant. It has been shown that one point mutation in the 23S rRNAgene is associated with resistance to clarithromycin.
Aims—To establish a polymerasechain reaction (PCR) system which amplifies a segment of the 23S rRNAgene containing the mutation points with primers specific forH pylori, so that Hpylori infection and the mutation associated with clarithromycinresistance can be examined simultaneously.
Methods—To detectH pylori infection and the mutationsimultaneously, primers specific for the Hpylori 23S rRNA gene were designed based on sequenceconservation among H pylori strains andsequence specificity as compared with other bacteria. DNA from 57 cultured strains and from 39 gastric juice samples was amplified in theseminested 23S rRNA PCR. Clinical applicability was evaluated in 85patients.
Results—DNA samples from 57 cultured strains were all amplified. The novel assay and the urease APCR agreed in 37/39 gastric juice samples with no false positives. Theassay did not amplify the DNA of bacteria other thanH pylori. Eight of 85 samples had themutation before treatment. In clarithromycin based treatment, eradication was achieved in 2/5 (40%) with the mutation and 29/34 (85%) without the mutation.
Conclusion—The assay using gastricjuice is quick (within 12 hours) and non-invasive (endoscopy notrequired), enabling rapid initiation of appropriate antibiotic treatment.

Keywords:Helicobacter pylori; eradication; clarithromycin; resistance; point mutation

     

Efficacy of a 1-week pantoprazole triple therapy in eradicating Helicobacter pylori in Asian patients

BACKGROUND: The aim of the present paper was to determine the efficacy and tolerability of a 1-week treatment regimen consisting of pantoprazole and two antibiotics: clarithromycin and amoxycillin, in the eradication of Helicobacter pylori. METHODS: The patients selected had unequivocal evidence of H. pylori infection based on urease test, culture and histology on antral and corpus biopsies obtained at endoscopy. Patients received pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day and amoxycillin 1 g twice a day for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by culture, histology and urease test. RESULTS: One hundred and six patients were recruited for the study.The mean age was 48.0 years (range: 23-74 years). Four patients defaulted follow up and five patients were not compliant (taking less than 85%) with medications. Eradication rates on per-protocol analysis were: 88/97 (90.7%; 95% CI: 83.1-95.7); and on intention-to-treat analysis they were: 88/106 (83.0%; 95% CI: 75.9-90.2). Side-effects were in general mild and tolerable: 57 of 106 (53.7%) patients complained of a bitter taste; 15 (14.1%) complained of giddiness; 10 (9.4%) complained of increased abdominal pain; 11 (11.5%) complained of lethargy and 16 (15.1%) complained of loose motions. Pre-treatment metronidazole resistance was encountered in 57/74 strains (77.0%). Clarithromycin resistance was not encountered in any of the strains. CONCLUSIONS: The pantoprazole 1-week triple therapy with amoxycillin and clarithromycin is effective in H. pylori eradication. The treatment was well tolerated by patients. Metronidazole resistance was reported in a high percentage of strains isolated from patients. Clarithromycin resistance was, however, not detected in any of the strains.     

Tetracycline, metronidazole and amoxicillin-metronidazole combinations in proton pump inhibitor-based triple therapies are equally effective as alternative therapies against Helicobacter pylori infection

Background: A proton pump inhibitor (PPI)‐based triple therapy with clarithromycin (CAM) and amoxicillin (AMPC) is now a standard regimen for Helicobacter pylori (HP) eradication in Japan. However, the CAM‐resistant rate has increased recently and alternative therapies are sorely needed. Therefore the aim of the present study was to evaluate the effectiveness and safety of the PPI–tetracycline (TC)–metronidazole (MNZ) regimen (the PTM regimen) as an alternative therapy in comparison with the PPI–AMPC–MNZ (PAM) regimen. Methods: Sixty‐four HP‐positive patients visiting the HP‐eradication clinic in Tokai University Hospital from July 1998 to March 2003 were treated with either PTM or PAM as alternative therapies. The HP eradication was assessed by urea breath test (UBT), HP stool antigen test, or HP culture method more than 2 months after completion of the treatments. The drug resistances against CAM, AMPC, TC, and MNZ were assessed by the agar dilution method. Results: Fifty‐six patients (26 PTM and 30 PAM) completed medication and evaluation of the eradication. The eradication rates of PTM were 82.8% (24/29) and 92.3% (24/26), while those of PAM were 74.3% (26/35) and 89.7% (26/29) by intention‐to‐treat and per‐protocol analysis, respectively. The differences between the regimens were not statistically significant. There were no severe adverse effects observed in either of the regimens. The drug‐resistance analyses showed 15 CAM‐ and one MNZ‐resistant cases but no TC or AMPC resistance in the available 25 samples. Conclusion: The PTM and PAM regimens were equally effective and safe as alternative HP eradication therapies. And PTM would be particularly useful in penicillin allergy cases.     

Comparison of the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of Helicobacter pylori infection

BACKGROUND: The proton pump inhibitor (PPI)‐based 7‐day triple therapy is the regimen with the highest cure rates for eradication of Helicobacter pylori infection and has been recommended as the first‐line regimen in the world. It had been reported that a 1‐day quadruple therapy could also successfully cure 95% of the H. pylori infected patients. OBJECTIVES: To observe the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of H. pylori infection, and to observe side‐effects of the two different regimens. METHODS: This randomized, open, parallel‐controlled study was conducted at Renji Hospital between November 2004 to March 2005. A total of 80 consecutive patients with non‐ulcer dyspepsia, who were H. pylori positive proven by both rapid urease test and histology were included and randomly assigned to 1‐day quadruple therapy or 7‐day triple therapy. Thirty‐nine patients were administered with 1‐day high‐dose quadruple therapy including esomeprazole 40 mg b.i.d., colloidal bismuth subcitrate 440 mg q.i.d., amoxicillin 2 g q.i.d. and metronidazole (400 mg q.i.d.) for 1 day. Forty‐one patients received a standard 7‐day triple therapy consisting of esomeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. for 7 days. The eradication rates were evaluated by the ¹³C‐urea breath test at least 4 weeks after completion of a course treatment. RESULTS: Seventy‐seven patients completed the trial and three patients dropped out. The eradication rates in the 1‐day therapeutic group and the 7‐day therapeutic group were 39.5% (15/38) and 84.6% (33/39), respectively. There was a statistically significant difference between the two groups (P < 0.0001). Short‐lasting and self‐limiting side effects including thirst, a metallic taste, diarrhea and abdominal pain were reported in three patients (7.9%) in the 1‐day group and seven patients (18%) in the 7‐day group (P = 0.31). CONCLUSIONS: A 1‐day high‐dose quadruple therapy with amoxicillin, metronidazole, bismuth salt, and esomeprazole is not effective for eradication of H. pylori compared with the standard 7‐day triple therapy.     

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 efficacy of triple versus quadruple therapy on the eradication of Helicobacter pylori and antibiotic resistance

OBJECTIVE: Our aim was to compare the efficacy and safety of Helicobacter pylori (H. pylori) eradication with pantoprazole-based 7-day standard triple therapy (PAC) and 10-day quadruple therapy (PBMT), and to study the primary resistance of H. pylori to amoxicillin, clarithromycin, metronidazole and tetracycline. METHODS: A total of 170 patients with non-ulcer dyspepsia (NUD) and H. pylori infection were allocated to two study groups. The PAC group received pantoprazole 40 mg b.i.d., amoxicillin 1.0 g b.i.d. and clarithromycin 500 mg b.i.d. for 7 days; the PBMT group received pantoprazole 40 mg b.i.d., colloidal bismuth subcitrate 220 mg b.i.d, metronidazole 400 mg t.i.d. and tetracycline 750 mg b.i.d. for 10 days. A total of 80 H. pylori strains were isolated and antibiotic resistance was measured by the agar dilution method. RESULTS: A total of 166 patients completed the therapy. The intention-to-treat eradication rates in the PAC and PBMT groups were 63.5% and 89.4%, respectively (P < 0.05). By per protocol analysis, the eradication rates of the two groups were 65.1% and 91.6%, respectively (P < 0.05). Overall 77 clinical isolated H. pylori strains were cultured successfully. The H. pylori primary resistance rates to metronidazole and clarithromycin were 41.6% and 20.8%, respectively, whereas all the H. pylori isolates were sensitive to amoxicillin and tetracycline. CONCLUSION: The efficacy of PAC declines in many regions in China because of high antibiotic resistance rates. The PBMT regimen achieved a high eradication rate of H. pylori and might be used as a first-line therapy.     

Prevalence of primary Helicobacter pylori resistance to metronidazole and clarithromycin in Singapore

INTRODUCTION Eradication of Helicobacter pylori, a bacterium residing in stomach and causing peptic ulcer disease,can be achieved by using combination therapies consisting of one or two antibiotics with a proton pump inhibitor (PPI). The major antibiotics widely used in the regimens to eradicate H. Pylori are metronidazole and clarithromycin[1-3].     

A randomized controlled trial to compare Helicobacter pylori eradication rates between the empirical concomitant therapy and tailored therapy based on 23S rRNA point mutations

Background:Increasing clarithromycin resistance has led to changes in several guidelines for treatment of Helicobacter pylori infections. We compared the H. pylori eradication rates of the empirical concomitant therapy (CoT) and a tailored therapy (TaT) using dual-priming oligonucleotide-based polymerase chain reaction to detect mutations in the 23S rRNA gene that are related to clarithromycin resistance.Methods:Between June 2020 and May 2021, 290 patients were enrolled and randomly assigned to 2 groups. In the CoT group, the patients received rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 14 days. In the TaT group, point mutation-negative patients received rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days and point mutation-positive patients received rabeprazole 20 mg twice daily, metronidazole 500 mg thrice daily, and bismuth 120 mg and tetracycline 500 mg 4 times daily for 14 days.Results:A total of 290 and 261 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. A2142G and/or A2143G point mutations were identified in 28.6% of the patients. No significant difference in eradication rates were observed between the 2 groups as per ITT (CoT, 82.8% and TaT, 85.5%, P = .520) and PP (CoT, 88.6% and TaT, 94.6%, P = .084) analyses. In point mutation-positive patients, the eradication rates in the CoT group were lower than those in the TaT group as per ITT (69.8% and 87.5%, respectively, P = .050) and PP (76.9% and 97.1%, respectively, P = .011) analyses.Conclusion:CoT and TaT showed similar overall eradication rates for H. pylori. However, CoT eradication rate was suboptimal, especially in point mutation-positive patients.     

枯草杆菌二联活菌联合四联疗法根除幽门螺杆菌临床疗效观察

[目的]观察枯草杆菌二联活菌联合四联疗法对幽门螺杆菌(Hp)的根治效果。[方法]105例诊断为慢性糜烂性胃炎伴有Hp感染的患者随机分为A组(35例)、B组(36例)、C组(34例)。A组用三联疗法(泮托拉唑40mg,bid+阿莫西林1 000mg,bid+克拉霉素500mg,bid),B组用四联疗法(果胶铋+三联疗法),C组用枯草杆菌二联活菌0.5,tid+四联疗法,各组疗程均为14d。疗程结束后至少间隔4周行13 C尿素呼气实验评估治疗结果。记录治疗期间和治疗后不良反应发生情况。[结果]A组、B组、C组患者Hp根除率按意图治疗(ITT)分析分别为62.9%、86.1%、91.2%,按方案(PP)分析分别为68.8%、88.6%和93.9%。B组、C组的疗效明显优于A组(P0.05);A组、B组、C组的不良反应发生率分别为18.7%、20.0%、3.0%。C组的不良反应发生率明显低于A组、B组(P0.05)。[结论]四联疗法对Hp根除率高于三联疗法;四联疗法加枯草杆菌二联活菌尽管不能显著提升Hp根除率,但能有效的减少治疗过程中的不良反应发生率。     

A new quadruple therapy for the eradication of Helicobacter pylori. Effect of pretreatment with omeprazole on the cure rate

To elucidate whether pretreatment with omeprazole decreases the cure rate of Helicobacter pylori infection with a new quadruple therapy, and thus, whether this pretreatment should not be used in clinical practice, we conducted a randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for 2 weeks (days 1–14), and 500 mg amoxicillin granules and 250 mg metronidazole thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8–14), Group 2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1–7), in addition to omeprazole treatment for 2 weeks (days 1–14). Four weeks after the treatment ended, endoscopy was repeated, with two biopsy specimens each taken from the antrum and the corpus (total of four specimens) for a urease test, histological analysis, and culture to establish cure of infection. A patient was regarded as cured only if all three methods gave negative results for H. pylori. In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence intervals [CI], 81.7%–98.6%) in group 1 were cured compared with 43 of 45 patients (95.6%; 95% CI, 84.9%–99.5%) in group 2. In the per-protocol analysis, the corresponding figures were 42/44 (95.5%; 95% CI 84.5%–99.4%) and 43/44 (97.7%; 95% CI, 88.0%–99.9%). There were no significant differences in the cure rate between the two groups on either analysis. All patients, except for one who had an allergic reaction, completed the treatment regimens. Fifty to sixty percent of the patients had no side effects while the rest had mild to moderate side effects. The new quadruple therapy consisting of omeprazole, amoxicillin, metronidazole, and roxithromycin appears suitable for use in clinical practice, as the cure rate was 95% and no severe side effects were observed. Pretreatment with omeprazole did not reduce the cure rate for this new quadruple therapy. (Received Sept. 29, 1997; accepted Jan. 23, 1998)     

舒肝解郁胶囊联合四联疗法治疗幽门螺杆菌阳性胃溃疡临床观察

[目的]观察舒肝解郁胶囊联合四联疗法(埃索美拉唑、阿莫西林、胶体果胶铋、克拉霉素)对幽门螺杆菌(Hp)阳性胃溃疡的临床疗效与安全性。[方法]89例Hp阳性胃溃疡患者,随机分为观察组(45例)、对照组(44例)。对照组采用四联疗法治疗2周,然后予以埃索美拉唑抑酸治疗4周;观察组在对照组基础上从第1~6周加用舒肝解郁胶囊2片、2次/d进行治疗。观察2组患者胃泌素浓度(GAS)、胃动素浓度(MTL)、临床症状评分、疗效、Hp根除率及用药不良反应。[结果]经过6周治疗,2组患者GAS浓度、MTL浓度及临床症状评分较治疗前均有显著改善;观察组患者GAS浓度、MTL浓度及临床症状评分均显著低于对照组(P<0.05);观察组治疗总有效率为95.56%、Hp根除率为93.33%,显著高于对照组(P<0.05);观察组不良反应发生率显著低于对照组(P<0.05)。[结论]舒肝解郁胶囊联合四联疗法治疗Hp阳性溃疡相对于四联疗法可更有效缓解患者临床症状、提高溃疡愈合率和Hp根除率,不良反应相对较少,值得推广。     

The efficacy of bismuth containing quadruple therapy as a first-line treatment option for Helicobacter pylori

BACKGROUND: Helicobacter pylori eradication rates have tended to decrease recently, mostly due to increasing antibiotic-resistance. The present study aimed to compare the efficacy of bismuth-based quadruple regimen with proton pump inhibitor-based triple regimen for eradication of H. pylori. METHODS: Consecutive H. pylori-positive patients with non-ulcer dyspepsia were randomized into one of two regimens: (i) bismuth subsalicylate 300 mg q.i.d., lansoprazole 30 mg b.i.d., tetracycline 500 mg q.i.d. and metronidazole 500 mg t.i.d. (BLTM group) for 14 days; (ii) lansoprazole 30 mg b.i.d., amoxicillin 1 g b.i.d and clarithromycin 500 mg b.i.d. (LAC) for 14 days. Gastroscopy and (14)C-Urea breath test (UBT) were performed before enrollment, and UBT only was repeated for 6 weeks after treatment. RESULTS: A total of 240 patients were randomized into groups and 212 of them completed the protocols. The 'intention-to-treat' (ITT) and 'per protocol' (PP) H. pylori eradication rates were 70% (95%CI 61-78) and 82.3% (95%CI 74-89) in the BLTM group, and 57.5% (95%CI 48-66) and 62.7% (95%CI 53-71) in the LAC group. The BLTM treatment achieved a significantly better eradication rate compared with LAC treatment in PP analysis (82.3% vs. 62.7%, P = 0.002). Mild to severe side-effects, which were more frequent in the BLTM group, were reported in 18.2% of the patients. CONCLUSION: The bismuth-based quadruple regimen achieved a better eradication rate compared with proton pump inhibitor-based triple regimens as a first-line eradication option for H. pylori in our population.     

Ranitidine bismuth citrate-based triple therapies as a second-line therapy for Helicobacter pylori in Turkish patients

BACKGROUND: Quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as the optimal second-line therapy of Helicobacter pylori infection in the Maastricht Consensus Report. The aim of the present paper was to evaluate the efficacy of ranitidine bismuth citrate (RBC)-based regimens as second-line therapies after failure of the standard Maastricht triple therapy. MATERIALS AND METHODS: One hundred and sixteen H. pylori-positive patients were given omeprazole 20 mg b.d., clarithromycin 500 mg b.d., and amoxicillin 1 g b.d for 10 days. Patients remaining H. pylori-positive (n = 29) were combined with 27 patients enrolled after an initial eradication failure from proton-pump inhibitor (PPI), amoxicillin and clarithromycin therapy for at least 7 days and were randomly given one of the following second-line 10-day treatments: RBC 400 mg b.d., amoxicillin 1 g b.d and clarithromycin 500 mg b.d. (RAC group, n = 28) and RBC 400 mg b.d., metronidazole 500 mg b.d and tetracycline 500 mg b.d. (RMT group, n = 28). Eradication was assessed by either histology and rapid urease test or (13)C urea breath test 8 weeks after therapy. RESULTS: The eradication rate of first-line Maastricht therapy was 67% for intention-to-treat analysis (95% confidence interval [CI]: 58-75). Per-protocol and intention-to-treat eradication was achieved in 60.7% of patients (95%CI: 42-79) in the RAC group and in 85.7% of patients (95%CI: 73-98) in the RMT group (P = 0.03). Fifty-three percent of patients in the RAC and 50% of patients in the RMT group experienced at least one slight side-effect (P = 0.6). CONCLUSIONS: RMT is an effective and well-tolerated second-line therapy after H. pylori eradication failure from PPI, amoxicillin, and clarithromycin.     

Helicobacter pylori treatment and antibiotic susceptibility: results of a five-year audit

Background: Helicobacter pylori eradication treatment has been a rapidly evolving field. Audit of treatment results provides reassurance that trial data can be translated into routine clinical practice. Methods: Data were collected prospectively over five years. Patients were given four different treatment regimens over the audit period ‘standard’ triple therapy, two types of clarithromycin-based treatment or ranitidine, amoxycillin and metronidazole. Eradication was proven by a urea breath test at least four weeks after completing treatment. Results: Eradication treatment for H. pylori was given to 665 patients; 89% had follow-up data. H. pylori eradication was significantly associated with treatment type (p<0.0001) and smoking (p=0.04) by univariate analysis, but was not associated with sex, age, alcohol consumption, endoscopic diagnosis, recent treatment with anti-secretory drugs or NSAIDs. By logistic regression analysis, only treatment type was significant (p=0.0001). H. pylori culture and sensitivities were available for 255 patients. Metronidazole resistance was shown for 84 isolates (32%) and clarithromycin resistance for 18 isolates (6.8%). Metronidazole resistance was significantly associated with younger age (p=0.02), ethnicity (p=0.02), female sex (p=0.02), and year of endoscopy (p=0.04), but was not associated with clarithromycin resistance. Clarithromycin resistance was not associated with age, sex, or ethnicity. Metronidazole resistance significantly affected H. pylori eradication for regimens containing metronidazole without clarithromycin. Eradication with metronidazole without clarithromycin was achieved in 90% of sensitive strains but only 55% of resistant strains (p<0.001). Metronidazole resistance was not significantly associated with treatment failure when metronidazole was combined with clarithromycin. Eradication with metronidazole and clarithromycin was achieved in 86% of sensitive strains and 78% of resistant strains (p=0.42). Conclusion: Treatment type and antibiotic susceptibility are the most important determinants of treatment success.     

Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxaci...     

Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance

Background and Aim: New regimens, including those with new fluoroquinolones, have been developed to overcome the antibiotic resistance of Helicobacter pylori. We aimed to assess the antibiotic resistance rates, as well as the molecular mechanisms of fluoroquinolone resistance, of the clinical isolates obtained in Korea. Methods: The minimal inhibitory concentration (MIC) values of ciprofloxacin, amoxicillin, clarithromycin, metronidazole and tetracycline were determined by the agar dilution method for 185 treatment‐naïve Helicobacter pylori isolates. The resistant strains were evaluated for the presence of point mutations in the quinolone resistance‐determining region (QRDR) of the gyrA and gyrB genes by direct nucleotide sequencing. Results: Twenty‐nine (29/185, 15.7%) of the strains were found to be resistant to ciprofloxacin. The resistance rates to amoxicillin, clarithromycin, metronidazole and tetracycline were 2.2% (four of 185), 10.8% (20 of 185), 30.3% (56 of 185) and 0.5% (one of 185), respectively. The most common mutations in the H. pylori gyrA gene were found at codons corresponding to Asp87 (16/29, 55.2%) and Asn91 (10/29, 34.5%). Conclusions: Primary H. pylori resistance to ciprofloxacin occurred at a high frequency. The fluoroquinolone resistance is most likely mediated through amino acid point mutation in the gyrA gene at Asn87 and Asp91.