'Rescue' therapy with rifabutin after multiple Helicobacter pylori treatment failures

Aim. Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A ‘rescue’ therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin‐based regimen in patients with two consecutive H. pylori eradication failures. Patients and Methods. Design: Prospective multicenter study. Patients: Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. Intervention: A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Outcome: H. pylori eradication was defined as a negative ¹³C‐urea breath test 8 weeks after completing therapy. Results. Fourteen patients have been included. Mean age ± SD was 42 ± 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per‐protocol and intention‐to‐treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49–95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. Conclusion. Rifabutin‐based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline.     

Nonbismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and versus sequential therapy for clarithromycin-resistant strains

Background:  Using quadruple clarithromycin‐containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. Aim:  To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. Methods:  209 consecutive naive H. pylori‐positive patients without susceptibility testing were empirically treated with 10‐day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin‐susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin‐resistant strains. Eradication was confirmed with ¹³C‐urea breath test or histology 8 weeks after completion of treatment. Results:  Per‐protocol (PP) and intention‐to‐treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84–93%) and 87% (83–92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin‐susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82–100%) vs 74% (58–91%), p = 0.05] and by intention to treat [92% (82–100%) vs 70% (57–90%), p = 0.02]. As for antibiotic‐resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin‐resistant/metronidazole‐susceptible strains and 75% (3/4) vs 60% (3/5) for dual‐resistant strains. Conclusions:  Empirical 10‐day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin‐susceptible H. pylori and at least as effective as sequential therapy for resistant strains.     

Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days

Background: Ten‐day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90–94% (Grade B success). Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14‐day treatment period would produce a ≥95% result. Methods: This was a multicenter pilot study in which H. pylori‐infected patients received a 14‐day sequential–concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥95% eradication by per‐protocol analysis. Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3–100.0%) by per‐protocol analysis and 97.4% by intention‐to‐treat analysis (95% CI, 94.5–100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%. Conclusions: Fourteen‐day hybrid sequential–concomitant therapy achieved >95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.     

Ten‐Day Sequential Therapy as First‐line Treatment for Helicobacter pylori Infection in Korea: A Retrospective Study

Background and Aims: The eradication rate of proton‐pump inhibitor‐based triple therapy for Helicobacter pylori infection is low due to increasing antibiotics resistance, especially clarithromycin. Recently, it was reported in Europe that a 10‐day sequential strategy produced good outcomes. The aim of this study was to assess the efficacy of sequential therapy as first‐line treatment for eradication of H. pylori in clinical practice in Korea. Materials and Methods: A total of 98 patients (mean age 55.2 years and male 47, female 51) with proven H. pylori infection received 10‐day sequential therapy (20 mg of rabeprazole, and 1 g of amoxicillin, twice daily for the first 5 days, followed by 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for the remaining 5 days). Eradication was evaluated 4 weeks later, after completion of treatment by 13^C‐urea breath testing. Eradication rates were calculated by intention‐to‐treat (ITT) and by per protocol (PP). Compliance and adverse events were also assessed in study group. Results: The eradication rate of sequential therapy was 91.8% (90/98) by ITT and same result was reported by PP analysis (89/97). The study group consisted of 66 H. pylori associated gastritis, 7 gastric ulcer, and 25 duodenal ulcer patients (67.3%, 7.1%, 25.5%, respectively). Mild adverse events happened frequently (21.4%) but the treatment was well tolerable. The most common adverse event was a bitter taste (9.2%) followed by nausea and diarrhea (4.1%). Conclusions: Ten‐day sequential therapy is found to effectively eradicate H. pylori infection as first‐line treatment in Korea.     

Comparison of lafutidine and rabeprazole in 7-day second-line amoxicillin- and metronidazole-containing triple therapy for Helicobacter pylori: a pilot study

Background: Lafutidine is an H2‐receptor antagonist with gastroprotective action through capsaicin‐sensitive afferent neurons and relatively inexpensive compare to proton‐pump inhibitors (PPIs). A 7‐day course of PPIs–amoxicillin–metronidazole is recommended as standard second‐line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second‐line eradication using the H2‐receptor antagonist lafutidine as a substitute for a PPI. Materials and Methods: Fifty‐two patients who failed in first‐line eradication using PPI–amoxicillin–clarithromycin were randomly assigned to a 7‐day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ‐AM) or a 7‐day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT‐AM) as second‐line therapy. Eradication was assessed by the ¹³C urea breath test. A drug susceptibility test was performed before the second‐line therapy. Results: Prior to second‐line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT‐AM and RPZ‐AM groups were 96% (95%CI = 88.6–100%). There were no severe adverse events in either group. Conclusions: Lafutidine plus metronidazole–amoxicillin as second‐line therapy provided a high eradication rate and safe treatment similar to a PPI‐based regimen. Lafutidine‐based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.     

Review: Clinical Management of Helicobacter pylori Infection in China

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.     

Quadruple therapy with medications containing either rufloxacin or furazolidone as a rescue regimen in the treatment of Helicobacter pylori-infected dyspepsia patients: a randomized pilot study

Background: The eradication rates of first‐line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. Aims: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. Methods: One hundred and thirty‐eight patients after an unsuccessful 10‐day standard triple therapy were enrolled in this study. They were randomized to receive a 14‐day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n = 70) or levofloxacin (Group Lev, n = 68). The H. pylori eradication was evaluated by ¹³C‐urea breath test 4 and 12 weeks after therapy was completed. Results: One hundred and twenty‐seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention‐to‐treat (ITT) analysis and 87.7% for per‐protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p < 0.05). There were no severe adverse effects found in these two groups. Conclusions: Fourteen‐day quadruple therapy with a combination of proton‐pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

A Randomized Controlled Trial: Efficacy and Safety of Azithromycin,Ofloxacin, Bismuth,and Omeprazole Compared With Amoxicillin,Clarithromycin, Bismuth,and Omeprazole as Second‐Line Therapy in Patients With Helicobacter pylori Infection

Background: Helicobacter pylori infection of the stomach is widespread among human populations and is considered to play a major role in the pathogenesis of various diseases such as peptic ulcer, adenocarcinoma, and mucosa associated lymphoid tissue (MALT) lymphoma of the stomach. To increase H. pylori eradication rate without increasing bacterial resistance, various regimens have been recommended. Commonly the association of at least two antibiotics with a proton‐pump inhibitor is used. The treatment regimens for second‐line therapy, suggested in studies from the western world may not be ideal in Iran. Aim: In this study, we evaluated the safety and efficacy of a new quadruple therapy regimen and compared it with the standard second‐line treatment for H. pylori eradication. Methods: We selected 220 H. pylori positive patients, with a clear indication of eradication therapy, who did not respond to a 2 weeks treatment with metronidazole, amoxicillin, omeprazole, and bismuth. They were randomized into two groups. Group A (n = 110) were treated with azithromycin, ofloxacin, bismuth, and omeprazole and group B (n = 110) with amoxicillin, clarithromycin, bismuth, and omeprazole for 2 weeks. Four weeks after the end of treatment, urea breath test was performed for all subjects to confirm eradication. Results: In intention‐to‐treat analysis, the rate of H. pylori eradication in groups A and B was 77.3% (85/110) and 64.5% (71/110) respectively (p = .027). In per‐protocol analysis, the rate of H. pylori eradication in groups A and B was 86.7 and 74.7%, respectively (p = .026). The incidence of poor compliance was lower, although not significantly so, in group A than group B (3.5 vs 4.3%). No major adverse events occurred in both groups. Conclusion: Two weeks of treatment with ofloxacin, azithromycin, omeprazole, and bismuth is an effective and safe regimen for H. pylori eradication as second‐line therapy.     

A prospective,randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin

Background and Aim. Failure of primary anti‐H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high‐dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin. Patients and Methods. Patients with at least one treatment failure and infected with H. pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 × 40 mg and amoxicillin 4 × 750 mg; or omeprazole 2 × 20 mg, bismuthcitrate 4 × 107 mg, metronidazole 4 × 500 mg and tetracycline 4 × 500 mg. Both regimens were given for 14 days. In cases of persistent infection, a cross‐over therapy was performed. Results. Eighty‐four patients were randomized. Cure of H. pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9–93.8) and 92.1% (95% CI, 78.6–98.3), respectively (p = 0.71); intention to treat: 75.6% (95% CI: 59.7–87.6) and 81.4% (95% CI: 66.6–91.6), respectively (p = 0.60)). Cross‐over therapy was performed in six of nine patients, four of whom were cured of the infection. Conclusion. Both high‐dose dual therapy and quadruple therapy are effective in curing H. pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures.     

Is There a Benefit to Extending the Duration of Helicobacter pylori Sequential Therapy to 14 Days?

Background and Aims: Ten‐day sequential therapy with a proton‐pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori (H. pylori) eradication rates between 90 and 94% (i.e., Grade B success). It has been suggested that prolonging the duration of therapy might improve the treatment success. We tested whether prolonging treatment duration to 14‐days would improve the results to 95% or greater eradication. Methods: This was a multi‐center, single site, pilot study in which H. pylori‐infected patients received a 14‐day sequential therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, clarithromycin, and metronidazole for 7 days). H. pylori status was assessed 8 weeks after therapy. Success was defined as achieving 95% or greater eradication by per‐protocol (PP) analysis. Results: One hundred and twenty‐three subjects received the 14‐day sequential therapy. The eradication rate was 93.9% (95% confidence interval [CI], 89.5–98.3%) by PP and 91.9% (95% CI, 87.1–96.7%) by intention‐to‐treat analysis. Adverse events were experienced by 21.1%; compliance of 90% or greater was 95.9%. Conclusions: Extending sequential therapy to 14 days did not result in improving the treatment outcome to 95% or greater.     

Eradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies

Aim. To compare the short‐term (7‐day) safety and efficacy of two triple‐therapy regimens using pantoprazole with those of two dual‐therapy regimens (one with pantoprazole and one without), for Helicobacter pylori eradication in patients with peptic ulcer disease. Methods. H. pylori infection was identified by rapid urease (CLOtest), and confirmed by histology and culture. Patients were enrolled into one of two randomized, double‐blind, multicenter, parallel‐group studies. In study A, patients received oral pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg (PCM); pantoprazole, clarithromycin and amoxicillin 1000 mg (PCA); or pantoprazole and clarithromycin (PC). In study B, patients received PCM, PCA, PC, or clarithromycin and metronidazole without pantoprazole (CM). Treatments were given twice daily for 7 days. H. pylori status after therapy was assessed by histology and culture at 4 weeks after completing the course of study treatment. Modified intent‐to‐treat (MITT; each study: n = 424, n = 512) and per‐protocol (PP; each study: n = 371, n = 454) populations were analyzed. The MITT population comprised all patients whose positive H. pylori status was confirmed by culture and histology; the PP population comprised patients who also complied with ≥ 85% of study medication doses. Results. A total of 1016 patients were enrolled. Cure rates among patients with clarithromycin‐susceptible H. pylori strains were 82 and 86% for PCM, and 72 and 71% for PCA, in studies A and B, respectively. Cure rates among patients with metronidazole‐susceptible H. pylori strains were 82 and 87% for PCM, and 71 and 69% for PCA, in studies A and B, respectively. The combined eradication rates observed with the PCM regimen were superior to those of all other regimens tested. Side‐effects were infrequent and mild. Conclusions. PCM had the highest overall eradication rate in these two studies examining 7‐day treatment regimens. All regimens were safe and well tolerated.     

A Randomized Clinical Trial to Determine the Efficacy of Regimens Containing Clarithromycin, Metronidazole, and Amoxicillin Among Histologic Subgroups for Helicobacter pylori Eradication in a Developing Country

Background: Most treatments deemed effective for Helicobacter pylori eradication in developed countries are less effective in developing countries. Regimens containing clarithromycin, metronidazole, and amoxicillin seem efficacious despite antibiotic resistance, and may be a viable option in developing countries. Materials and Methods: We evaluated the efficacy of a 14‐day regimen with 500 mg clarithromycin b.i.d., 500 mg metronidazole t.i.d., and 500 mg amoxicillin t.i.d. (with and without a proton pump inhibitor), and a 10‐day regimen containing 500 mg clarithromycin b.i.d., 1 g amoxicillin b.i.d., and 20 mg omeprazole b.i.d. in Pasto, Colombia, using a randomized, single‐blind design stratified by presence of atrophic gastritis. Results: H. pylori was eradicated in 86.8% and 85.3% of the participants randomized to a clarithromycin‐metronidazole‐amoxicillin and clarithromycin‐amoxicillin‐omeprazole regimens, respectively (p = .79). Per‐protocol analyses indicated greater efficacy for the clarithromycin‐metronidazole‐amoxicillin regimen (97%) versus the clarithromycin‐amoxicillin‐omeprazole regimen (86%) (p = .04), particularly for participants with atrophic gastritis (clarithromycin‐metronidazole‐amoxicillin = 100%, clarithromycin‐amoxicillin‐omeprazole = 81%; p = .02). Adverse events were mild, but adverse event‐related non‐compliance was reported more often for regimens containing clarithromycin, metronidazole, and amoxicillin. Conclusions: Our results suggest that an eradication rate of > 85% can be achieved with 14‐day clarithromycin, metronidazole, and amoxicillin and 10‐day clarithromycin, amoxicillin, and omeprazole regimens in Pasto, Colombia. The regimens containing clarithromycin, metronidazole, and amoxicillin appear to be superior to the clarithromycin, amoxicillin, and omeprazole regimen for compliant participants and those with atrophic gastritis. Our findings provide treatment options for a population in a developing country with a high prevalence of H. pylori infections and antibiotic resistance.     

Colloidal Bismuth Pectin: An Alternative to Bismuth Subcitrate for the Treatment of Helicobacter pylori– Positive Duodenal Ulcer

Background. Bismuth triple therapy provides consistently good results in Helicobacter pylori eradication worldwide, whereas quadruple therapy using a combination of omeprazole and bismuth triple regimen has produced cure rates in excess of 90%. The prevalence of metronidazole-resistant strains was 26.8% in our area. Colloidal bismuth pectin (CBP) is a new, lower-priced bismuth salt made in China. The purpose of this study was to investigate the efficacy and safety of CBP triple and quadruple regimens in the treatment of H. pylori–positive duodenal ulcer. Materials and Methods. In this prospective trial, 205 patients with H. pylori–positive duodenal ulcer were allocated randomly to receive one of four regimens: metronidazole, 200 mg; amoxicillin, 250 mg; and colloidal bismuth subcitrate (CBS), 120 mg (group 1), or CBP, 100 mg qid (group 2) for 2 weeks, then continued CBS, 240 mg, or CBP, 200 mg bid for a further 2 weeks. A quadruple regimen using a combination of omeprazole, 20 mg bid, and CBS triple therapy (group 3) or CBP triple therapy (group 4), respectively, was given to patients for 1 week, followed by omeprazole, 20 mg once daily for a further 3 weeks. Further endoscopy was performed at least 4 weeks after cessation of the treatment. H. pylori status was determined by histology, a ¹⁴C urea breath test, and a urease test. Results. The per-protocol H. pylori cure rates were 85% (22 of 26 patients), 90% (35 of 39), 96% (46 of 48), and 95% (75 of 79) for groups 1 through 4. In the intention-to-treat analysis, cure rates were 79% (22 of 28), 83% (35 of 42), 90% (46 of 51), and 89% (75 of 84), respectively. The cure rates of quadruple therapy were higher than those of triple therapy; an 8.2% difference was not statistically significant (95% confidence interval [CI], 2.3–18.7%). The ulcer-healing rates were 88%, 87%, 98%, and 97%, respectively, for groups 1 through 4. The ulcer pain was relieved more rapidly in quadruple- than in triple-therapy regimens. Two patients discontinued treatment prematurely owing to drug-related side effects. Conclusion. One-week quadruple therapy is highly effective and safe in H. pylori eradication in Chinese patients. CBP is as effective as CBS.     

Clarithromycin–Amoxycillin‐Containing Triple Therapy: A Valid Empirical First‐Line Treatment for Helicobacter pylori Eradication in Hong Kong?

Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin–clarithromycin‐containing triple therapy as first‐line treatment have fallen below 80%. Levofloxacin‐containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7‐day clarithromycin‐containing triple therapy against the 7‐day levofloxacin‐containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first‐line treatment for H. pylori infection in Hong Kong. Methods: Three hundred consecutive H. pylori‐positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by ¹³C‐urea breath test 6 weeks after treatment. Patients who failed either of the first‐line eradication therapy were invited to undergo H. pylori susceptibility testing. Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention‐to‐treat and per‐protocol analysis. More patients in the clarithromycin‐ than the levofloxacin‐containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 μg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 μg/mL). Conclusions: The standard 7‐day clarithromycin‐containing triple therapy is still valid as the most effective empirical first‐line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first‐line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.     

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third‐line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin‐metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI‐B‐T‐M) three times a day (tid) for 1 week. In the case of treatment failure with this second‐line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI‐B‐T‐F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI‐B‐T‐M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI‐B‐T‐F. Final cure of H. pylori with PPI‐B‐T‐F was achieved in 9/10 patients (90%) nonresponsive to PPI‐B‐T‐M. Conclusions. In the presence of metronidazole resistance, PPI‐B‐T‐M as a recommended second‐line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second‐line quadruple therapy may be best suited in case of a metronidazole‐free first line‐regimen (e.g. PPI‐clarithromycin‐amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI‐B‐T‐F combination does not have a cross‐resistance potential to metronidazole and is a promising salvage option after a failed PPI‐B‐T‐M regimen.     

Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days

Background: Bismuth‐containing quadruple therapy given twice a day for 14 days has been shown to be an excellent first‐line H. pylori eradication therapy. Aim: To compare the efficacy and tolerability of twice‐a‐day bismuth‐containing quadruple H. pylori eradication therapy for 10 versus 14 days in a noninferiority trial. Methods: Dyspeptic patients with H. pylori infection and naïve to H. pylori treatment were randomly assigned to: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg given b.i.d. (with the midday and evening meals) for 10 or 14 days. Eradication was defined by negative UBT and/or histology 4–6 weeks posttherapy. Efficacy and side effects were determined. Results: A total of 417 patients were randomized (153 men, 264 women; median age 52). Per protocol (PP) treatment success with 14 and 10 days was essentially identical [i.e., 96% (95% CI: 92–98) vs 95% (95% CI: 91–98) for 14 days versus 10 days, respectively. Results with intention‐to‐treat (ITT) analysis were also similar (92% (95% CI, 87–95) vs 92% (95% CI, 88–96)) for 14 and 10 days, respectively. Compliance was excellent in both groups. Side effects were generally mild and similar between groups. Fatigue, discomfort, and vomiting were more common in those in the 14‐day group. The 10‐day regimen costs € 17.65 (ie, approximately 25%) less than the 14‐day regimen. Conclusions: Bismuth‐containing quadruple therapy remained highly effective (i.e., ≥95% PP and >90% ITT) despite reducing the duration from 14 to 10 days.     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

A comparison between sequential therapy and a modified bismuth-based quadruple therapy for Helicobacter pylori eradication in Iran: a randomized clinical trial

Background: Sequential regimens have been recently reported to be superior to the standard triple therapies in Helicobacter pylori eradication, but most of these studies were performed in Europe and data from developing countries are lacking. So we designed a study to compare a sequential regimen with a bismuth‐based quadruple therapy that contains a short course of furazolidone, in Iran. Methods: Two hundred and ninety‐six patients with duodenal ulcer and naïve H. pylori infection were randomized into two groups: 148 patients received (PAB‐F) pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. And 148 patients received (PA‐CT) pantoprazole (40 mg‐bid) for 10 days, amoxicillin (1 g‐bid) for the first 5 days, and clarithromycin (500 mg‐bid) plus tinidazole (500 mg‐bid) just during the second 5 days. C¹⁴‐urea breath test was performed 8 weeks after the treatment. Results: Two hundred and sixty‐one patients completed the study (137 patients in the PA‐CT and 124 in the PAB‐F group). The results were not statistically different between the two groups in the eradication rates and the severity of side effects. The intention to treat eradication rate was 80.4% in the PAB‐F group and 83.7% in the PA‐CT group. Per‐protocol eradication rates were 88.7% and 89.1%, respectively. Conclusion: Because the two regimens showed acceptable and similar abilities in H. pylori eradication and because of much higher cost of clarithromycin in Iran, the furazolidone containing regimen seems to be superior. Further modifications of sequential therapies are needed to make them ideal regimens in developing countries.     

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

Background: Therapy combining a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole is widely recommended for first‐line treatment for Helicobacter pylori infection. The purpose of this study was to examine the outcomes of PPI‐containing triple therapy and identify factors influencing the cure rate of H. pylori infection in South China. Materials and Methods: H. pylori positive patients with different occupations from 25 hospitals in five provinces of South China were enrolled. They received a PPI, metronidazole and amoxicillin triple therapy for a week. H. pylori eradication was evaluated by ¹³C‐urea breath test 4 weeks after therapy. Association between H. pylori eradication with occupation, gender, age, educational level, and protocol compliance was evaluated by Logistic regression. Results: Six hundred and seventy‐five were enrolled. The intention‐to‐treat and per‐protocol analyses showed overall cure rates of 60% (95% CI = 56.3–63.7%) and 64.5% (95% CI = 60.7–68.3%), respectively. Multivariate logistic regression showed that occupation, gender and protocol compliance were positively associated with the eradication rate (p < .01). The cure rate for those who took 80% or more of the prescribed drugs was 64.5% (95% CI = 60.7–68.3%) versus 14.6% (95% CI = 6–29%, p < .001) for those who took less. Lower eradication rates were also observed in farmers and women. Conclusions: The eradication rate with a PPI, metronidazole and amoxicillin triple therapy was unacceptably low in South China. These results suggest that studies of the eradication of H. pylori infection in China must take into account antibiotic resistance as well as patient occupation, gender, and protocol compliance. Gastric cancer and peptic ulcer disease are both important in China making methods to effectively and efficiently eradicate H. pylori a priority.