Eradication of Helicobacter pylori in children in Vietnam in relation to antibiotic resistance

Background: Low Helicobacter pylori eradication rates are common in pediatric trials especially in developing countries. The aim of the study was to investigate the role of antibiotic resistance, drug dosage, and administration frequency on treatment outcome for children in Vietnam. Materials and Methods: Antibiotics resistance of H. pylori was analyzed by the Etest in 222 pretreatment isolates from children 3–15 years of age who were originally recruited in a randomized trial with two treatment regiments: lansoprazole with amoxicillin and either clarithromycin (LAC) or metronidazole (LAM) in two weight groups with once‐ or twice‐daily administration. The study design was an observational study embedded in a randomized trial. Results: The overall resistance to clarithromycin, metronidazole, and amoxicillin was 50.9%, 65.3%, and 0.5%, respectively. In LAC, eradication was linked to the strains being susceptible to clarithromycin (78.2% vs 29.3%, p = .0001). Twice‐daily dosage of proton‐pump inhibitor (PPI) and clarithromycin was more effective for eradication than once‐daily dosage for resistant strains (50.0% vs 14.7%, p = .004) and tended to be so also for sensitive strains (87.5% vs 65.2%, p = .051). Exact antibiotic dose per body weight resulted in more eradication for resistant strains (45.3% vs 8.0%, p = .006). These differences were less pronounced for the LAM regimen, with twice‐daily PPI versus once daily for resistant strains resulting in 69.2% and 50.0% eradication (p = .096), respectively. Conclusions: Helicobacter pylori clarithromycin resistance was unexpectedly high in young children in Vietnam. Clarithromycin resistance was an important cause for eradication treatment failure. Twice‐daily administration and exact antibiotic dosing resulted in more eradicated infections when the strains were antibiotic resistant, which has implications for the study design in pediatric H. pylori eradication trials.     

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.     

High Efficacy of 14‐Day Triple Therapy‐Based,Bismuth‐Containing Quadruple Therapy for Initial Helicobacter pylori Eradication

Background: The success rate of currently recommended 7‐day triple therapy with a PPI plus amoxicillin and clarithromycin has fallen into the unacceptable range. It is urgent to look for a new strategy to treat the infection of Helicobacter pylori. Aims: To observe the efficacy of triple therapy‐based, bismuth‐containing quadruple therapy for H. pylori treatment. Methods: A total of 160 patients with functional dyspepsia who were Hp+ were randomly assigned into two groups. Regimen: Omeprazole 20 mg, Amoxicillin 1.0 g, Clarithromycin 500 mg and Bismuth Potassium Citrate 220 mg, twice a day. Eighty patients received 7‐day quadruple therapy and 80 patients received the same therapy for 14 days. Six weeks after treatment, H. pylori eradication was assessed by ¹³C‐urea breath test. Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method. Results: Fourteen‐day therapy led to a significant increase of H. pylori eradication success when compared to 7‐day therapy in the intention‐to‐treat analysis (93.7 vs 80.0%; p = .01), and the per‐protocol analysis (97.4 vs 82.0%; p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin and amoxicillin were 42.1, 18.0 and 0%. Fourteen‐day therapy was significantly more effective in patients with clarithromycin‐resistant strains. Incidences of adverse events were comparable. Conclusions: Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen‐day triple therapy‐based, bismuth‐containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen.     

Vitamin C and E supplements to lansoprazole-amoxicillin-metronidazole triple therapy may reduce the eradication rate of metronidazole-susceptible Helicobacter pylori infection

Aim. To test whether vitamin C and E supplements to triple therapy can improve the Helicobacter pylori eradication rate and gastric inflammation. Methods. A total of 104 H. pylori‐infected patients were randomized to receive: either lansoprazole, amoxicillin, and metronidazole twice daily for 1 week (triple‐only group) or lansoprazole, amoxicillin, metronidazole plus vitamin C (250 mg) and vitamin E (200 mg) twice daily for 1 week, followed immediately by vitamin C and E once daily for 6 consecutive weeks (triple‐plus‐vitamin group). Eight weeks after the completion of triple therapy, patients were assessed for the effectiveness of H. pylori eradication. The severity of gastric inflammation in histology was assessed for the acute and chronic inflammation scores. Results. Intention‐to‐treat and per‐protocol eradication rates were 59.1% and 64.4% in the triple‐only group, and 40% and 44% in the triple‐plus‐vitamin group. In the patients infected with metronidazole susceptible isolates, the triple‐only group had a higher intention‐to‐treat eradication rate than those in the triple‐plus‐vitamin group (80% vs. 53.1%, p < .01). However, for the metronidazole resistance isolates, the intention‐to‐treat eradication rates between the two groups were not different (26.3% vs. 21.7%, p = NS). The improvements of both acute and chronic inflammation scores in histology were not different between the two groups. Conclusion. Adding vitamin C and E to triple therapy cannot improve the H. pylori eradication rate and gastric inflammation. For patients with metronidazole susceptible strain infection, adding these vitamins may even reduce the eradication rate of triple therapy.     

Lafutidine,a novel histamine H2-receptor antagonist,vs lansoprazole in combination with amoxicillin and clarithromycin for eradication of Helicobacter pylori

Background. In contrast to the growing amount of data concerning proton pump inhibitor‐based triple therapy for Helicobacter pylori infection, it is still controversial whether proton pump inhibitor can be replaced by H₂ receptor antagonist without compromising efficacy. Lafutidine is a novel potent H₂ receptor antagonist with gastroprotective activities such as enhancement of gastric mucosal blood flow. Methods. 122 outpatients with positive cultures and subsequent successful cultivation of H. pylori for antimicrobial susceptibility tests were randomized to receive a 7‐day course of either lafutidine (20 mg twice daily) or lansoprazole (30 mg twice daily), plus clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Eradication was considered successful if the rapid urease test, culture, histology and [ 13 ]C‐urea breath test were all negative at least 4 weeks after cessation of therapy. Cytochrome p450 2C19 genotype status using polymerase chain reaction‐restriction fragment length polymorphism was also studied. Results. On intention‐to‐treat basis, H. pylori cure was achieved in 52 of 61 (85.2%) patients and 49 of 61 (80.3%) patients for the lafutidine‐ and lansoprazole‐based therapies, respectively. The predicted 95% confidential intervals for the 4.9% of the difference were ?1.8–11.6%. Using per protocol analysis, the eradication rates were 88.2% (52/59) and 84.5% (49/58), respectively. The predicted 95% confidential intervals for the 3.7% of the difference were ?2.6–10.0%. Adverse events were observed in five and six patients, from the lafutidine and lansoprazole groups, respectively, but they were generally mild. Genetic predisposition of cytochrome p450 2C19 had no significant influence on treatment outcome in both regimens. Conclusions. The lafutidine‐clarithromycin‐amoxicillin therapy yielded satisfactory results for eradicating H. pylori, which was comparable with those of the lansoprazole‐based regimen with the same drug combination.     

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.     

Lafutidine versus Lansoprazole in Combination with Clarithromycin and Amoxicillin for One versus Two Weeks for Helicobacter pylori Eradication in Korea

Background and Aims: Lafutidine is a novel H₂‐receptor antagonist with gastroprotective activity that includes enhancement of gastric mucosal blood flow. The aim of the present study was to test the efficacy of 7‐ or 14‐day lafutidine–clarithromycin–amoxicillin therapy versus a lansoprazole‐based regimen for Helicobacter pylori eradication. Methods: Four hundred and sixty‐three patients with H. pylori‐infected peptic ulcer disease were randomized to one of four regimens: (1) lafutidine (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LFT group) or (2) for 14 days (the 14LFT group); (3) lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LPZ group); or (4) for 14 days (the 14LPZ group). The eradication rates, drug compliance, and adverse effects among the four regimens were compared. Results: The eradication rates by the intention‐to‐treat and per‐protocol analyses in the 7LFT and 7LPZ groups were 76.5% and 81.6%, and 76.9% and 82.0% (p = .94 and .95), respectively. The eradication rates by intention‐to‐treat and per‐protocol analyses in the 14LFT and 14LPZ groups were 78.2% and 82.2%, and 80.4% and 85.9% (p = .70 and .49), respectively. The treatment duration for 7 days or 14 days did not affect the eradication rates. In addition, the adverse effect rates and discontinuation rates were similar among the four groups. Furthermore, the ulcer cure rate and symptom response rate were similar in the lafutidine and lansoprazole groups. Conclusion: The results of this study showed that lafutidine–clarithromycin–amoxicillin therapy was a safe and effective as lansoprazole‐based triple therapy for the eradication rate of H. pylori, and could be considered as an additional treatment option.     

Amoxicillin/tetracycline combinations are inadequate as alternative therapies for Helicobacter pylori infection

Background. Triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are the present gold standards for cure of Helicobacter pylori infection. However, primary resistance to either clarithromycin or nitroimidazole derivatives is increasing and alternative therapies are needed. Aim. To determine the efficacy and safety of three regimens consisting of amoxicillin and tetracycline or doxycycline combined with either lansoprazole or ranitidine bismuth citrate. Methods. Two hundred and seventy H. pylori infected patients were randomly given one of the following treatments: amoxicillin 1 g twice a day (b.i.d.) plus tetracycline 500 mg four times a day (q.i.d.) with either lansoprazole 30 mg b.i.d. (group LAT) or ranitidine bismuth citrate 400 mg b.i.d. (group RBCAT) for 7 days and amoxicillin 1 g b.i.d. plus doxycycline 100 mg b.i.d. and lansoprazole 30 mg b.i.d. for 14 days (group LAD). Eradication rate was assessed by UBT at 4–6 weeks after therapy. Results. The three groups (LAT, RBCAT, and LAD) of patients achieved eradication rates of 35% (25–45), 20% (12–29) and 36% (25–46), respectively, on intention‐to‐treat analysis. Patient compliance was optimal and side‐effects minimal in all three groups. Conclusions. Although the amoxicillin/tetracycline combination is attractive (inexpensive, safe, and with low primary resistance rate), it can not be recommended for H. pylori eradication.     

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.     

Helicobacter pylori antimicrobial resistance in a pediatric population

Background

The increasing prevalence of Helicobacter pylori (H. pylori) antimicrobial resistance, primarily for clarithromycin decreases the success of treatment. The aim of this study is to determine the local pattern of first‐line antimicrobials resistance and the eradication rate.

Material and Methods

Prospective cohort study of H. pylori infected patients (positive histological or cultural exams) treated at Centro Materno‐Infantil do Norte from January of 2013 to October of 2017. Susceptibility to 4 antibiotics: amoxicilin, metronidazole, clarithromycin, and levofloxacin were analyzed by E‐test (phenotypic resistance). The E‐test was chosen because it is simple and cost‐effective for routine susceptibility testing. Point mutations that confer clarithromycin resistance were surveyed (genotypic resistance). Eradication of H. pylori infection was defined by a negative urea breath test or fecal antigen 6‐8 weeks after the end of treatment.

Results

Of a total of 74 H. pylori infected patients, 16 were excluded because they had previous H. pylori treatment or severe systemic disease. Median age of infection cases was 15 years (3‐17 years). Eradication regimen used in all patients combined the use of 3 antibiotics (amoxicillin and metronidazole or clarithromycin) and proton pump inibhitor for 14 days and was tailored according antimicrobial susceptibility. 79.5% of the patients completed the treatment. The resistance rate for metronidazole and clarithromycin was 3.3% and 23.3%, respectively. There was no resistance for amoxicilin and levofloxacin. The rate of genotypic resistance to clarithromycin was 37.2%. The eradication rate was 97.8%.

Conclusions

The authors found a high resistance rate of H. pylori for clarithromycin in this northern portuguese pediatric center. This factor should determine a change in local current treatment, contraindicating the use of clarithromycin as a first‐line treatment for H. pylori infection in children. The high eradication rate maybe explained for the eradication treatment tailored according antimicrobial susceptibility.     

One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin

Aim: To investigate a 1‐week once‐daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection. Methods: Consecutive patients (n = 103) with at least one previous treatment failure and H. pylori infection resistant to both metronidazole and clarithromycin were treated with esomeprazole 40 mg, moxifloxacin 400 mg, and rifabutin 300 mg, given once daily for 7 days. Eradication was confirmed by histology and culture. CYP2C19 status was determined by polymerase chain reaction‐restriction fragment length polymorphism. Results: Intention‐to‐treat and per‐protocol eradication rates were 77.7% (68.4–85.3) and 83.3% (74.4–90.2). Five patients discontinued prematurely (4.8%). Eradication was achieved in 93.1% of poor/intermediate metabolizers and in 78.8% of homozygous extensive metabolizers (p = .14). Eradication rates in patients with one, two, three, and four or more previous failures were 78.3%, 89.6%, 68.6%, and 88.9%, respectively (p = .21). The regimen was effective in seven of nine patients who previously failed quadruple therapy. Post‐treatment resistance to moxifloxacin and rifabutin was detected in two (12.5%) and five (31%) patients after treatment failure. Conclusion: Once‐daily triple therapy with esomeprazole, moxifloxacin, and rifabutin is a promising, safe, and convenient regimen for rescue therapy of H. pylori infection that may serve as a valuable alternative to quadruple therapy, particularly for patients with intolerance to amoxicillin.     

Comparison of amoxicillin-metronidazole plus famotidine or lansoprazole for amoxicillin-clarithromycin-proton pump inhibitor treatment failures for Helicobacter pylori infection

BACKGROUND: Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor. MATERIALS AND METHODS: Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second-line therapy including metronidazole: a 7-day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7-day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin. RESULTS: Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains were found. The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively. CONCLUSIONS: Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health-care costs is also anticipated.     

Low efficacy of clarithromycin including sequential regimens for Helicobacter pylori infection

Background: Sequential treatment for Helicobacter pylori (H. pylori) appears to achieve a better eradication rate than triple therapy. However, most of the data have been reported from the Italy, and studies from different population are needed before it is recommended in clinical practice. The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods: Consecutive H. pylori ‐positive patients with non‐ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA‐CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA‐CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results: A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention‐to‐treat (“ITT”) eradication rates were 74.3% and 66.5% in all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA‐CT group than LA‐CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was comparable. Conclusion: Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey.     

Eradication of Helicobacter pylori Using One-week Triple Therapies Combining Omeprazole with Two Antimicrobials: The MACH I Study

Background. Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established.
Materials and Methods. We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom. Patients (n=787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following anti-microbials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M). Eradication of H. pylori was evaluated by ¹³C-UBT, performed before and 4 weeks after treatment cessation.
Results. The eradication rates for the all-patients-treated analysis were 96%. OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP. OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90%. All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events.
Conclusions. Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance. The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.     

Efficacy of 2-week, second-line Helicobacter pylori eradication therapy using rabeprazole, amoxicillin, and metronidazole for the Japanese population

Background: Following the failure of first‐line Helicobacter pylori eradication therapy using a proton pump inhibitor, amoxicillin, and clarithromycin, second‐line therapy is conducted for 1 week using metronidazole instead of clarithromycin in Japan. Recent studies indicate that metronidazole‐containing therapy has a higher eradication rate with prolonged treatment duration, even with metronidazole resistance. The aim of this study was to reveal the efficacy of 2‐week metronidazole‐containing second‐line therapy. Methods: Eighty‐two consecutive outpatients who had failed in the first‐line eradication therapy were enrolled and second‐line therapy was initiated with 10 mg rabeprazole, 750 mg amoxicillin, and 250 mg metronidazole twice daily. After they had been screened by hematological examination 1 week after initiation, the treatment was continued for 2 weeks after initiation in patients without hematological abnormality. Cure was essentially confirmed by the urea breath test. Results: After one patient was lost, hematological examination showed elevated serum aminotransferase in 14 of 81 patients. Although it was mild without clinical issues, they were ethically excluded from this study. In the remaining 67 patients and the lost patient, the eradication rate with 2‐week therapy was 65/68 (96%, 95% confidence interval: 88–98%) by intention to treat analysis and 65/65 (100%, 94–100%) by per protocol analysis. The main adverse event was soft stools (39%), and no serious adverse event was observed. Conclusion: This 2‐week metronidazole‐containing second‐line therapy provides high efficacy in Japan where metronidazole resistance is rare.     

Antibiotic resistance of Helicobacter pylori in Mazandaran, North of Iran

Background: The aim of this study was to investigate the prevalence of resistances in Helicobacter pylori against commonly used antibiotics including metronidazole, clarithromycin, amoxicillin, and tetracycline in Iranian patients. Methods: H. pylori isolates were collected from gastric biopsies from patients referred for upper gastrointestinal endoscopy at Tooba Medical Center, Sari, Iran, from 2007 to 2010. None of them had been using antibiotics for at least 8 months. H. pylori was identified based on morphological shape and positive biochemical tests for catalase, oxidase, and urease activity. Antibiotic resistance for metronidazole, clarithromycin, amoxicillin, and tetracycline was investigated by using epsilometer test. Resistance was defined by minimal inhibitory concentration (MIC) > 0.5 mg/L for amoxicillin (AMX), >4 mg/L for tetracycline (TET), >8 mg/L for metronidazole (MTZ), and >1 mg/L for clarithromycin (CLR). Results: Strains were collected from 132 patients, mean age 45.8 years, 52 (39%) were women. Patients had diverse diagnoses: gastritis 42 (31.8%), duodenal ulcer 45 (34%), gastric cancer 15 (11.3%), or gastric ulcer 30 (22.7%). The prevalences of resistance of H. pylori strains isolated from the patients were 73.4% for metronidazole, 30% for clarithromycin, 6.8% for amoxicillin, and 9% for tetracycline. Twenty‐eight (21.2%) were double resistant to MTZ‐CLR, 16 (12.1%) showed triple resistance to MTZ‐CLR‐AMX, and 8 (6%) were resistant to all four tested antibiotics (MTZ‐CLR‐AMX‐TET). No associations were detected between multiple resistant strains and clinical manifestations (p > .05). Conclusions: The prevalence of H. pylori antibiotic resistance to metronidazole and clarithromycin was high in Iran consistent with the reported low success rates for H. pylori treatment in this country.     

Pilot studies to identify the optimum duration of concomitant Helicobacter pylori eradication therapy in Thailand

Background and Aim: Eradication rate for Helicobacter pylori infection with standard triple therapy has globally declined including in Thailand, and new regimens are required that provide reliable high eradication rates. The study was designed to determine whether concomitant therapy administered for either 5 or 10 days would produce a ≥ 95% (grade A) treatment success in H. pylori infected Thai subjects with nonulcer dyspepsia. Methods: Two prospective, but separate, pilot single‐center studies were carried out during September 2009–December 2010 at Thammasat University Hospital, Thailand. H. pylori infected subjects were randomized into the two pilot studies; either 5‐day or 10‐day concomitant therapy. Thai concomitant therapy consisted of rabeprazole (20 mg) twice daily, amoxicillin 1 g twice daily, metronidazole 400 mg three times a day, and clarithromycin MR 1 g once daily. H. pylori status was assessed by ¹³C‐urea breath test 4 weeks after completion of the treatment. Successful treatment was defined as achieving a grade A result (≥95%) and failure by <90% cured. Results: A total of 110 subjects were randomized (55 to the 5‐day treatment trial and 55 to the 10‐day regimen). Baseline subject demographic and clinical characteristics were similar in both studies. All subjects completed their assigned therapies. The 10‐day concomitant treatment trial was successful in 53 of the 55 subjects (96.4%; 95% CI 87.4–99.5%). The 5‐day concomitant pilot was judged to be a failure as only 49 of 55 subjects (89.1%; 95% CI = 77.7–95.8%) were cured. The frequency of adverse events was low and similar in the two studies. Conclusion: The 10‐day concomitant regimen provided excellent treatment success (eradication rate >95%) and was well tolerated. Ten‐day concomitant therapy is likely to become useful first‐line H. pylori eradication in Thailand.     

The HOMER Study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection

Background. Helicobacter pylori eradication with omeprazole, amoxycillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxycillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed. Methods. Patients (n = 394) with a positive H. pylori screening test result and endoscopy‐proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxycillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a ¹³C urea breath test and a culture. Eradication was defined as two negative ¹³C‐urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy. Results. The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per‐protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxycillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%–39% in the five countries). The overall eradication rate in prestudy metronidazole‐susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; p < .001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance. Conclusions. H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.     

The relationship between consumption of antimicrobial agents and the prevalence of primary Helicobacter pylori resistance

Background. Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies. We assessed the primary antibiotic resistance rates of H. pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti‐H. pylori therapy in Japan. Materials and Methods. Antibiotic susceptibility was tested using the agar dilution method for clarithromycin, amoxicillin and metronidazole. Isolates were considered resistant when the MIC value was > 8 mg/l for metronidazole, > 1 mg/l for clarithromycin and < 0.5 mg/l for amoxicillin. Results. Helicobacter pylori isolates were obtained from 593 Japanese patients from 1995 to 2000. Primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin was found in 11%, 9% and 0.3% strains, respectively. The proportion with clarithromycin resistance significantly increased from 7% in 1997–98 to 15.2% in 1999–2000 (p = .003). During the same period the metronidazole resistance rate also increased from 6.6% in 1997–98 to 12% in 1999–2000 (p = .02). The prevalence of clarithromycin and metronidazole was related to the annual consumption of these antimicrobial agents. Conclusion. Resistance rates for both clarithromycin and metronidazole appear to reflect the annual consumption of these agents. The high rate of clarithromycin resistance in Japan suggests that the effectiveness of clarithromycin‐based therapies may be compromised in the near future.     

Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India

Background. In developed countries, a 1-week regimen of combined proton pump inhibitors and two antibiotics is considered adequate for Helicobacter pylori eradication. However, there is a paucity of reports from developing countries on treatment duration of less than 14 days. We compared efficacy of 7 and 14 days of lansoprazole (L), clarithromycin (C), and amoxicillin (A) combinations for eradication of H. pylori.
Patients and Methods. Forty-six consecutive patients who presented with upper gastrointestinal symptoms and tested positive for H. pylori infection were included in the study. In every patient, after performance of upper gastrointestinal endoscopy, antral biopsies were obtained. H. pylori infection was diagnosed by positive rapid urease test and identification of organisms on antral histology. Patients were randomly selected to receive lansoprazole, 30 mg once daily, plus clarithromycin, 250 mg twice daily, plus amoxicillin, 500 mg three times daily for 2 weeks ( group 1; n = 24; age , 36 ± 12 years ; 18 men ) or 1 week ( group 2; n = 22; age , 45 ± 15 years ; 12 men ). One month after completion of treatment, repeat upper gastrointestinal endoscopy was performed. H. pylori eradication was defined as absence of organism on histopathological examination of both antrum and body of stomach and negative rapid urease test.
Results. Eradication rate was higher in group 1 (23 of 24; 96%) as compared to group 2 (12 of 22; 54%; p < .05). One patient in group 1 had diarrhea, and one patient in group two had skin rash and itching.
Conclusions. Fourteen-day therapy with lansoprazole, clarithromycin, and amoxicillin is highly effective in eradication of H. pylori. Reducing duration of therapy to 7 days significantly lowers eradication rates.