Amoxicillin Triple Therapy Research Articles

Comparison of Risk and Severity of Helicobacter Pylori Infection in Non-Native Versus US Native Pediatric Patients.

Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients. We retrospectively reviewed all endoscopies with patients aged 1-21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations. In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients. Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.

Comparison of Levofloxacin Triple Therapy and Amoxicillin Triple Therapy in the Treatment of Peptic Ulcer

Comparison of Levofloxacin Triple Therapy and Amoxicillin Triple Therapy in the Treatment of Peptic Ulcer

Outcomes of a Randomized Controlled Trial Comparing Modified High Dose Omeprazole and Amoxicillin Triple Therapy with Standard Triple Therapy for Helicobacter Pylori Eradication

Background:Helicobacter pylori (H. pylori) infection is related to peptic ulcer diseases and gastric cancer and eradication of H. pylori should be expected to decrease the risk of their development. Factors affecting H. pylori eradication are antibiotic resistance, CYP2C19 genotypes, drug regimen and patient compliance. Increment of omeprazole and amoxicillin dosage in clarithromycin-containing triple therapy regimen may overcome these problems and may be a better choice than the conventional clarithromycin-containing triple therapy regimen.Objective:To compare the eradication rates with modified triple therapy (MTT) and standard triple therapy (STT) as first-line treatment.Materials and Methods:The study was an open label, multicenter, randomized controlled trial. A total of 170 patients infected with H. pylori diagnosed by rapid urease test were randomly assigned into 2 groups. The first was treated with a 14-day MTT (20 mg omeprazole t.i.d., 500 mg amoxicillin t.i.d., and 500 mg clarithromycin b.i.d.) and the second with a 14-day STT (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 500 mg clarithromycin b.i.d.). H. pylori eradication was evaluated by 14C-urea breath test. CYP2C19 genotypes, clarithromycin resistance, side effects and patient compliance were also recorded.Results:There were 85 patients in each group. The H. pylori eradication rate in the MTT group was 84.7% by ITT analysis and 91.1% by PP analysis, compared to the STT group values of 76.5% and 87.8% (p = 0.18 and 0.51), respectively. CYP2C19 genotypes and patient compliance were similar in both groups. Prevalence of clarithromycin resistance was 7.0%. Side effects were all mild with no significant differences between the twogroups.Conclusions:MTT is not superior to STT. From this study, MTT may not be recommended as the first-line treatment for H. pylori infection in Thailand because eradication rates proved to be less than 90% by ITT analysis.

Reply to letter to the editor: “The dosage of rifabutin in H. pylori eradication regimen should be appropriately determined in each area of the world”

We appreciate the interest of Losurdo et al.1 in our paper entitled “Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study.”2 We agree with them in terms of the importance of confirming tuberculosis status before starting rifabutin therapy, including the regimen, and the assurance of empirical rescue regimens especially in third- or fourth-line treatment. Losurdo et al.1 raised concerns regarding the accuracy of the eradication rates we reported (83.3% in the 10-day group and 94.1% in the 14-day group with intention to treat) because recent studies show lower success rates (60%–80%) in relation to drug dose and treatment duration. There are few reports of rifabutin-containing regimen from Asia, while most of the reports are from Europe.3 Meanwhile, Wong et al.4 showed a 91% eradication rate and a 58% adverse-events rate with a rifabutin-containing regimen in China.4 Both of the Asian eradication rates are higher than those in previous reports.3 Rifabutin is metabolized and eliminated mainly by the CYP3A pathway and is a moderate inducer of CYP3A4 activity.5 Yamaori et al.6 revealed the difference between Japanese and Caucasian populations in the expression levels of messenger RNA (mRNA) for CYP3A4. Thus, we should determine the appropriate dosage of rifabutin because 300 mg per day may be a very high dose for Asian patients. Although Losurdo et al.1 described rifabutin 150 mg b.i.d. as low dose in their quadruple therapy, the daily dose was the same as that in our clinical trial (300 mg q.d.).2 Furthermore, Perri et al.7 also showed that the triple therapy (pantoprazole 40 mg b.i.d., amoxicillin 1 g b.i.d., and rifabutin 300 mg q.d. for 10 days) was more effective and well tolerated than the quadruple therapy (pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. for 10 days) (eradication rates: 86.6% vs. 66.6%, respectively). Therefore, it could not be determined whether the quadruple therapy is better than the rifabutin plus amoxicillin triple therapy. Losurdo et al.1 indicated that the amoxicillin resistance rate of our study (55%) is higher than the global rate.8 Although a broad international consensus has been formed about the cut-off points for antimicrobial resistance of clarithromycin and metronidazole, the cut-off point of amoxicillin has not been determined. In addition, the cut-off point of amoxicillin differs in each report (minimum inhibitory concentration (MIC) range 0.06–8 µg/ml).8–10 Therefore, the amoxicillin resistance rate of our clinical data is simply not designated as high because most of the MICs of amoxicillin in our report were less than 1 µg/ml.2 We previously reported about the enhancement of amoxicillin resistance after unsuccessful eradication.11 Therefore, we can partially understand the opinion of Losurdo et al.1 that it would be reasonable to avoid drugs that have already been used in previously unsuccessful regimens.

Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

To investigate the drug interactions between ilaprazole, a new proton pump inhibitor, and clarithromycin following ilaprazole, clarithromycin and amoxicillin combination therapy. Twelve healthy Chinese volunteers were recruited in a randomized, open-label, 3-period crossover study. All subjects were administered ilaprazole (5 mg), clarithromycin (500 mg) or a triple therapy, including ilaprazole (5 mg), clarithromycin (500 mg) and amoxicillin (1 g), twice daily for 6 consecutive days. On the 7th day, the drugs were given once, and blood samples were collected and analyzed using a well-validated HPLC/MS/MS method. Following the triple therapy, the peak concentration (C(max)) and the area under the concentration-time curve from 0 h to 12 h (AUC(0→12)) of ilaprazole were significantly decreased, as compared with the single medication group (C(max):1025.0±319.6 vs 1452.3±324.6 ng/mL; AUC(0→12): 9777.7±3789.8 vs 11363.1±3442.0 ng·h/mL). Similar changes were found for ilaprazole sulfone (C(max): 5.9±0.5 vs 9.3±1.7 ng/mL; AUC(0→12): 201.4±32.1 vs 277.1±66.2 ng·h/mL). The triple therapy significantly elevated the C(max) of clarithromycin (3161.5±702.2 vs 2541.9±476.2 ng/mL). The H pylori eradication therapy with clarithromycin, amoxicillin and ilaprazole may cause pharmacokinetic interactions that decrease the amount of ilaprazole and its metabolites and elevate that of clarithromycin.

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

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. 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 (13)C-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. 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. 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.

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second‐line treatment of resistant Helicobacter pylori infection

To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.

Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia

The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori (H. pylori). This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved >/=4 points on the dyspepsia summary score. A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.

Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia

Objectives The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori ( H. pylori). Methods This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved ≥4 points on the dyspepsia summary score. Results A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. Conclusions There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.

The Effect of Eradication of Helicobacter pylori upon the Duodenal Ulcer Recurrence -A 24 month follow-up study-

ObjectivesTo evaluate the effect of eradication of Helicobacter pylori(H.pylori) in the patients with duodenal ulcer(Du) upon the DU recurrence.MethodsThis study was performed for 190 patients with DU. Four different methods-microscopy of Gram stained mucosal smear, specific culture, biopsy urease test, histology of H&E staining-were taken for identifying colonization of H. pylori before treatment, and for finding the eradication of H. pylori 4 weeks after completion of therapy in each treatment group (cometidine, omeprazole, colloidal bismuth subcitrate(CBS), CBS and metronidazole double therapy, CBS. metronidazole and amoxicillin triple therapy). To detect DU recurrence, the gastroscopy was performed at 6, 12, 18, and 24 months after therapy.ResultsThe eradication rate of the cimetidine group, the omeprazole group, and the CBS group were 0%, 7.7%, 0%, respectively, and that of the double therapy group and the triple therapy group were 44.4% and 89.3%, respectively. Seventy three patients who were followed up for 2 years were categorized into two groups according to the eradication of H. pylori. The recurrence rate was 3.2% both in 1 year and 2 years later in the former group-one consisting of 31 patients with H. pylori eradicated, while the recurrence rate was 57.1% in 1 year and 78.6% in 2 years later, in the latter group-the other of 42 patients with H. pylori not eradicated.ConclusionThe eradication of H. pylori in patients with DU reduces the recurrence of DU.