Efficacy of a new nutraceutical formulation: L-tryptophan, probiotics, charcoal, chamomile, mint, and licorice (COLONIR®) in the improvement of gastrointestinal symptoms in subjects with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. IBS is characterized by recurrent chronic abdominal pain and altered bowel habits in the absence of organic damage. Although there are reviews and guidelines for treating IBS, the complexity and diversity of IBS presentation make treatment difficult. Treatment of IBS focuses on relieving symptoms as mild signs and symptoms can often be controlled by managing stress and by making changes in diet and lifestyle. The use of nutraceutical compounds has been advocated as a possible alternative treatment in patients with IBS. COLONIR® (Omega Pharma Srl, Milan, Italy) may be an alternative or adjuvant treatment in patients with gastrointestinal symptoms. This study aimed to evaluate the effect of this new nutraceutical formulation in inducing symptoms remission and improve gastrointestinal habits. METHODS: An initial cohort of 1004 consecutive patients referred to 25 different Units of Internal Medicine a/o Gastroenterology in Italy to perform colonoscopy for intestinal symptoms was asked to participate. Patients were treated for 2 months with two doses of nutraceuticals/day during meals namely COLONIR®. Patients were assessed at baseline and after 2 months to evaluate the frequency and severity of gastrointestinal symptoms in the past seven days with a questionnaire based on ROMA IV criteria. RESULTS: After 2 months, 899 patients completed the follow-up. COLONIR® achieved a statistically significant reduction of severity of symptoms in the study population without any documented side effects. CONCLUSIONS: These promising results, here reported, need to be confirmed, valuating the efficacy of COLONIR® in relieving gastrointestinal symptoms in IBS patients in further studies.

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review.

Background: Primary antibiotic resistance in Helicobacter pylori (H. pylori) strains is increasing worldwide, affecting therapy success. The use of therapies tailored on susceptibility pre-testing at culture has been proposed, but data are still conflicting. Method: We performed a systematic review to evaluate the role of a culture-based therapeutic approach for H. pylori treatment, taking into account the sensitivity of culture and the success rates achieved with tailored therapies in different therapeutic steps. Results: We analyzed data from 51 studies. Overall, H. pylori strains were isolated in 80.7% of 7889 patients, the success rates being 78.1%, 77.5%, 86.3% and 86.6%, before first-, second-, third-line or more therapies, respectively. In comparative studies, the infection was cured in 89.9% of 2052 patients treated with tailored therapies, and in 77.6% of 2516 patients receiving empiric therapy (P<0.001). However, in the subanalysis, the tailored approach achieved optimal eradication rates (>90%) only when it was applied before first- and second-line therapies, but not before third-line or more attempts (<80%). Moreover, no significant difference emerged between the 2 approaches when data from only the most recent (last 5 years) studies were considered, as well as in those performed in Western populations. Conclusions: The attempt to achieve antibiotic susceptibility testing before treatment failed in 20% of infected patients managed in dedicated laboratories. Culture-tailored therapies administered after 2 or more therapies achieved suboptimal eradication rates. The role of bacterial culture in patients whose therapeutic management failed to eradicate H. pylori probably needs to be corroborated by further data.

Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013-2020: Results of the European Registry on H. pylori Management (Hp-EuReg).

Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013-2016 to 2017-2020. Concerning naïve patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013-2016 (33%) and 2017-2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naïve patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013-2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.

Helicobacter pylori eradication following first-line treatment failure in Europe: What, how and when chose among different standard regimens? A systematic review.

Cure rate following standard first-line regimens for Helicobacter pylori eradication is decreasing so several patients require two or more treatments. Antibiotic susceptibility-based therapy, advised in current guidelines, is largely impracticable in clinical practice. Some 'standard' regimens (triple therapies based on either levofloxacin or rifabutin, bismuth-based quadruple therapies, sequential, concomitant and hybrid therapies) were empirically used as rescue therapies. We performed a systematic review on recent studies carried out in European countries dealing with these regimens. A total of 24 studies, with 3804 patients, were identified. As second-line therapy, Pylera (89.2%) and sequential therapy (92.5%) achieved significantly higher cure rates as compared to all the other regimens. As third-line therapy, levofloxacin-based therapy (84.1%) and Pylera (83.6%) achieved similarly high cure rates, whereas standard, bismuth-based quadruple therapy (64.1%) achieved the lowest. As a rescue therapy, the success rate was close to 75% following all therapies used, with data on rifabutin-based regimen consolidated in the larger sample size. Overall, levofloxacin-amoxicillin triple therapy achieved higher eradication rates when the 14- rather than 10-day regimen was used (87.1 vs. 72.2%; P = 0.003). Among bismuth-based therapies, Pylera achieved a significantly higher eradication rate than standard quadruple therapy (88 vs. 67%; P < 0.0001). These data suggest that a wise 'therapeutic package' following first-line therapy could be Pylera, levofloxacin- and rifabutin-based therapy, as long as Pylera therapy was not used as a first-line regimen and levofloxacin-based regimen was administered for 14 days.

Rescue Therapies for Helicobacter pylori Infection in Foreign Patients Treated in Italy.

MATERIALS AND METHODS: Consecutive foreigner patients with H. pylori infection following at least one therapy failure were enrolled. All patients underwent upper endoscopy with gastric biopsies used for both histologic examination and culture/susceptibility test. Rescue therapies administered accordingly to susceptibility testing were rifabutin-based therapy, levofloxacin-based therapy, sequential. Pylera was prescribed regardless the resistance pattern. RESULTS: A total of 103 (M/F: 27/76, mean age: 41.9 y, range: 18 to 85) were enrolled. The overall resistance rates toward clarithromycin, metronidazole, and levofloxacin were 76.7%, 66%, and 42.7%, respectively, with triple resistance present in 33.9% of bacterial isolates. Eradication rates were 71.4% on 40 patients for rifabutin-based therapy, 82.8% on 42 cases for levofloxacin-based therapy, 75% on 11 patients treated with sequential therapy, and 100% on 10 cases who received Pylera regimen. CONCLUSIONS: To our knowledge, this is the first study assessing H. pylori eradication rates in foreigner patients, who failed at least one therapeutic attempt, managed in Italy. Even by using a culture-based approach, the infection was not cured in a definite number of patients.

Rifabutin-Based Triple Therapy Or Bismuth-Based Quadruple Regimen As Rescue Therapies For Helicobacter pylori Infection.

BACKGROUND/AIMS: H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies. METHODS: Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated. RESULTS: Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present. CONCLUSIONS: Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®.

Role of MIC levels of resistance to clarithromycin and metronidazole in Helicobacter pylori eradication.

OBJECTIVES: Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy. METHODS: This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole). RESULTS: Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains. CONCLUSIONS: We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics.

Pylera and sequential therapy for first-line Helicobacter pylori eradication: a culture-based study in real clinical practice.

BACKGROUND AND AIMS: Italian guideline suggests 10-day sequential or bismuth-based quadruple therapies for first-line Helicobacter pylori treatment. Comparison between these regimens is lacking. We assessed the efficacy of these therapies in clinical practice and evaluated the role of primary bacterial resistance toward clarithromycin and metronidazole. PATIENTS AND METHODS: Consecutive patients with H. pylori infection were enrolled. Bacterial culture with antibiotics susceptibility testing was attempted in all cases. Patients received either a sequential therapy with esomeprazole 40 mg for 10 days plus amoxicillin 1000 mg for the first 5 days followed by clarithromycin 500 mg and tinidazole 500 mg (all twice daily) for the remaining 5 days, or bismuth-based therapy with esomeprazole 20 mg twice daily and Pylera 3 tablets four times daily for 10 days. H. pylori eradication was assessed by using C-urea breath test. RESULTS: A total of 495 patients were enrolled. Following sequential (250 patients) and quadruple (245 patients) therapies, the eradication rate were 92 and 91%, respectively, at intention-to-treat analysis and 96 and 97%, respectively, at per protocol analysis. Overall, the pattern of bacterial resistance did not significantly affect the cure rate, but the presence of clarithromycin and metronidazole dual resistance tended to reduce the success rate of both sequential (84.8 vs. 90.1%; P=0.4) and quadruple (85 vs. 94.1%; P=0.06) therapies. Adverse events occurred more frequently with the quadruple than with sequential therapy (56.9 vs. 25.8%; P<0.001). CONCLUSION: In our country, sequential and bismuth-based quadruple therapy achieved similarly high eradication rates as first-line treatments for H. pylori infection in clinical practice.

Rifabutin Triple Therapy is Effective in Patients With Multidrug-resistant Strains of Helicobacter pylori.

INTRODUCTION: Eradicating Helicobacter pylori continues to be a challenge, and no treatment regimen is uniformly successful in all treated patients. Triple therapy with rifabutin and amoxicillin is a successful rescue therapy after consecutive treatment failures. We designed this study to test the efficacy of 12-day rifabutin-based triple therapy in patients infected with multidrug-resistant strains. METHODS: Consecutive patients with dyspeptic symptoms after at least 1 antibiotic therapy course for H. pylori infection harboring triple-resistant (clarithromycin, metronidazole, levofloxacin) strains were enrolled. They received triple therapy with esomeprazole 40 mg bid, amoxicillin 1 g bid, and rifabutin 150 mg od for 12 days. Patients who failed rifabutin therapy were treated empirically on the basis of the judgment of the treating physician. RESULTS: A total of 254 out of 756 tested patients were found to be infected with a triple-resistant H. pylori strains after at least 1 antibiotic therapy course. Overall, the infection was eradicated in 213 patients, corresponding to a cure rate of 82.9% (95% CI, 78.3-87.5) by intention-to-treat analysis and 88.7% (95% CI, 84.7-92.7) at per-protocol analysis. In multivariate analysis, no factor was identified as an independent predictor of bacterial eradication. CONCLUSIONS: There is no current standard for the growing population of patients with multidrug-resistant strains of H. pylori. The 12-day low-dose rifabutin/high-dose proton pump inhibitor regimen is a safe and reliable option for patients infected with triple-resistant strains.

Culture-based selection therapy for patients who did not respond to previous treatment for Helicobacter pylori infection.

BACKGROUND & AIMS: Eradication of Helicobacter pylori using empiric therapy has become difficult as a result of increasing resistance to antibiotics. We evaluated the efficacy of specific treatments, selected based on response of bacterial samples to culture with clarithromycin, levofloxacin, and metronidazole, for patients infected with resistant strains of H pylori. METHODS: We performed a prospective study at a single center of 236 consecutive patients with persistent H pylori infection, despite 1 or more treatment attempts, and documented resistance to at least 1 antimicrobial agent (based on bacterial culture tests). Biopsy samples were collected by endoscopy and cultured in selective media. Patients received either 10 days of levofloxacin (250 mg twice daily for 131 patients with susceptible infections) or 12 days of rifabutin (150 mg once daily for 105 patients resistant to levofloxacin) in combination with amoxicillin (1 g twice daily) and esomeprazole (40 mg twice daily). Efficacy of eradication was determined by the (13)C-urea breath test, 6 to 8 weeks after therapy. Compliance and side effects were determined via personal interviews at the end of therapy. Rifabutin toxicity was monitored by analysis of blood samples. RESULTS: H pylori infection was cured in 118 of the patients who received levofloxacin triple therapy (90%; 95% confidence interval, 85%-95%) and 93 of the patients who received rifabutin triple therapy (88.6%; 95% confidence interval, 82%-95%). In each group, the cure rate did not differ significantly between patients infected with H pylori strains resistant to single or multiple antibiotics. Mild side effects occurred in 15.5% and 14.9% of patients resistant to single or multiple antibiotics, respectively, and self-limiting neutropenia was observed in 1 (0.7%) case. CONCLUSIONS: Selection of triple therapy with either levofloxacin or rifabutin, based on results from bacterial culture tests, cures H pylori infection in about 90% who did not previously respond to antibiotics.

The Effects of Two Novel Copper-Based Formulations on Helicobacter pylori.

We investigated the effects of two novel copper-based inorganic formulations for their activity against 60 isolates of Helicobacter pylori (Hp). The two copper-based formulations were tested against three NCTC Helicobacter pylori isolates and 57 clinical strains isolated from the UK and Italy in time-kill assays. Both copper-based formulations were bio-cidal against all Helicobacter pylori strains tested reducing the viable count by 4-5 log within 2 h. These two copper-based anti-microbial agents deserve further study in relation to the treatment of H. pylori-related gastric disease.

High prevalence of primary antibiotic resistance in Helicobacter pylori isolates in Italy.

BACKGROUND AND AIMS: H. pylori eradication with standard therapies is decreasing worldwide, mainly because of increased primary antibiotic resistance rates. We aimed to assess primary resistance in H. pylori isolates towards the most used antibiotics in clinical practice. METHODS: The study enrolled consecutive, dyspeptic, adult patients, never treated for H. pylori, who had underwent upper endoscopy. Gastric biopsies were taken for standard histology, and two further antral biopsies were used for H. pylori culture. Minimal inhibitory concentrations (MIC) >/= 1, >/= 8 and >/= 1 mg/L were used as break point for clarithromycin, metronidazole, and levofloxacin resistance, respectively. RESULTS: Bacterial culture was successful in 145 (94%) out of 154 infected patients. Resistance towards at least one antibiotic was detected in 111 (76.6%) isolated, and multiple antibiotic resistance in 35.2% of cases. Primary resistance towards clarithromycin, metronidazole, and levofloxacin was detected in 51 (35.2%), 86 (59.3%), and in 32 isolated (22.1%), respectively. Levofloxacin resistance was significantly associated with the male sex (OR: 11.3, 95% CI = 1.2-103; P = 0.03), whilst females were at a higher risk of being infected with bacterial strains harbouring a double clarithromycin and metronidazole resistance (OR: 4.9, 95% CI = 1.2-19.8, P = 0.02). CONCLUSION: Our data indicate a very high primary resistance rate towards the most used antibiotics in H. pylori isolates. The efficacy of standard eradication therapies is expected to further decrease in the next years.