Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Impact of a clinical pathway on treatment outcome in patients with acute pancreatitis.

AIM: To determine the impact of a clinical pathway (CP) on acute pancreatitis (AP) treatment outcome. METHODS: A retrospective analysis of medical records was performed. We compared the results of AP treatment outcome over two time periods in our centre, before (2006-2007) and after (2010-2012) the implementation of a CP. The CP comprised the following indicators of quality: performance of all laboratory tests on admission (including lipids and carbohydrate deficient transferrin), determination of AP aetiology, abdomen ultrasound (US) within the first 24 h after admission, contrast-enhanced computed tomography of the abdomen in all cases of suspected pancreatic necrosis, appropriately selected and sufficiently used antibiotic therapy (if necessary), pain control, adequate hydration, control of haemodynamic parameters and transfer to the Intensive Care Unit (ICU) (if necessary), endoscopic retrograde cholangiopancreatography (ERCP) in biliary AP, surgical treatment (if necessary), and advice on outpatient follow-up after discharge. A comparison of the length of stay with that in other Slovenian hospitals was also performed. RESULTS: There were 139 patients treated in the three-year period after the introduction of a CP, of which 81 (58.3%) were male and 58 (41.7%) female. The patients' mean age was 59.6 ± 17.3 years. The most common aetiologies were alcoholism and gallstones (38.8% each), followed by unexplained (11.5%), drug-induced, hypertriglyceridemia, post ERCP (2.9% each) and tumours (2.2%). Antibiotic therapy was prescribed in 72 (51.8%) patients. Abdominal US was performed in all patients within the first 24 h after admission. Thirty-two (23.0%) patients were treated in the ICU. Four patients died (2.9%). In comparison to 2006-2007, we found an increased number of alcoholic and biliary AP and an associated decrease in the number of unexplained aetiology cases. The use of antibiotics also significantly decreased after the implementation of a CP (from 70.3% to 51.8%; P = 0.003). There was no statistically significant difference in mortality (1.8% vs 2.9%). The length of stay was significantly shorter when compared to the Slovenian average (P = 0.018). CONCLUSION: The introduction of a CP has improved the treatment of patients with AP, as assessed by all of the observed parameters.

Multi locus sequence typing (MLST) used as a tool to confirm the ability of susceptible Helicobacter pylori strains to gain resistance to clarithromycin during eradication therapy.

BACKGROUND/AIMS: Primary resistance of H. pylori to clarithromycin is the most common reason for eradication failure, followed by mixed susceptible/ resistant H. pylori strain infection. To distinguish between mixed infections and H. pylori switch to resistance phenotype during eradication therapy, we proceeded with multi locus sequence typing (MLST) of H. pylori strains isolated from gastric biopsy samples of patients before and after eradication therapy. METHODOLOGY: We collected H. pylori isolates from gastric biopsies from 133 patients who were never treated for H. pylori. Five patients had eradication failure with the first isolate susceptible and second isolate resistant to clarithromycin. To analyse genotypes of first and second H. pylori isolates, we compared H. pylori strain sequences of 7 housekeeping genes with MLST. RESULTS: Five patients had clarithromycin-sensitive H. pylori before eradication therapy and gained H. pylori-resistant to clarithromycin after eradication therapy. The sensitive and resistant colonies of each of the H. pylori populations, taken from patients before/after antibiotic therapy, had identical sequence types (ST) obtained with MLST. CONCLUSIONS: The factors favouring H. pylori survival and switch to antibiotic-resistance during eradication therapy probably enable milder environmental conditions for H. pylori persistence during therapy. One of such factor is the ineffective destruction of mucosa-adhered H. pylori by immune cells during therapy which may be due to locally induced immune deficit by H. pylori molecules like strain specific H. pylori lipopolysaccharides.