Clarithromycin-based regimens are commonly used as a first-line therapy for
-positive patients; however, resistance to clarithromycin has led to treatment failures. The aim of this study was to ...evaluate the feasibility of using stool samples to detect the presence of
DNA while concurrently detecting mutations associated with resistance to clarithromycin. For this purpose, total DNA was extracted from 294 raw stool specimens from
-positive and -negative patients. TaqMan real-time PCR amplification was used to detect the presence of
as well as to predict the phenotype of the organism and the related outcome for patients treated with clarithromycin. Clarithromycin resistance was determined upon analysis of the PCR result. Patients were also tested by a urea breath test and were subjected to esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease test, in order to obtain a consensus patient infection status. Of 294 total stool samples, 227 were deemed true positive. The sensitivity of
detection by PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed point mutations associated with clarithromycin resistance (A2142C, A2142G, A2143G). The final correlation of the mutant genotypes as determined by sequencing with the eradication of infection was 86%. We found that
DNA can be detected in human stool specimens with high sensitivity and can therefore be used to determine the presence of the bacterium without obtaining a biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted without obtaining a biopsy sample, facilitating the choice of the right therapeutic approach.
Abstract
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.
Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (e.g. histological examination, culture and rapid urease test) and by non-invasive techniques, ...such as serology, the urea breath test, urine/blood or detection of H. pylori antigen in stool specimen. Some non-invasive tests, such as the urea breath test and the stool antigen test, detect active infection: these are called ‘active tests’. Non-invasive tests (e.g. serology, urine, near-patient tests) are markers of exposure to H. pylori but do not indicate if active infection is ongoing; these are ‘passive tests’. Non-invasive test-and-treat strategies are widely recommended in the primary care setting. The choice of appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness.
Background & Aims Different remission rates of gastric low-grade, B-cell, mucosa–associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the ...long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome. Methods This systematic review analyzed data from 32 studies, including 1408 patients. Results The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3−79.7), and was significantly higher in patients with stage I than stage II1 lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2–MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy. Conclusions H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression.
the increasing prevalence of strains resistant to antimicrobial agents is a critical issue for the management of
infection. This study aimed to evaluate, in Italian naïve patients,
antibiotic ...resistance trends and their potential predictive factors during the last decade.
consecutive Italian naïve
positive patients, referred from General Practitioners to our Unit from January 2009 to January 2019 to perform an upper gastrointestinal endoscopy (UGIE), were considered. Each patient underwent
C-urea breath test (
C-UBT) and UGIE with multiple biopsies to perform rapid urease test (RUT), culture/susceptibility test (vs. clarithromycin, metronidazole, levofloxacin), and histopathological examination.
status was assessed through CRM (composite reference method: at least two tests positive or only culture positive).
between 2009 and 2014, 1763 patients were diagnosed as
positive, 907 were naïve with antibiogram available. Between 2015 and 2019, 1415 patients were diagnosed as
positive, antibiotic susceptibility test was available in 739 naïve patients.
primary antibiotic resistance rates in the first and second five-year period were, respectively, clarithromycin 30.2% (95% CI 27.2-33.3), 37.8% (95% CI 34.2-41.4); metronidazole 33.3% (95% CI 30.2-36.5), 33.6% (95% CI 30.2-37.1); levofloxacin 25.6% (95% CI 22.8-28.5), 33.8% (95% CI 37.4-47.4), double resistance clarithromycin-metronidazole 18.9% (95% CI 16.4-21.6), 20.7% (95% CI 17.8-23.8). The increase of the resistance rates to clarithromycin and levofloxacin in naïve patients was statistically significant (
< 0.05). Although eradication rates for sequential therapy in the 10 years considered were 93.4% (95% CI 92-94.6) and 87.5% (95% CI 85.7-89) at per-protocol (PP) and intention-to-treat (ITT) analysis, respectively, they showed a significant decrease in the second five-year period.
this data highlights an increase in primary
antibiotic resistance and strongly suggests the importance of drug susceptibility testing also in naïve patients.
: Only a few antimicrobials are effective against
, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin ...resistant
as a "high-priority" bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure.
is, in fact, a "fastidious" microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in
. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in
: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole
genome.
: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation.
Background. Antigens derived from Helicobacter pylori can be used as stool biomarkers to assist in the diagnosis of H. pylori infection. Since current assays have variable performance, we assessed ...the clinical performance of the automated LIAISON® Meridian H. pylori SA chemiluminescent immunoassay against more invasive biopsy tests that are considered to be the “gold standard” (Composite Reference Method). Methods. This prospective multisite study enrolled patients undergoing an esophagogastroduodenoscopy with collection of biopsy and stool specimens. Adult patients (≥22 years) participated in the study from February 2017 to August 2018. Specimens of the stomach were tested by three methods, known as the Composite Reference Method: (1) histological evaluation, (2) culture of the organism, and (3) rapid urease detection test. H. pylori in stool was detected using the automated LIAISON® Meridian H. pylori SA assay, a chemiluminescent immunoassay. Statistical analyses were performed using MedCalc 18.11.6. Results. 277 patients (63% female) were included in the study. The prevalence of infected subjects was 24.2% in this study cohort. Clinical performance assessed against the Composite Reference Method showed very good agreement (Cohen’s kappa=0.922), with good sensitivity (95.5%) and specificity (97.6%). Reproducibility study results showed total imprecision ranging from 3.1% to 13.9% CV. Conclusion. The automated LIAISON® Meridian H. pylori SA assay brings reliable noninvasive testing for H. pylori to the laboratory that is in very good agreement with the current, more invasive biopsy-based methods such as histology, culture, or rapid urease test. The clinical trial identifiers are NCT03060746 (pretherapy) and NCT03060733 (posttherapy).
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.
•A decreasing trend in the efficacy of rifabutin-based therapy was detected, particularly when clarithromycin resistance was present.•Our data confirm Pylera® regimen as a reliable option to ...successfully treat eradication failure patients. Indeed, the eradication rates are steadily high (90%) until the fourth-line attempt.•These findings would suggest that the role of rifabutin-based regimen as rescue therapy should be at least reconsidered, and its use reserved to selected patients.•Unfortunately, Pylera® regimen is really complex and causes side-effects more frequently than other therapies.
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.
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.
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.
Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®.
Background
There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a ...three‐in‐one single‐capsule formulation.
Objective
To evaluate the effectiveness and safety of the single‐capsule bismuth quadruple therapy.
Methods
Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention‐to‐treat and per‐protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line.
Results
Finally, 2100 patients were prescribed single‐capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention‐to‐treat effectiveness of 92% was achieved. Eradication was over 90% in first‐line treatment (95% modified intention‐to‐treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention‐to‐treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention‐to‐treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases.
Conclusions
Single‐capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real‐world clinical practice, both as a first‐line and rescue treatment, with good compliance and a favourable safety profile.
Key Summary
The development of a three‐in‐one single‐capsule formulation has led to a resurgence in the use of bismuth quadruple therapy (BQT) to treat Helicobacter pylori infection.
In the largest study carried out to date, the effectiveness of single‐capsule BQT was optimal both as a firstline and as a rescue therapy.
Compliance was the factor most closely associated with treatment effectiveness.
Single‐capsule BQT eradicates H. pylori in approximately 90% of patients in real‐world clinical practice, with a favourable safety profile.
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