Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert ...groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth quadruple therapy for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts. The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.
Abstract Background & aims Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to review the literature and provide specific, updated ...recommendations for eradication therapy in adults. Methods A systematic literature search identified studies on H. pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. Results Because of increasing failure of therapy, the consensus group strongly recommended that all H. pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant non-bismuth quadruple therapy (proton pump inhibitor, PPI + amoxicillin + metronidazole + clarithromycin, PAMC), and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBMT). PPI triple therapy (PPI + clarithromycin and either amoxicillin or metronidazole) was restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin, PAL). Rifabutin regimens should be restricted to patients who fail at least 3 prior options. Conclusions Optimal treatment of H. pylori requires careful attention to local antibiotic resistance and eradication patterns. Quadruple therapies PAMC or PBMT should play a more prominent role in H. pylori eradication and all treatments should be given for 14 days.
INTRODUCTION
Our population‐based study assessed whether clinically apparent Helicobacter pylori infection (CAHPI) is associated with the risk of Alzheimer's disease (AD).
METHODS
We assembled a ...population‐based cohort of all dementia‐free subjects in the United Kingdom's Clinical Practice Research Datalink (UK CPRD), aged ≥50 years (1988–2017). Using a nested case‐control approach, we matched each newly developed case of AD with 40 controls. Conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with CAHPI compared with no CAHPI during ≥2 years before the index date. We also used salmonellosis as a negative control exposure.
RESULTS
Among 4,262,092 dementia‐free subjects, 40,455 developed AD after a mean 11 years of follow‐up. CAHPI was associated with an increased risk of AD (OR, 1.11; 95% CI, 1.01–1.21) compared with no CAHPI. Salmonellosis was not associated with the risk of AD (OR, 1.03; 95% CI, 0.82–1.29).
DISCUSSION
CAHPI was associated with a moderately increased risk of AD.
Highlights
CAHPI was associated with an 11% increased risk of AD in subjects aged ≥50 years.
The increase in the risk of AD reached a peak of 24% a decade after CAHPI onset.
There was no major effect modification by age or sex.
Sensitivity analyses addressing several potential biases led to consistent results.
Background
Non‐bismuth quadruple sequential therapy (SEQ) comprising a first induction phase with a dual regimen of amoxicillin and a proton pump inhibitor (PPI) for five days followed by a triple ...regimen phase with a PPI, clarithromycin and metronidazole for another five days, has been suggested as a new first‐line treatment option to replace the standard triple therapy (STT) comprising a proton pump inhibitor (PPI), clarithromycin and amoxicillin, in which eradication proportions have declined to disappointing levels.
Objectives
To conduct a meta‐analysis of randomised controlled trials (RCTs) comparing the efficacy of a SEQ regimen with STT for the eradication of H. pylori infection, and to compare the incidence of adverse effects associated with both STT and SEQ H. pylori eradication therapies.
Search methods
We conducted bibliographical searches in electronic databases, and handsearched s from Congresses up to April 2015.
Selection criteria
We sought randomised controlled trials (RCTs) comparing 10‐day SEQ and STT (of at least seven days) for the eradication of H. pylori. Participants were adults and children diagnosed as positive for H. pylori infection and naïve to H. pylori treatment.
Data collection and analysis
We used a pre‐piloted, tabular summary to collect demographic and medical information of included study participants as well as therapeutic data and information related to the diagnosis and confirmatory tests.
We evaluated the difference in intention‐to‐treat eradication between SEQ and STT regimens across studies, and assessed sources of the heterogeneity of this risk difference (RD) using subgroup analyses.
We evaluated the quality of the evidence following Cochrane standards, and summarised it using GRADE methodology.
Main results
We included 44 RCTs with a total of 12,284 participants (6042 in SEQ and 6242 in STT). The overall analysis showed that SEQ was significantly more effective than STT (82% vs 75% in the intention‐to‐treat analysis; RD 0.09, 95% confidence interval (CI) 0.06 to 0.11; P < 0.001, moderate‐quality evidence). Results were highly heterogeneous (I² = 75%), and 20 studies did not demonstrate differences between therapies.
Reporting by geographic region (RD 0.09, 95% CI 0.06 to 0.12; studies = 44; I² = 75%, based on low‐quality evidence) showed that differences between SEQ and STT were greater in Europe (RD 0.16, 95% CI 0.14 to 0.19) when compared to Asia, Africa or South America. European studies also showed a tendency towards better efficacy with SEQ; however, this tendency was reversed in 33% of the Asian studies. Africa reported the closest risk difference (RD 0.14 , 95% 0.07 to 0.22) to Europe among studied regions, but confidence intervals were wider and therefore the quality of the evidence showing SEQ to be superior to STT was reduced for this region.
Based on high‐quality evidence, subgroup analyses showed that SEQ and STT therapies were equivalent when STT lasted for 14 days. Although, overall, the mean eradication proportion with SEQ was over 80%, we noted a tendency towards a lower average effect with this regimen in the more recent studies (2008 and after); weighted linear regression showed that the efficacies of both regimens evolved differently over the years, having a higher reduction in the efficacy of SEQ (‐1.72% yearly) than in STT (‐0.9% yearly). In these more recent studies (2008 and after) we were also unable to detect the superiority of SEQ over STT when STT was given for 10 days.
Based on very low‐quality evidence, subgroup analyses on antibiotic resistance showed that the widest difference in efficacy between SEQ and STT was in the subgroup analysis based on clarithromycin‐resistant participants, in which SEQ reached a 75% average efficacy versus 43% with STT.
Reporting on adverse events (AEs) (RD 0.00, 95% CI ‐0.02 to 0.02; participants = 8103; studies = 27; I² = 26%, based on high‐quality evidence) showed no significant differences between SEQ and STT (20.4% vs 19.5%, respectively) and results were homogeneous.
The quality of the studies was limited due to a lack of systematic reporting of the factors affecting risk of bias. Although randomisation was reported, its methodology (e.g. algorithms, number of blocks) was not specified in several studies. Additionally, the other 'Risk of bias' domains (such as allocation concealment of the sequence randomisation, or blinding during either performance or outcome assessment) were also unreported.
However, subgroup analyses as well as sensitivity analyses or funnel plots indicated that treatment outcomes were not influenced by the quality of the included studies. On the other hand, we rated 'length of STT' and AEs for the main outcome as high‐quality according to GRADE classification; but we downgraded 'publication date' quality to moderate, and 'geographic region' and 'antibiotic resistance' to low‐ and very low‐quality, respectively.
Authors' conclusions
Our meta‐analysis indicates that prior to 2008 SEQ was more effective than STT, especially when STT was given for only seven days. Nevertheless, the apparent advantage of sequential treatment has decreased over time, and more recent studies do not show SEQ to have a higher efficacy versus STT when STT is given for 10 days.
Based on the results of this meta‐analysis, although SEQ offers an advantage when compared with STT, it cannot be presented as a valid alternative, given that neither SEQ nor STT regimens achieved optimal efficacy ( ≥ 90% eradication rate).
The preparation for colonoscopy is elaborate and complex. In the context of colorectal cancer screening, up to 11% of patients do not keep their colonoscopy appointments and up to 33% of those ...attending their appointments have inadequately cleansed bowels that can delay cancer diagnosis and treatment. A smartphone app may be an acceptable and wide-reaching tool to improve patient adherence to colonoscopy.
The aim of this qualitative study was to employ a user-centered approach to design the content and features of a smartphone app called colonAPPscopy to support individuals preparing for their colonoscopy appointments.
We conducted 2 focus group discussions (FGDs) with gastroenterology patients treated at the McGill University Health Centre in Montreal, Canada. Patients were aged 50 to 75 years, were English- or French-speaking, and had undergone outpatient colonoscopy in the previous 3 months; they did not have inflammatory bowel disease or colorectal cancer. FGDs were 75 to 90 min, conducted by a trained facilitator, and audiotaped. Participants discussed the electronic health support tools they might use to help them prepare for the colonoscopy, the content needed for colonoscopy preparation, and the features that would make the smartphone app useful. Recordings of FGDs were transcribed and analyzed using thematic analysis to identify key user-defined content and features to inform the design of colonAPPscopy.
A total of 9 patients (7 male and 2 female) participated in one of 2 FGDs. Main content areas focused on bowel preparation instructions, medication restrictions, appointment logistics, communication, and postcolonoscopy expectations. Design features to make the app useful and engaging included minimization of data input, reminders and alerts for up to 7 days precolonoscopy, and visual aids. Participants wanted a smartphone app that comes from a trusted source, sends timely and tailored messages, provides reassurance, provides clear instructions, and is simple to use.
Participants identified the need for postcolonoscopy information as well as reminders and alerts in the week before colonoscopy, novel content, and features that had not been included in previous smartphone-based strategies for colonoscopy preparation. The ability to tailor instructions made the smartphone app preferable to other modes of delivery. Study findings recognize the importance of including potential users in the development phase of building a smartphone app.
Aim. There is a paucity of data on the efficacy of empiric H. pylori treatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a ...second through sixth line treatment. Methods. In this single gastroenterology center prospective study in Montreal, Canada, patients with failed H. pylori treatment were offered empiric salvage therapy based on the patients’ previous antibiotic exposure. Enrollment occurred after 1–5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment. Results. 205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13–37), ITT = 62% (49/79), ARR: 22% (95% CI: 10–35), and p < 0.001 ) and when compared to levofloxacin triple therapy (PP = 66% (40/61), ARR: 26% (95% CI: 13–39), ITT = 61% (40/66), and ARR: 24% (95% CI: 10–37)). Eradication was achieved in a high proportion with BQT on attempt two (PP = 94% (67/71), ITT = 91% (67/74)), three (PP = 85% (17/20), ITT = 71% (17/24)), four (PP = 100% (11/11), ITT = 92% (11/12)), and five (PP = 86% (6/7), ITT = 75% (6/8)). Patients with previous combined bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11–64), and p < 0.001 ; ITT: 55% (6/11) versus 90% (94/105), ARR: 35% (95% CI: 10–62), and p < 0.01 ). Conclusions. Salvage therapy with a bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.
Successful Helicobacter pylori eradication with the traditional seven-day course of proton pump inhibitor (PPI) triple therapy is declining. Prolonging therapy to either 10 or 14 days is associated ...with better eradications rates.
To compare the effectiveness of 14-day course of triple therapy versus a 10-day course in the treatment of H pylori in Canada.
Consecutive treatment-naive patients with clinical indications for H pylori eradication underwent either a 10-day course or a 14-day course of traditional PPI triple therapy depending on the date of the office visit (an odd date received the 10-day course, whereas an even date received the 14-day treatment). H pylori eradication was ascertained via urea breath test or gastric biopsies performed ≥4 weeks after completion of therapy. Analyses were by both intention to treat and per-protocol.
A total of 83 patients were included in the study (31 in the 10-day group and 52 in the 14-day group). In the intention-to-treat analysis, eradication rates were 82.7% (95% CI 70% to 92%) versus 45.2% (95% CI 27% to 64%), favouring the 14-day treatment (P<0.001). Similarly, in the per-protocol analysis, eradication rates were 91.5% (95% CI 80% to 98%) versus 63.6% (95% CI 41% to 83%), favouring the 14-day arm (P=0.01). Adverse events and compliance were not significantly different between the two groups.
A 14-day course of standard PPI triple therapy was superior to a shorter-duration therapy and should be included as a first-line regimen for H pylori eradication in Canada. The 10-day course of treatment did not achieve an acceptable eradication rate and should no longer be used in this country.
Helicobacter pylori Infection Graham, David Y; Dang, Bich N; El-Serag, Hashem B ...
The New England journal of medicine,
08/2019, Letnik:
381, Številka:
6
Journal Article
Recenzirano
To the Editor:
In the Clinical Practice article on the treatment of
Helicobacter pylori
infection (March 21 issue),
1
Crowe seems to be ignoring the principles of antimicrobial stewardship, and many ...of the recommendations are based largely on meta-analyses of studies of resistant infections that generally report poor results.
2
The American College of Gastroenterology (ACG) Clinical Guideline, the Toronto Consensus, and the Maastricht V/Florence Consensus Report also recommend concomitant therapy (with a proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole), in which each patient receives at least one unnecessary antibiotic. Such recommendations result in the administration of more than 14,000 kg of . . .
non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-
treatment alternative to standard triple therapy (STT).
We conducted a systematic review with a meta-analysis of randomized ...controlled trials (RCTs) comparing the efficacy of 10-day SEQ vs. STT (of at least 7 days) using bibliographical searches up to July 2021, including treatment-naïve adult or children. The intention-to-treat (ITT) eradication rate and the risk difference (RD) were calculated.
Overall, 69 RCTs were evaluated, including 19,657 patients (9486 in SEQ; 10,171 in STT). Overall, SEQ was significantly more effective than STT (82% vs. 75%; RD 0.08;
< 0.001). The results were highly heterogeneous (
= 68%), and 38 studies did not demonstrate differences between therapies. Subgroup analyses suggested that patients with clarithromycin resistance only and all geographical areas but South America could benefit more from SEQ. Both therapies have evolved over the years, showing similar results when STT lasted 14 days; however, a tendency toward lower SEQ efficacy was noted from 2010 onwards.
Prior to 2010, SEQ was significantly more effective than STT, notably when 7-day STT was prescribed. A tendency toward lower differences between SEQ and STT has been noted, especially when using 10-day STT. None of the therapies achieved an optimal efficacy and therefore cannot be recommended as a valid first-line
treatment.
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