Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis‐related gene mutations, rRNA coding gene mutations, and cell wall synthesis‐related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcla.24885

Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice

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.

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

Recent guidelines dictate that all Helicobacter pylori (H. pylori) infected subjects should receive curative therapy. The efficacy of empirical regimens for H. pylori eradication might decline with bacterial, drug, and host factors. The necessity of a tailored therapy still remains controversial. Here we provide a meta‐analysis of the current status of susceptibility‐based (tailored) therapy in which susceptibility‐based therapies were compared to the currently accepted choice of empiric therapy. In this rapidly closing era, neither the susceptibility nor empiric therapies were routinely optimized, such that we report the outcome of comparisons on the efficacy of unoptimized tailored vs. locally preferred empiric treatments.

Current role of tailored therapy in treating Helicobacter pylori infections. A systematic review, meta‐analysis and critical analysis

Patients who have failed two or more attempts to eradicate Helicobacter pylori are commonly referred to as refractory. Although the incidence of refractory Helicobacter pylori infection is only 10–20%, with the increasing rate of antibiotic resistance in various regions, the treatment of refractory Helicobacter pylori infection has gradually become a difficult problem faced by clinicians. When choosing a rescue therapy, the physician must consider numerous factors. A longer treatment duration, higher doses of proton pump inhibitors (PPIs), or the use of potassium-competitive acid blocker (P-CAB) may increase the efficacy of triple therapy or bismuth quadruple therapy. Rescue treatment based on bismuth quadruple therapy usually achieves better results. At the same time, treatment based on drug susceptibility tests or genotypic resistance is recommended where available. Of course, appropriate empiric treatment can also be selected according to local drug resistance, a patient’s previous medication history and compliance. It is the best choice if it can improve the success rate of the first treatment and reduce the occurrence of refractory Helicobacter pylori infection. This review aims to summarize the articles related to refractory Helicobacter pylori in recent years and to explore a better remedial treatment plan for clinicians.

/pdf/treatment-of-refractory-helicobacter-pylori-infection-a-new-1whu464n.pdf

Treatment of refractory Helicobacter pylori infection: A new challenge for clinicians

The article presents information gained from a survey among Norwegian hospitals in March 1997 concerning their treatment of infections with Helicobacter pylori. Altogether 52 hospitals answered the questionnaire. A combination of proton pump inhibitors, metronidazole and clarithromycin was used by 59% as first choice and urea quick test (94%) and urea breath test (42%) as the primary diagnostic procedures, whereas serology was in little use (17%). Besides ordinary ulcer disease, indications for treatment were: ulcer induced by non-steroid anti-inflammatory drugs (79%), gastrooesophageal reflux (37%), non-ulcer dyspepsia (14%) and cancer prophylaxis (14%). The gastro group at the Department of Pharmacotherapeutics at the University of Oslo invited specialists from all health regions to discuss indications for treatment of H pylori, the diagnosis and the role of general practitioners. The extensive use of clarithromycin might be doubtful due to development of resistance. Indications for treatment of H pylori other than ulcer disease and mucosa associated lymphoid tissue lymphoma are still uncertain. Uncritical use of serological tests in primary care should be discouraged. At present there is no uniform strategy for the diagnosis and treatment of H pylori infection, and a coordinated strategy between general practitioners and specialists is needed.

Treatment of Helicobacter pylori infection

After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n = 182) than in the LBQT group (n = 182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P < 0.001) and per protocol (PP) analysis (91.1% vs. 67.8%, P < 0.001). Among patients in the TBQT group with levofloxacin susceptibility, eradication rates were similar in the ALEB (n = 51) and AFEB (n = 50) subgroups according to both the ITT (86.3% vs. 90.0%, P = 0.56) and PP (88.0% vs. 90.0%, P = 0.75) analyses. Isolated clarithromycin and levofloxacin resistance rates were 57.7% and 44.5%, respectively. The total clarithromycin and levofloxacin resistance rate in strains with dual or triple resistance was 35.7%. TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance. Trial registration: Chinese Clinical Trial Registry (
www.chictr.org.cn

): ChiCTR1900027743.

/pdf/efficacy-of-tailored-second-line-therapy-of-helicobacter-10lb0z78pi.pdf

Efficacy of tailored second-line therapy of Helicobacter pylori eradication in patients with clarithromycin-based treatment failure: a multicenter prospective study.

The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.

BACKGROUND AND AIMS
Lugol chromoendoscopy facilitates the endoscopic visualization of esophageal dysplasia and carcinoma. Vitamin C solution (VCS) can theoretically neutralize free iodine, which causes mucosal irritation. The aim was to assess the safety and efficacy of VCS for relieving adverse symptoms caused by Lugol iodine staining.


METHODS
Two hundred forty eligible subjects were randomized to receive 20 mL of normal saline solution (NS), 5% sodium thiosulfate solution (STS), or 2% VCS after spraying 10 mL of 2% Lugol iodine solution on the mid-distal esophagus. The primary endpoints were statistically significant reductions in the acute and late adverse symptom severity scores. The secondary endpoint was the discoloration effect on esophageal brown iodine-stained mucosa.


RESULTS
Spraying both VCS and STS similarly decreased the severity scores of the acute (NS vs VCS = 2.58 vs 1.61, P = 0.040; VCS vs STS = 1.61 vs 1.89, P > 0.999) and late (NS vs VCS = 1.70 vs 0.91, P = 0.002; VCS vs STS = 0.91 vs 1.38; P = 0.212) adverse symptoms after Lugol chromoendoscopy compared with spraying NS. Compared with STS spray, VCS spray remarkably alleviated acute acid regurgitation or heartburn (33% vs 15%, P = 0.017) and late retrosternal discomfort or pain (21% vs 9%, P = 0.027). Moreover, compared with spraying NS, spraying VCS quickly discolored the iodine-stained mucosa, with a better decolorization score (2.26 vs 3.56, P = 0.000), and the effects of fading iodine dye were similar between VCS and STS (3.56 vs 3.59, P = 0.908).


CONCLUSIONS
VCS can reduce the mucosal irritation symptoms induced by Lugol chromoendoscopy and can be routinely recommended.

Iconographies supplémentaires de l'article : The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial

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Efficacy of tailored second-line therapy of Helicobacter pylori eradication in patients with clarithromycin-based treatment failure: a multicenter prospective study.

The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial.

Iconographies supplémentaires de l'article : The safety and efficacy of 2% vitamin C solution spray for relief of mucosal irritation caused by Lugol chromoendoscopy: a multicenter, randomized, double-blind, parallel trial