Recent studies have shown a noticeable increase in global Helicobacter pylori (H. pylori) resistance, with clarithromycin resistance surpassing 15% in various areas. However, inadequate epidemiological monitoring, especially in developing countries, and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels. The complexity of treating H. pylori is driven by its highly dynamic genome, which is prone to frequent mutations contributing to phenotypical resistance. The usual course of action in empirical treatment involves using a combination of various drugs simultaneously, leading to significant resistance selection pressure and potential side effects. The emergence of H. pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment, highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing, requiring a collection of mixed samples and multiple isolates for accurate assessment. The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors. Additionally, the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.

Background Helicobacter pylori infection has been identified to cause constantly recurring inflammation, leading to gastrointestinal tract disorders, including carcinoma. The standard triple therapy (STT), used to eradicate H. pylori, includes two antimicrobials and a proton pump inhibitor for two weeks. Other drug regimens have also been developed since H. pylori exhibits antimicrobial resistance. These regimens, including probiotics, have been shown to lower adverse drug reactions (ADR), improve drug adherence, exert bacteriostatic effect, and reduce inflammation. Objective This study intended to explore probiotic intervention for improving eradication rates and mitigating adverse effects while administrating STT.  Methods This prospective study was conducted from May to December, 2021, in the Department of Gastroenterology of Ship International Hospital, Dhaka, Bangladesh, to observe the effects of probiotics inclusion along with STT on H. pylori eradication. A total of 100 patients aged ≥18 years who tested positive for H. pylori were included. The experimental group (n=50) was given STT and probiotics, and the control group (n=50) was given only STT without probiotics for 14 days. Necessary follow-up was done six weeks after treatment. An independent sample t-test, chi-square test, and multiple regression analysis were used for statistical analysis. Result The odds of getting rapid urease test (RUT) negative results from positive were 2.06 times higher (95%CI= 0.95, 3.22, p=0.054) in the experimental group. ADRs were crucially towering in the control group (p=0.045) compared to the probiotics group. The probiotics group had a lower risk of having adverse effects by 0.54 times (95%CI=0.19, 0.84, p=0.032) than the control group. Conclusion Using probiotics and STT together to eradicate H. pylori may lower ADR and improve treatment adherence. It may also help terminate H. pylori infection more effectively. More research is required as H. pylori is very contagious and can ultimately cause life-threatening gastric cancer.

Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador.

A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied.

All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%.

In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.

Helicobacter pylori is a pathogenic bacterium associated with various gastrointestinal diseases, including chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The increasing rates of H. pylori antibiotic resistance and the emergence of multidrug-resistant strains pose significant challenges to its treatment. This comprehensive review explores the mechanisms underlying the resistance of H. pylori to commonly used antibiotics and the clinical implications of antibiotic resistance. Additionally, potential strategies for overcoming antibiotic resistance are discussed. These approaches aim to improve the treatment outcomes of H. pylori infections while minimizing the development of antibiotic resistance. The continuous evolution of treatment perspectives and ongoing research in this field are crucial for effectively combating this challenging infection.

Antibiotic resistance of Helicobacter pylori (H. pylori) hampers the success of eradication and in recent years multidrug resistance (MDR) shows an increase worldwide.

This review covers current aspects of pharmacological and regulatory management of MDR-resistant H. pylori infection.

MDR H. pylori is increasing worldwide and its prevalence varies both between continents and countries. High consumption and misuse of antibiotics, H. pylori treatment failures and bacterial factors such as mutations, efflux pumps and biofilms are among the factors associated with MDR. Important steps for confronting the rise of MDR H. pylori strains should follow the principles of antibiotic stewardship, i.e. eradication regimens should be optimized with regard to all aspects of therapy, including drugs, doses, formulation, frequency of administration, administration in relation to meals and duration of therapy that reliably achieve at least 90% (preferably >95%) cure rates in adherent patients with susceptible infections.

Helicobacter pylori (Hp), a well-known human pathogen, causes one of the most common chronic bacterial infections and plays an important role in the emergence of chronic progressive gastric inflammation and a variety of gastrointestinal diseases. The prevalence of Hp infection varies worldwide and is indirectly proportional to socio-economic status, especially during childhood. The response to the eradication therapy significantly depends on the antibiotic resistance specific to each geographical region; thus, currently, given the increasing prevalence of antimicrobial resistance (especially to clarithromycin, metronidazole, and levofloxacin), successful treatment for Hp eradication has become a real challenge and a critical issue. The most incriminated factors associated with multidrug resistance (MDR) in Hp proved to be the overuse or the improper use of antibiotics, poor medication adherence, and bacterial-related factors including efflux pumps, mutations, and biofilms. Up to 30% of first-line therapy fails due to poor patient compliance, high gastric acidity, or high bacteremia levels. Hence, it is of great importance to consider new eradication regimens such as vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, requiring further studies and thorough assessment. Strain susceptibility testing is also necessary for an optimal approach.

Treating Helicobacter pylori infection according to antibiotic resistance has been frequently recommended. However, information on its real effectiveness is scarce.

The aim of this study is to perform a meta-analysis comparing empirical vs. susceptibility-guided treatment of H. pylori.

Selection of studies: Studies comparing empirical versus susceptibility-guided treatment were selected. Search strategy: electronic and manual up to August 2021. Data synthesis: by intention-to-treat (random-effects model).

Overall, 54 studies were included (6,705 patients in the susceptibility-guided group and 7,895 in the empirical group). H. pylori eradication rate was 86 vs. 76%, respectively (RR: 1.12; 95% CI: 1.08-1.17; I 2: 83%). Similar results were found when only RCTs were evaluated (24 studies; RR: 1.16; 95% CI: 1.11-1.22; I 2: 71%) and when susceptibility testing was assessed by culture (RR: 1.12; 95% CI: 1.06-1.18) or PCR (RR: 1.14; 95% CI: 1.05-1.23). For first-line treatments (naïve patients; 30 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR: 1.15; 95% CI: 1.11-1.20; I 2: 79%). However, for empirical first-line quadruple regimens, in particular (both with and without bismuth, excluding the suboptimal triple therapies), not based on CYP2C19 gene polymorphism, no differences in efficacy were found compared with the susceptibility-guided group (RR: 1.04; 95% CI: 0.99-1.09); this lack of difference was confirmed in RCTs (RR: 1.05; 95% CI: 0.99-1.12). For rescue therapies (13 studies, most 2nd-line), similar results were demonstrated for both strategies, including all studies (RR: 1.09; 95% CI: 0.97-1.22; I 2: 82%) and when only RCTs were considered (RR: 1.15; 95% CI: 0.97-1.36).

The benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapies.

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

The detection of Helicobacter pylori mutations that result in antimicrobial resistance can serve as a guideline of antimicrobial therapeutics and probably prevent the failure of clinical treatments. Evaluating the potential of Sanger sequencing to identify genetically resistant determinants in Helicobacter pylori clinical isolates will be important.

180 cultured strains have been tested using agar dilution for antibiotic susceptibility. NCBI BLAST was used to perform genotypic analysis on the sequencing data. Sanger sequencing was evaluated as an alternative method to detect resistant genotypes and susceptibility.

By the conventional E-test, resistance to levofloxacin, amoxicillin, metronidazole, and clarithromycin was 67.3%, 15.1%, 96.4%, and 25.5%, respectively. In contrast, tetracycline had no resistance. Resistance to multiple drugs was observed in 8.12% of the strains. The genetic determinants of resistance to CLA was 23s rRNA, the determinants of resistance to amoxicillin was Pbp1, the determinants of resistance to metronidazole was rdxA, and the determinants of resistance to levofloxacin were GyrA and GyrB. However, there was no association of resistance in tetracycline.

We found increased rates of metronidazole antibiotic resistance, highlighting the necessity for alternative therapies and periodic evaluation. Sanger sequencing has proved to be highly effective and holds the potential to be implemented in policies catering to local treatments.

Helicobacter pylori causes dyspepsia, peptic ulcer, and gastric malignancies. Treatments for Helicobacter pylori are mostly empirical depending on regional antibiotic resistances and the patient's history and less frequently susceptibility guided. Helicobacter pylori has a low resistance to rifabutin and has been proposed as an alternative for third-line treatment and beyond but recently has also gained attention for use as first- and second-line treatment.

In this review, the authors systematically searched medical databases in order to present the current eradication rates for any treatment based on the two antibiotics, rifabutin and amoxicillin with a potent acid inhibitor. They also assessed the safety and tolerance of all the relative regimens.

Treatment with a rifabutin- and amoxicillin-containing regimen is a valuable option when treating difficult to eradicate Helicobacter pylori infections. Its efficacy is overall 71.4%, and it is not influenced by previous antibiotics, gender, smoking habits, and age. Its results were better when used as a first- or second-line treatment. In third-line therapy and beyond, eradication rates are lower. Adverse effects of all rifabutin regimens occurred in 23% of patients and were mostly mild with bone marrow suppression being very low and reversible.

Helicobacter pylori infection may persist after multiple eradication treatments. The aim of this study was to evaluate the efficacy and safety of a furazolidone-based rescue regimen in hyper-refractory patients. A unicentre, prospective study was designed. Patients in whom five or more treatments had consecutively failed were included. All patients had previously received bismuth and key antibiotics, such as amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin, and had positive H. pylori culture, demonstrating resistance to clarithromycin, metronidazole, and levofloxacin. A quadruple regimen with furazolidone (200 mg), amoxicillin (1 g), bismuth (240 mg), and esomeprazole (40 mg) was prescribed twice a day for 14 days. Eradication was confirmed by the stool antigen test. Compliance was determined through questioning, and adverse effects using a questionnaire. Eight patients (mean age 56 years, 63% men, 38% peptic ulcer disease, 12% gastric cancer precursor lesions, and 50% functional dyspepsia) were included. Per-protocol and intention-to-treat eradication rates were 63%. Compliance was 100%. Adverse effects were reported in two (25%) patients, and all were mild. Even after five or more previous H. pylori eradication failures, and a multi-resistant infection, rescue treatment with furazolidone may be effective in approximately two-thirds of the cases, constituting a valid strategy after multiple previous eradication failures with key antibiotics such as clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin.

Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection.

We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs).

Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I²  = 68.1%, P = 0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H. pylori infection (OR 3.78, 95% CI 2.44-5.87, P < 0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P = 0.001) and when daily amoxicillin dose was ≥ 3000 mg or proton pump inhibitor dose was ≥ 80 mg or treatment duration was 14 days (80.6% vs 66.0%, P = 0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I²  = 79.76, P = 0.82).

Evidence for the effectiveness of rifabutin for the first-line treatment of H. pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking.

Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported. Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined. Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23-36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.

Helicobacter pylori infection is associated with chronic gastritis, ulcers and gastric cancer. Antimicrobial resistance has increased worldwide affecting the efficacy of current treatments. Most guidelines recommend implementation of regional surveillance of primary antibiotic resistance of H pylori. Only a fraction of individuals infected with H pylori develop gastric diseases which are related to virulence factors of the bacteria. The aims of the study were to determine the primary antimicrobial resistance rates of H pylori and to know the virulence factors prevalence of strains circulating in Southern Europe.

Susceptibility testing by Etest to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was performed in 102 isolates (99 naïve patients). The prevalence of virulence factors (cagA, vacA, oipA, babA and dupA) was evaluated in 102 H pylori isolates from patients with mild-disease symptoms and in 22 isolates from patients with severe-disease symptoms.

Primary resistance rates were 12.1% to clarithromycin, 13.1% to levofloxacin, 24.2% to metronidazole and 0% to amoxicillin and tetracycline. Combined resistance to clarithromycin and levofloxacin was 3% and to clarithromycin and metronidazole 4%. Prevalence of virulence factors in the mild- and severe-disease group was 35.3% and 81.8% for cagA, 20.6% and 54.5% for cagA/vacAs1m1, 94.1% and 95.4% for babA2, 78.4% and 100% for oipA and 30.4% and 18.2% for dupA.

Primary antimicrobial resistance rates were under 15% for clarithromycin and levofloxacin. The prevalence of H pylori carrying the virulent genotype cagA/vacAs1m1 was higher than 20% in the mild-disease and 54% in the severe-disease symptom group.