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Antibiotics
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Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies
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Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 9148

Special Issue Editors

Prof. Dr. Tomica Milosavljevic

E-Mail Website
Guest Editor
Euromedik Hospital Belgrade, Belgrade, Serbia
Interests: endoscopy; helicobacter infections; gastric cancer
Dr. László Herszényi

E-Mail Website
Guest Editor
2nd Department of Medicine, Semmelweis University, H-1088 Budapest, Hungary
Interests: colorectal cancer; acute; cystocolic fistula; peritoneum lavage

Special Issue Information

Dear Colleagues,

In light of the growing prevalence of Helicobacter pylori (H. pylori), its eradication has been recognized as high priority. Despite efforts to control this pathogen, several factors have hindered its successful eradication. Antibiotic resistance has been recognized as the main driving factor in the treatment failure process.

The indiscriminate use of antibiotics in both clinical and community settings has played a significant role in fueling this problem, selecting for resistant strains and promoting their proliferation. H. pylori has developed an impressive repertoire of resistance mechanisms, rendering traditional antibiotic therapies less effective and highlighting the urgent need for a tailored therapy approach. Repetitive eradication attempts promote further antibiotic resistance, poor patient compliance, and contribute to point mutations while simultaneously weakening host immune systems and potentially leading to yeast co-infection, all of which have been recognized as additional predictors of treatment failure.

The impact of H. pylori antibiotic resistance is multifold, impacting both individual patients and public health. Several mechanisms have been proposed to meet the challenge of eradicating H. pylori, some of which have been implemented in global guidelines and consensus statements.

By fostering an interdisciplinary approach, implementing stringent antibiotic stewardship programs, and promoting tailored treatment approaches, we can strive toward successful H. pylori treatment outcomes.

Prof. Dr. Tomica Milosavljevic
Dr. László Herszényi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Helicobacter pylori
  • eradication therapy
  • antibiotic resistance

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Published Papers (5 papers)

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Research

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10 pages, 1750 KiB  
Article
In Vitro Susceptibility and Synergistic Effect of Bismuth Against Helicobacter pylori
by Jieun Woo, Chang Seok Bang, Jae Jun Lee, Ji Yong Ahn, Jung Mogg Kim, Hwoon-Yong Jung and Eun Jeong Gong
Antibiotics 2024, 13(11), 1004; https://doi.org/10.3390/antibiotics13111004 - 25 Oct 2024
Viewed by 833
Abstract
Background/objectives: Bismuth is commonly used in Helicobacter pylori (H. pylori) eradication therapy. However, few studies have examined the in vitro susceptibility of H. pylori to bismuth. Moreover, the exact mechanism of action of bismuth on H. pylori remains unclear. The aim [...] Read more.
Background/objectives: Bismuth is commonly used in Helicobacter pylori (H. pylori) eradication therapy. However, few studies have examined the in vitro susceptibility of H. pylori to bismuth. Moreover, the exact mechanism of action of bismuth on H. pylori remains unclear. The aim of this study was to identify the anti-bacterial effect of bismuth as well as to evaluate potential synergistic effects between bismuth and various antibiotics. Methods: The minimum inhibitory concentrations (MICs) of three bismuth preparations, bismuth subsalicylate, bismuth potassium citrate, and colloidal bismuth subcitrate (CBS, De-Nol) were determined for H. pylori strains using the agar dilution technique. Agar plates of varying pH values from 5.0 to 8.0 were used to investigate whether acidity influences the anti-bacterial effect of bismuth. A checkerboard assay was performed to assess the synergism between CBS and antibiotics (amoxicillin, clarithromycin, and metronidazole). Results: Twelve H. pylori strains, including three reference strains (H. pylori 26695, J99, and ATCC 43504), and nine clinically isolated strains were tested. The MICs for bismuth subsalicylate, bismuth potassium citrate, and CBS ranged from 4 to 32 μg/mL, 2 to 16 μg/mL, and 1 to 8 μg/mL, respectively. The bismuth MICs for the reference strains were similar at pH 5–8. In the checkerboard assay, no interactions between CBS and any of the antibiotics were observed in the reference H. pylori strains. Conclusions: Bismuth showed in vitro susceptibility against H. pylori. The enhanced eradication efficacy of bismuth-containing regimens appears to be due to mechanisms other than direct synergy with antibiotics. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies)
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11 pages, 1362 KiB  
Article
Genetic Determinants of Clarithromycin and Fluoroquinolones Resistance in Helicobacter pylori in Serbia
by Dusan Kekic, Milos Jovicevic, Jovana Kabic, Iva Lolic, Ina Gajic, Stefan Stojkovic, Lazar Ranin, Tomica Milosavljevic, Natasa Opavski, Ivan Rankovic and Vladimir Milivojevic
Antibiotics 2024, 13(10), 933; https://doi.org/10.3390/antibiotics13100933 - 1 Oct 2024
Viewed by 1053
Abstract
Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for [...] Read more.
Background/Objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations. Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany). Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed. Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies)
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8 pages, 628 KiB  
Article
Point Mutations in Furazolidone and Rifampicin Resistance Genes in Helicobacter pylori Strains from Colombia
by Kevin Andres Guzman, Arsenio Hidalgo and Alvaro Jairo Pazos
Antibiotics 2024, 13(7), 643; https://doi.org/10.3390/antibiotics13070643 - 12 Jul 2024
Viewed by 1331
Abstract
The eradication of Helicobacter pylori is a valid strategy for preventing gastric cancer; however, the therapeutic failure of first-line treatments in Colombia is associated with high resistance to metronidazole and amoxicillin. This study explored alternative antibiotics and analyzed point mutations in resistance genes [...] Read more.
The eradication of Helicobacter pylori is a valid strategy for preventing gastric cancer; however, the therapeutic failure of first-line treatments in Colombia is associated with high resistance to metronidazole and amoxicillin. This study explored alternative antibiotics and analyzed point mutations in resistance genes to furazolidone and rifampicin in order to include them in rescue therapy regimens. A total of 239 complete genomes of Helicobacter pylori Colombian strains were compared to that of the ATCC 26695 strain to identify mutations in the rpoB and porD genes for rifampicin and furazolidinone resistance, respectively. While rifampicin resistance mutations were not found, only 0.84% of the isolates showed the porD gene, suggesting that Helicobacter pylori is sensitive to these antibiotics. A phylogenomic analysis of Helicobacter pylori revealed an independent lineage in Colombia (hspColombia). The absence of point mutations in the rpoB gene, together with the scarce mutations identified in the porD gene of Helicobacter pylori, suggest that the hspColombia isolates are sensitive to rifampicin and furazolidone, which could be key to including these antibiotics in the rescue therapies against Helicobacter pylori. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies)
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11 pages, 688 KiB  
Article
Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant Helicobacter pylori
by Meltem Ayaş, Sinem Oktem-Okullu, Orhan Özcan, Tanıl Kocagöz and Yeşim Gürol
Antibiotics 2024, 13(5), 396; https://doi.org/10.3390/antibiotics13050396 - 26 Apr 2024
Cited by 2 | Viewed by 1717
Abstract
Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of Helicobacter pylori infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in H. pylori are associated with point mutations in 23S ribosomal RNA (rRNA), the [...] Read more.
Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of Helicobacter pylori infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in H. pylori are associated with point mutations in 23S ribosomal RNA (rRNA), the relationships of other mutations with resistance remain unclear. We examined possible new macrolide resistance mechanisms in resistant strains using next-generation sequencing. Two resistant strains were obtained from clarithromycin-susceptible H. pylori following exposure to low clarithromycin concentrations using the agar dilution method. Sanger sequencing and whole-genome sequencing were performed to detect resistance-related mutations. Both strains carried the A2142G mutation in 23S rRNA. Candidate mutations (T1495A, T1494A, T1490A, T1476A, and G1472T) for clarithromycin resistance were detected in the Mutant-1 strain. Furthermore, a novel mutation in the gene encoding for the sulfite exporter TauE/SafE family protein was considered to be linked to clarithromycin resistance or cross-resistance, being identified as a target for further investigations. In the Mutant-2 strain, a novel mutation in the gene that encodes DUF874 family protein that can be considered as relevant with antibiotic resistance was detected. These mutations were revealed in the H. pylori genome for the first time, emphasizing their potential as targets for advanced studies. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies)
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Review

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36 pages, 7783 KiB  
Review
Sequential versus Standard Triple Therapy for First-Line Helicobacter pylori Eradication: An Update
by Olga P. Nyssen, Belén Martínez, Francis Mégraud, Vincenzo Savarino, Carlo A. Fallone, Franco Bazzoli and Javier P. Gisbert
Antibiotics 2024, 13(2), 136; https://doi.org/10.3390/antibiotics13020136 - 30 Jan 2024
Cited by 3 | Viewed by 3065
Abstract
Background: non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-Helicobacter pylori treatment alternative to standard triple therapy (STT). Methods: We conducted a systematic review with a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of 10-day SEQ vs. STT (of [...] Read more.
Background: non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-Helicobacter pylori treatment alternative to standard triple therapy (STT). Methods: 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. Results: 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; p < 0.001). The results were highly heterogeneous (I2 = 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. Conclusions: 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 H. pylori treatment. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection and Antibiotic Resistance: The Emerging Eradication Strategies)
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