Editorial

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5 pages, 189 KiB

Open AccessEditorial

Antibiotic Resistance and Therapy for Helicobacter pylori Infection

by Stella I. Smith and Yoshio Yamaoka

Antibiotics 2023, 12(12), 1669; https://doi.org/10.3390/antibiotics12121669 - 28 Nov 2023

Cited by 2 | Viewed by 1044

Abstract

Approximately half of the world’s population is estimated to be infected with Helicobacter pylori [...] Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

Research

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33 pages, 4558 KiB

Open AccessArticle

Global Antimicrobial Resistance Gene Study of Helicobacter pylori: Comparison of Detection Tools, ARG and Efflux Pump Gene Analysis, Worldwide Epidemiological Distribution, and Information Related to the Antimicrobial-Resistant Phenotype

by Ricky Indra Alfaray, Batsaikhan Saruuljavkhlan, Kartika Afrida Fauzia, Roberto C. Torres, Kaisa Thorell, Selva Rosyta Dewi, Kirill A. Kryukov, Takashi Matsumoto, Junko Akada, Ratha-korn Vilaichone, Muhammad Miftahussurur and Yoshio Yamaoka

Antibiotics 2023, 12(7), 1118; https://doi.org/10.3390/antibiotics12071118 - 28 Jun 2023

Cited by 1 | Viewed by 1969

Abstract

We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then [...] Read more.

We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the ‘Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)’, while ARG-ACC—the ARG in the accessory genome—are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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12 pages, 1760 KiB

Open AccessArticle

by Kartika Afrida Fauzia, Hafeza Aftab, Evariste Tshibangu-Kabamba, Ricky Indra Alfaray, Batsaikhan Saruuljavkhlan, Alain Cimuanga-Mukanya, Takashi Matsumoto, Phawinee Subsomwong, Junko Akada, Muhammad Miftahussurur and Yoshio Yamaoka

Antibiotics 2023, 12(2), 279; https://doi.org/10.3390/antibiotics12020279 - 31 Jan 2023

Cited by 11 | Viewed by 2180

Abstract

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, [...] Read more.

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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11 pages, 1885 KiB

Open AccessArticle

A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori

by Abdolhakim Mohamed, John N Chilingerian, Prerna Bali, Marygorret Obonyo and Anjan Debnath

Antibiotics 2022, 11(11), 1605; https://doi.org/10.3390/antibiotics11111605 - 11 Nov 2022

Cited by 2 | Viewed by 1468

Abstract

Helicobacter pylori is responsible for a wide range of gastric diseases, including gastric cancer and gastritis. With half of the world’s population infected by H. pylori and the current standard of care associated with suboptimal outcomes, a search for more effective drugs is [...] Read more.

Helicobacter pylori is responsible for a wide range of gastric diseases, including gastric cancer and gastritis. With half of the world’s population infected by H. pylori and the current standard of care associated with suboptimal outcomes, a search for more effective drugs is critical. To facilitate drug screening for H. pylori, we developed a microtiter plate-based compound screening method that is faster and can screen multiple compounds. We identified activities of fexinidazole and its sulfoxide and sulfone metabolites against H. pylori. Both fexinidazole and its metabolites exhibited equipotency against SS1, 60190, and G27 strains, which were about 3–6-fold more potent than the currently used metronidazole. We also determined the minimal inhibitory concentration (MIC) of metronidazole, fexinidazole, and its metabolites against these strains by a traditional agar plate-based method. While MIC values of fexinidazole and metronidazole were similar against all the strains, both sulfoxide and sulfone showed lower MIC values than metronidazole against SS1 and 60190. Given the recent FDA approval of fexinidazole, our data on the in vitro antibacterial activities of fexinidazole and its metabolites support further evaluation of this drug with the goal of producing an alternative nitro-based antimicrobial with good safety profiles for the treatment of H. pylori infection. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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Review

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14 pages, 392 KiB

Open AccessReview

The Influence of Helicobacter pylori on Human Gastric and Gut Microbiota

by Marcello Fiorani, Ege Tohumcu, Livio Enrico Del Vecchio, Serena Porcari, Giovanni Cammarota, Antonio Gasbarrini and Gianluca Ianiro

Antibiotics 2023, 12(4), 765; https://doi.org/10.3390/antibiotics12040765 - 16 Apr 2023

Cited by 9 | Viewed by 3654

Abstract

Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected [...] Read more.

Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected by H. pylori colonization, with consequent effects on the gastrointestinal microbiota, exerted via the regulation of various factors, including gastric acidity, host immune responses, antimicrobial peptides, and virulence factors. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Notably, therapy regimens integrated with probiotics have been shown to reduce the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient’s compliance. In light of the deep impact of gut microbiota alterations on human health, the present article aims to provide an overview of the complex interaction between H. pylori and the gastrointestinal microbiota, focusing also on the consequences of eradication therapies and the effects of probiotic supplementation. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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19 pages, 358 KiB

Open AccessReview

Treatment of Helicobacter pylori Infection in Patients with Penicillin Allergy

by Ligang Liu and Milap C. Nahata

Antibiotics 2023, 12(4), 737; https://doi.org/10.3390/antibiotics12040737 - 10 Apr 2023

Cited by 2 | Viewed by 3290

Abstract

Helicobacter pylori is among the prevalent causes of infections worldwide, and its resistance rate to antibiotics has been rising over time. Amoxicillin is the cornerstone for the treatment regimen. However, the prevalence of penicillin allergy ranges from 4% to 15%. In patients with [...] Read more.

Helicobacter pylori is among the prevalent causes of infections worldwide, and its resistance rate to antibiotics has been rising over time. Amoxicillin is the cornerstone for the treatment regimen. However, the prevalence of penicillin allergy ranges from 4% to 15%. In patients with true allergy, Vonoprazan-Clarithromycin-Metronidazole and bismuth quadruple therapy have demonstrated excellent eradication and high adherence rates. Vonoprazan-based therapy is administered less frequently and may be better tolerated than bismuth quadruple therapy. Therefore, vonoprazan-based therapy may be considered as a first-line therapy if accessible. Bismuth quadruple therapy can be used as the initial therapy when vonoprazan is unavailable. Levofloxacin or sitafloxacin-based regimens achieve a moderately high eradication rate. However, these are associated with potentially serious adverse effects and should only be used when other effective and safer regimens are unavailable. Cephalosporins such as cefuroxime have been used as an alternative to amoxicillin. Microbial susceptibility studies can guide the selection of appropriate antibiotics. PPI-Clarithromycin-Metronidazole fails to achieve a high eradication rate and should be used as a second-line therapy. PPI-Clarithromycin-Rifabutin should not be used because of low eradication rate and frequent adverse reactions. The choice of the most effective antibiotic regimen can enhance clinical outcomes in patients with H. pylori infection and penicillin allergy. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

15 pages, 926 KiB

Open AccessReview

Recombinant Helicobacter pylori Vaccine Delivery Vehicle: A Promising Tool to Treat Infections and Combat Antimicrobial Resistance

by Yakhya Dieye, Cheikh Momar Nguer, Fatou Thiam, Abou Abdallah Malick Diouara and Cheikh Fall

Antibiotics 2022, 11(12), 1701; https://doi.org/10.3390/antibiotics11121701 - 25 Nov 2022

Cited by 4 | Viewed by 1841

Abstract

Antimicrobial resistance (AMR) has become a global public health threat. Experts agree that unless proper actions are taken, the number of deaths due to AMR will increase. Many strategies are being pursued to tackle AMR, one of the most important being the development [...] Read more.

Antimicrobial resistance (AMR) has become a global public health threat. Experts agree that unless proper actions are taken, the number of deaths due to AMR will increase. Many strategies are being pursued to tackle AMR, one of the most important being the development of efficient vaccines. Similar to other bacterial pathogens, AMR in Helicobacter pylori (Hp) is rising worldwide. Hp infects half of the human population and its prevalence ranges from <10% in developed countries to up to 90% in low-income countries. Currently, there is no vaccine available for Hp. This review provides a brief summary of the use of antibiotic-based treatment for Hp infection and its related AMR problems together with a brief description of the status of vaccine development for Hp. It is mainly dedicated to genetic tools and strategies that can be used to develop an oral recombinant Hp vaccine delivery platform that is (i) completely attenuated, (ii) can survive, synthesize in situ and deliver antigens, DNA vaccines, and adjuvants to antigen-presenting cells at the gastric mucosa, and (iii) possibly activate desired compartments of the gut-associated mucosal immune system. Recombinant Hp vaccine delivery vehicles can be used for therapeutic or prophylactic vaccination for Hp and other microbial pathogens. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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11 pages, 586 KiB

Open AccessReview

Clinical Implication of Drug Resistance for H. pylori Management

by Erick A. Argueta, Jonathan J. C. Ho, Yousef Elfanagely, Erika D’Agata and Steven F. Moss

Antibiotics 2022, 11(12), 1684; https://doi.org/10.3390/antibiotics11121684 - 23 Nov 2022

Cited by 7 | Viewed by 1818

Abstract

Rates of antimicrobial-resistance among H. pylori strains are increasing worldwide, resulting in declining eradication rates with current therapies, especially those containing clarithromycin or levofloxacin. To improve H. pylori management, a paradigm shift is needed, from the empiric approaches formerly employed, to regimen selection [...] Read more.

Rates of antimicrobial-resistance among H. pylori strains are increasing worldwide, resulting in declining eradication rates with current therapies, especially those containing clarithromycin or levofloxacin. To improve H. pylori management, a paradigm shift is needed, from the empiric approaches formerly employed, to regimen selection based upon knowledge of local and patient-level antimicrobial susceptibility data. We review the mechanisms of H. pylori antimicrobial resistance and the available worldwide pattern of resistance to key antimicrobials used in H. pylori therapy. The practicalities and challenges of measuring susceptibility in clinical practice is discussed, including not only conventional culture-based techniques but also novel sequencing-based methods performed on gastric tissue and stool samples. Though clinical trials of “tailored” (susceptibility-based) treatments have yet to show the clear superiority of tailored over empiric regimen selection, the ability to measure and modify treatment based upon antimicrobial susceptibility testing is likely to become more frequent in clinical practice and should lead to improved H. pylori management in the near future. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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27 pages, 2030 KiB

Open AccessReview

Clinical Implications of Helicobacter pylori Antibiotic Resistance in Italy: A Review of the Literature

by Enrico Celestino Nista, Antonio Pellegrino, Lucia Giuli, Marcello Candelli, Tommaso Schepis, Sara Sofia De Lucia, Veronica Ojetti, Francesco Franceschi and Antonio Gasbarrini

Antibiotics 2022, 11(10), 1452; https://doi.org/10.3390/antibiotics11101452 - 21 Oct 2022

Cited by 5 | Viewed by 2301

Abstract

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a “high priority” pathogen in 2017. As international guidelines recommend empirical therapy [...] Read more.

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a “high priority” pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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14 pages, 520 KiB

Open AccessReview

Antimicrobial Resistance Profile by Metagenomic and Metatranscriptomic Approach in Clinical Practice: Opportunity and Challenge

by Langgeng Agung Waskito, Yudith Annisa Ayu Rezkitha, Ratha-korn Vilaichone, I Dewa Nyoman Wibawa, Syifa Mustika, Titong Sugihartono and Muhammad Miftahussurur

Antibiotics 2022, 11(5), 654; https://doi.org/10.3390/antibiotics11050654 - 13 May 2022

Cited by 6 | Viewed by 3123

Abstract

The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause [...] Read more.

The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause policy makers to adjust their policies. Current widely performed procedures for the identification of antibiotic-resistant bacteria rely on culture-based methodology. However, some resistance determinants, such as free-floating DNA of resistance genes, are outside the bacterial genome, which could be potentially transferred under antibiotic exposure. Metagenomic and metatranscriptomic approaches to profiling antibiotic resistance offer several advantages to overcome the limitations of the culture-based approach. These methodologies enhance the probability of detecting resistance determinant genes inside and outside the bacterial genome and novel resistance genes yet pose inherent challenges in availability, validity, expert usability, and cost. Despite these challenges, such molecular-based and bioinformatics technologies offer an exquisite advantage in improving clinicians’ diagnoses and the management of resistant infectious diseases in humans. This review provides a comprehensive overview of next-generation sequencing technologies, metagenomics, and metatranscriptomics in assessing antimicrobial resistance profiles. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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Other

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8 pages, 438 KiB

Open AccessPerspective

Helicobacter pylori Infection: Antibiotic Resistance and Solutions for Effective Management in Africa

by Mashiko Setshedi and Stella I. Smith

Antibiotics 2023, 12(6), 969; https://doi.org/10.3390/antibiotics12060969 - 26 May 2023

Cited by 2 | Viewed by 1285

Abstract

Helicobacter pylori (H. pylori) infection is ubiquitous worldwide, with prevalence rates of greater than 70% in Africa. Symptomatic patients present with foregut gastrointestinal symptoms which can be readily diagnosed with standardized non-invasive or invasive tests. The biggest challenge, however, is in [...] Read more.

Helicobacter pylori (H. pylori) infection is ubiquitous worldwide, with prevalence rates of greater than 70% in Africa. Symptomatic patients present with foregut gastrointestinal symptoms which can be readily diagnosed with standardized non-invasive or invasive tests. The biggest challenge, however, is in the management of this condition with rising antimicrobial resistance rates to most of the antibiotics recommended for therapy. This is a problem worldwide, but more specifically in Africa, where the socio-economic and political climate is such that eradication of this organism seems impossible. Furthermore, the recommended antimicrobial susceptibility testing for drug resistance is not widely available in Africa due to the lack of infrastructural as well as human resources. With the widespread unregulated use of antibiotics in some parts of Africa, the figures of antimicrobial resistance are likely to soar. In the face of these significant challenges, this ‘perspectives’ article aims to address the issue of antimicrobial resistance in Africa, by providing achievable and targeted goals to curb the spread of infection and rising antimicrobial resistance. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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14 pages, 1084 KiB

Open AccessSystematic Review

The Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis

by Ligang Liu, Fang Li, Hekai Shi and Milap C. Nahata

Antibiotics 2023, 12(2), 346; https://doi.org/10.3390/antibiotics12020346 - 07 Feb 2023

Cited by 5 | Viewed by 2799

Abstract

The eradication of Helicobacter pylori (H. pylori) infection remains challenging due to increasing bacterial resistance. Resistance rates to clarithromycin, metronidazole, and levofloxacin were higher than 30% in the USA, making current therapies less effective. Vonoprazan triple therapy (VAC) has demonstrated similar efficacy and [...] Read more.

The eradication of Helicobacter pylori (H. pylori) infection remains challenging due to increasing bacterial resistance. Resistance rates to clarithromycin, metronidazole, and levofloxacin were higher than 30% in the USA, making current therapies less effective. Vonoprazan triple therapy (VAC) has demonstrated similar efficacy and safety profiles compared to PPI-based triple therapy (PPI). However, the eradication rate of vonoprazan dual therapy (VA) for H. pylori infection in comparison to VAC, and PPI was poorly established. Electronic databases were searched up to 6 October 2022, to identify studies examining the safety and efficacy of VA compared to VAC and PPI. Six studies were included. For empiric therapies among treatment naïve patients, VA, VAC, and PPI did not achieve high cure rates (>90%). The comparative efficacy ranking showed VAC was the most effective therapy, followed by VA, and PPI. The results were similar for clarithromycin-resistant infections. The comparative safety ranking showed VA ranked first, whereas PPI triple therapy was the least safe regimen. These findings should guide the selection of the most effective and safe treatment and conduct additional studies to determine the place of vonoprazan dual versus triple therapies in patients with H. pylori from various countries across the world. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)

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