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      Whole Genome Sequencing for Studying Helicobacter pylori Antimicrobial Resistance

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      Antibiotics
      MDPI AG

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          Abstract

          Antibiotic resistance (AMR) is an alarming concern worldwide and Helicobacter pylori, one of the most prevalent bacteria, is not an exception. With antibiotics being its primary therapy, increasing resistance leads to a higher rate of treatment failure. Understanding the genomic mechanisms of resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifampicin through next-generation sequencing-based molecular tools, such as whole genome sequencing (WGS), can be of great value, not only to direct a patient’s treatment, but also to establish and optimize treatment guidelines according to the local epidemiology and to avoid the use of inappropriate antibiotics. WGS approaches allow us to gain insight into the genomic determinants involved in AMR. To this end, different pipelines and platforms are continuously being developed. In this study, we take a more detailed view of the use and progression of WGS for in-depth study of H. pylori’s AMR.

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          Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

          The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.
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            Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions

            BACKGROUND & AIMS: In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. METHODS: We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. RESULTS: We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%–16%) and South-East Asia region (10%; 95% CI, 5%–16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%–13%). There was considerable heterogeneity ( I 2 > 75%) among all analyses—this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23–9.28; P < .001). CONCLUSIONS: Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
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              ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads

              Antimicrobial resistance (AMR) is one of the major threats to human and animal health worldwide, yet few high-throughput tools exist to analyse and predict the resistance of a bacterial isolate from sequencing data. Here we present a new tool, ARIBA, that identifies AMR-associated genes and single nucleotide polymorphisms directly from short reads, and generates detailed and customizable output. The accuracy and advantages of ARIBA over other tools are demonstrated on three datasets from Gram-positive and Gram-negative bacteria, with ARIBA outperforming existing methods.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                ABSNC4
                Antibiotics
                Antibiotics
                MDPI AG
                2079-6382
                July 2023
                June 30 2023
                : 12
                : 7
                : 1135
                Article
                10.3390/antibiotics12071135
                10376898
                37508231
                3c8a417b-803e-4ed5-b6b5-20c59f8f2964
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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