Dataset Information

Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study.

ABSTRACT: Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due to widespread over- and misuse of antimicrobials, there has been an alarming increase in global resistance, for which a standardized methodology for geographic surveillance would be highly beneficial. To demonstrate that a standardized methodology could be used to provide molecular surveillance of antimicrobial resistance (AMR) genes, we initiated a pilot study to test 130 diarrheal pathogens (Campylobacter spp., Escherichia coli, Salmonella, and Shigella spp.) from the USA, Peru, Egypt, Cambodia, and Kenya for the presence/absence of over 200 AMR determinants. We detected a total of 55 different determinants conferring resistance to ten different categories of antimicrobials: genes detected in ? 25 samples included blaTEM, tet(A), tet(B), mac(A), mac(B), aadA1/A2, strA, strB, sul1, sul2, qacE?1, cmr, and dfrA1. The number of determinants per strain ranged from none (several Campylobacter spp. strains) to sixteen, with isolates from Egypt harboring a wider variety and greater number of genes per isolate than other sites. Two samples harbored carbapenemase genes, blaOXA-48 or blaNDM. Genes conferring resistance to azithromycin (ere(A), mph(A)/mph(K), erm(B)), a first-line therapeutic for severe diarrhea, were detected in over 10% of all Enterobacteriaceae tested: these included >25% of the Enterobacteriaceae from Egypt and Kenya. Forty-six percent of the Egyptian Enterobacteriaceae harbored genes encoding CTX-M-1 or CTX-M-9 families of extended-spectrum ?-lactamases. Overall, the data provide cross-comparable resistome information to establish regional trends in support of international surveillance activities and potentially guide geospatially informed medical care.

SUBMITTER: Taitt CR

PROVIDER: S-EPMC7460656 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study.

Taitt Chris R CR Leski Tomasz A TA Prouty Michael G MG Ford Gavin W GW Heang Vireak V House Brent L BL Levin Samuel Y SY Curry Jennifer A JA Mansour Adel A Mohammady Hanan El HE Wasfy Momtaz M Tilley Drake Hamilton DH Gregory Michael J MJ Kasper Matthew R MR Regeimbal James J Rios Paul P Pimentel Guillermo G Danboise Brook A BA Hulseberg Christine E CE Odundo Elizabeth A EA Ombogo Abigael N AN Cheruiyot Erick K EK Philip Cliff O CO Vora Gary J GJ

International journal of molecular sciences 20200818 16

Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due to widespread over- and misuse of antimicrobials, there has been an alarming increase in global resistance, for which a standardized methodology for geographic surveillance would be highly beneficial. ...[more]

PMID: 32824772

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Project description:The aim of this study is to characterize the antimicrobial resistance of Campylobacter jejuni recovered from diarrheal patients in Belgium, focusing on the genetic diversity of resistant strains and underlying molecular mechanisms of resistance among Campylobacter jejuni resistant strains isolated from diarrheal patients in Belgium. Susceptibility profile of 199 clinical C. jejuni isolates was determined by minimum inhibitory concentrations against six commonly-used antibiotics (ciprofloxacin, nalidixic acid, tetracycline, streptomycin, gentamicin, and erythromycin). High rates of resistance were observed against nalidixic acid (56.3%), ciprofloxacin (55.8%) and tetracycline (49.7%); these rates were similar to those obtained from different national reports in broilers intended for human consumption. Alternatively, lower resistance rates to streptomycin (4.5%) and erythromycin (2%), and absolute sensitivity to gentamicin were observed. C. jejuni isolates resistant to tetracycline or quinolones (ciprofloxacin and/or nalidixic acid) were screened for the presence of the tetO gene and the C257T mutation in the quinolone resistance determining region (QRDR) of the gyrase gene gyrA, respectively. Interestingly, some of the isolates that displayed phenotypic resistance to these antimicrobials lacked the corresponding genetic determinants. Among erythromycin-resistant isolates, a diverse array of potential molecular resistance mechanisms was investigated, including the presence of ermB and mutations in the 23S rRNA gene, the rplD and rplV ribosomal genes, and the regulatory region of the cmeABC operon. Two of the four erythromycin-resistant isolates harboured the A2075G transition mutation in the 23S rRNA gene; one of these isolates exhibited further mutations in rplD, rplV and in the cmeABC regulatory region. This study expands the current understanding of how different genetic determinants and particular clones shape the epidemiology of antimicrobial resistance in C. jejuni in Belgium. It also reveals many questions in need of further investigation, such as the role of other undetermined molecular mechanisms that may potentially contribute to the antimicrobial resistance of Campylobacter.

Project description:ObjectivesDespite escalating antimicrobial resistance (AMR), implementing effective antimicrobial optimisation within healthcare settings has been hampered by institutional impediments. This study sought to examine, from a hospital management and governance perspective, why healthcare providers may find it challenging to enact changes needed to address rising AMR.DesignSemistructured qualitative interviews around their experiences of antimicrobial stewardship (AMS) and responsiveness to the requirement for optimisation. Data were analysed using the framework approach.SettingTwo metropolitan tertiary-referral hospitals in Australia.ParticipantsTwenty hospital managers and executives from the organisational level of department head and above, spanning a range of professional backgrounds and in both clinical and non-clinical roles, and different professional streams were represented.ResultsThematic analysis demonstrated three key domains which managers and executives describe, and which might function to delimit institutional responsiveness to present and future AMR solutions. First, the primacy of 'political' priorities. AMR was perceived as a secondary priority, overshadowed by political priorities determined beyond the hospital by state health departments/ministries and election cycles. Second, the limits of accreditation as a mechanism for change. Hospital accreditation processes and regulatory structures were not sufficient to induce efficacious AMS. Third, a culture of acute problem 'solving' rather than future proofing. A culture of reactivity was described across government and healthcare institutions, precluding longer term objectives, like addressing the AMR crisis.ConclusionThere are dynamics between political and health service institutions, as well as enduring governance norms, that may significantly shape capacity to enact AMS and respond to AMR. Until these issues are addressed, and the field moves beyond individual behaviour modification models, antimicrobial misuse will likely continue, and stewardship is likely to have a limited impact.

Project description:Antimicrobial resistance (AMR) is a global health threat, and antimicrobial usage and AMR in animal production is one of its contributing sources. Poultry is one of the most widespread types of meat consumed worldwide. Poultry flocks are often raised under intensive conditions using large amounts of antimicrobials to prevent and to treat disease, as well as for growth promotion. Antimicrobial resistant poultry pathogens may result in treatment failure, leading to economic losses, but also be a source of resistant bacteria/genes (including zoonotic bacteria) that may represent a risk to human health. Here we reviewed data on AMR in 12 poultry pathogens, including avian pathogenic Escherichia coli (APEC), Salmonella Pullorum/Gallinarum, Pasteurella multocida, Avibacterium paragallinarum, Gallibacterium anatis, Ornitobacterium rhinotracheale (ORT), Bordetella avium, Clostridium perfringens, Mycoplasma spp., Erysipelothrix rhusiopathiae, and Riemerella anatipestifer. A number of studies have demonstrated increases in resistance over time for S. Pullorum/Gallinarum, M. gallisepticum, and G. anatis. Among Enterobacteriaceae, APEC isolates displayed considerably higher levels of AMR compared with S. Pullorum/Gallinarum, with prevalence of resistance over >80% for ampicillin, amoxicillin, tetracycline across studies. Among the Gram-negative, non-Enterobacteriaceae pathogens, ORT had the highest levels of phenotypic resistance with median levels of AMR against co-trimoxazole, enrofloxacin, gentamicin, amoxicillin, and ceftiofur all exceeding 50%. In contrast, levels of resistance among P. multocida isolates were less than 20% for all antimicrobials. The study highlights considerable disparities in methodologies, as well as in criteria for phenotypic antimicrobial susceptibility testing and result interpretation. It is necessary to increase efforts to harmonize testing practices, and to promote free access to data on AMR in order to improve treatment guidelines as well as to monitor the evolution of AMR in poultry bacterial pathogens.

Dataset Information

Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study.

Publications

Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study.

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