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Analysis of the potential for point-of-care test to enable individualised treatment of infections caused by antimicrobial-resistant and susceptible strains of Neisseria gonorrhoeae: a modelling study

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      Abstract

      Objective

      To create a mathematical model to investigate the treatment impact and economic implications of introducing an antimicrobial resistance point-of-care test (AMR POCT) for gonorrhoea as a way of extending the life of current last-line treatments.

      Design

      Modelling study.

      Setting

      England.

      Population

      Patients accessing sexual health services.

      Interventions

      Incremental impact of introducing a hypothetical AMR POCT that could detect susceptibility to previous first-line antibiotics, for example, ciprofloxacin or penicillin, so that patients are given more tailored treatment, compared with the current situation where all patients are given therapy with ceftriaxone and azithromycin. The hypothetical intervention was assessed using a mathematical model developed in Excel. The model included initial and follow-up attendances, loss to follow-up, use of standard or tailored treatment, time taken to treatment and the costs of testing and treatment.

      Main outcome measures

      Number of doses of ceftriaxone saved, mean time to most appropriate treatment, mean number of visits per (infected) patient, number of patients lost to follow-up and total cost of testing.

      Results

      In the current situation, an estimated 33 431 ceftriaxone treatments are administered annually and 792 gonococcal infections remain untreated due to loss to follow-up. The use of an AMR POCT for ciprofloxacin could reduce these ceftriaxone treatments by 66%, and for an AMR POCT for penicillin by 79%. The mean time for patients receiving an antibiotic treatment is reduced by 2 days in scenarios including POCT and no positive patients remain untreated through eliminating loss to follow-up. Such POCTs are estimated to add £34 million to testing costs, but this does not take into account reductions in costs of repeat attendances and the reuse of older, cheaper antimicrobials.

      Conclusions

      The introduction of AMR POCT could allow clinicians to discern between the majority of gonorrhoea-positive patients with strains that could be treated with older, previously abandoned first-line treatments, and those requiring our current last-line dual therapy. Such tests could extend the useful life of dual ceftriaxone and azithromycin therapy, thus pushing back the time when gonorrhoea may become untreatable.

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      Most cited references 23

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      Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003.

      The Centers for Disease Control and Prevention developed screening and diagnostic testing guidelines for chlamydia and gonorrhea at urethral, rectal, and pharyngeal sites for men who have sex with men (MSM). However, in most clinical settings, rectal chlamydial testing is not performed for MSM, and primarily sexually transmitted disease (STD) clinics alone perform routine rectal and pharyngeal gonorrhea screening for asymptomatic men. We evaluated the prevalence of rectal, urethral, and pharyngeal chlamydial and gonococcal infections among MSM seen at the municipal STD clinic and the gay men's community health center. We also determined the proportion of asymptomatic rectal infections, described the patterns of single and multiple anatomic sites of infection, and evaluated the proportion of chlamydial infections that would be missed and not treated if MSM were not routinely tested for chlamydia. We tested specimens using previously validated nucleic acid amplification tests (NAATs). The prevalence of infection varied by anatomic site (chlamydia: rectal, 7.9%; urethral, 5.2%; and pharyngeal, 1.4%; for gonorrhea, rectal, 6.9%; urethral, 6.0%; and pharyngeal, 9.2%). Approximately 85% of rectal infections were asymptomatic supporting the need for routine screening. Because 53% of chlamydial infections and 64% of gonococcal infections were at nonurethral sites, these infections would be missed and not treated if only urethral screening was performed. In addition, >70% of chlamydial infections would be missed and not treated if MSM were tested only for gonorrhea. Because these infections enhance both HIV transmission and susceptibility, clinical settings serving MSM should evaluate the prevalence of chlamydial and gonococcal infections by anatomic site using validated NAATs.
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        UK national guideline for the management of gonorrhoea in adults, 2011.

         ,  Erich Fitzgerald,   (2011)
        The British Association for Sexual Health and HIV (BASHH) UK gonorrhoea guideline has been updated in 2011. It offers advice on diagnosis, treatment and health promotion for anogenital and pharyngeal gonorrhoea. Nucleic acid amplification tests (NAATs) are now being used more for diagnosis and are increasing detection rates in the pharynx and rectum. First line treatment using ceftriaxone with azithromycin is now advised, along with routine test of cure (TOC). The aim is to slow the spread of resistant gonorrhoea now that fewer antibiotics remain effective. A patient information leaflet has been developed.
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          Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe

          ABSTRACT The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http://www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) community-oriented database infrastructure and analysis tools.
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            Author and article information

            Affiliations
            [1 ] departmentSchool of Veterinary Sciences , University of Bristol, Langford House , Bristol, UK
            [2 ] departmentSchool of Social and Community Medicine , University of Bristol, Oakfield House, Oakfield Grove , Bristol, UK
            [3 ] Aquarius Population Health , London, UK
            [4 ] Duke Fuqua School of Business , Durham, USA
            [5 ] departmentBacteriology Reference Department , National Infection Service, Public Health England , London, UK
            [6 ] departmentThe O’Neill Review on Antimicrobial Resistance , Wellcome Trust , London, UK
            Author notes
            [Correspondence to ] Dr. Katy ME Turner; katy.turner@ 123456bristol.ac.uk
            Journal
            BMJ Open
            BMJ Open
            bmjopen
            bmjopen
            BMJ Open
            BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
            2044-6055
            2017
            14 June 2017
            : 7
            : 6
            28615273
            5734280
            bmjopen-2016-015447
            10.1136/bmjopen-2016-015447
            © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

            This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

            Product
            Funding
            Funded by: FundRef http://dx.doi.org/10.13039/501100000266, Engineering and Physical Sciences Research Council;
            Funded by: NIHR;
            Categories
            Infectious Diseases
            Research
            1506
            1706
            Custom metadata
            unlocked

            Medicine

            point-of-care test, neisseria gonorrhoeae, antimicrobial-resistance

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