Combating Antimicrobial Resistance and Protecting the Miracle of Modern Medicine (2022) / Chapter Skim
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4 Strengthening Surveillance
4 Strengthening Surveillance
Pages 117-164
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From page 117... ...
The targets for monitoring include resistant pathogens or indicator organisms, antimicrobials and their metabolites, resistance genes, and mobile genetic elements. For these reasons the setting feeding into surveillance for antimicrobials includes not just hospitals or clinical microbiology labs, although they are important, but also animal health laboratories, watershed and soil monitoring programs, and routine animal health surveillance.
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From page 118... ...
The last section gives more attention to questions of monitoring resistance in water, sewage, and other environmental reservoirs, with the committee proposing steps to better characterize the relatively neglected environmental dimension of surveillance. SURVEILLANCE SYSTEMS Surveillance systems are critically important for understanding the burden of antimicrobial resistance, detecting the emergence and spread of resistant pathogens, targeting interventions to prevent and control the emergence of resistance, and measuring their effectiveness.
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From page 119... ...
. The CDC's Gonococcal Isolate Surveillance Program, which tracks antimicrobial resistance in gonococcal isolates submitted by 33 health departments across the United States, is an example of sentinel surveillance for resistant pathogens (CDC, 2021a)
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• Record antimicrobial susceptibility test results, ideally making them acces sible to laboratory information management systems at sentinel sites and at human, animal, or environmental reference microbiology laboratories. • Harmonize standards and procedures for collecting and transmitting sus ceptibility and related test results.
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From page 121... ...
. For these countries, a road map to surveillance of resistant pathogens sets out the data governance agreements required, as well as the choice of sentinel sites and coordinating laboratories, even arrangements for storing and transporting isolates and data management (Seale et al., 2017)
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As of April 2021, 109 countries or territories participate in the GLASS antimicrobial resistance surveillance program; 19 of these are also in the program for monitoring antimicrobial consumption, and an additional 2 countries participate in the antimicrobial consumption monitoring only. GLASS represents a relatively low bar for national surveillance and reporting but one that makes surveillance of antimicrobial resistance and use possible in countries where it would not otherwise have been an option.
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. A more recent review identified 71 surveillance networks, mostly in Europe and the Americas, that monitored at least one species of resistant bacteria, though only 26 of these networks appear to be active (Diallo et al., 2020)
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. In an effort to better understand private surveillance networks for antimicrobial resistance, the Wellcome Trust and the Open Data Institute established AMR Register, a clearinghouse for pharmaceutical companies' human surveillance data (AMR Research Initiative, 2021a)
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. Limited internet connectivity is a related challenge, as are the cost of the hardware, software, and staff to support automated surveillance networks (Vong et al., 2017)
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From page 126... ...
SOURCE: Reproduced from Using information technology to improve surveillance of Figure 4-2 antimicrobial resistance in South East Asia, Sirenda Vong, Amaury Anciaux, Anette Hulth, John Stelling, Visanu Thamlikitkul, Sunil Gupta, Jonas M Fuks, K a¯ mini Walia, Pinyo Rattanumpawan, Sergey Eremin, Klara Tisocki, Tika R
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From page 127... ...
Phenotypic antimicrobial susceptibility tests determine the effectiveness of an antimicrobial compound in killing or inhibiting the growth of specific bacterial types. Such test results are vital for clinical decision making, including the drug and regimen for antimicrobial therapy.
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FIGURE 4-3 Steps in disk diffusion. NOTES: In disk diffusion, different antimicrobials or different concentrations of the same antimicrobial are spaced on a culture plate inoculated with the pathogen of interest.
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From page 129... ...
Its usefulness has increased with the introduction of high-throughput, real-time quantitative PCR, a technique that can analyze the presence and quantity of many resistance genes or mobile genetic elements at the same time, performing multiple assays using samples of only nanoliters (Franklin et al., 2021; Luby et al., 2016)
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From page 130... ...
Figure 4-5 nome -- is then compared to a reference database of resistance genes and other determinants of resistance. (Examples of such reference databases include the Comprehensive Antibiotic Resistance Database, ResFiner, and the Reference Gene Catalog [Alcock et al., 2020; Bortolaia et al., 2020; Feldgarden et al., 2021a]
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From page 131... ...
resistance genes Sequence-based metagenomics Functional metagenomics FIGURE 4-6 Examples of metagenomic analysis of antimicrobial resistance in microbial communities. NOTES: Cloning fragments into an expression vector to create a metagenomic Figure expression 4-6is a new approach especially valuable in identifying genes in library volved in resistance to target antimicrobials.
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. While the new highthroughput, real-time PCR techniques can test for multiple resistance genes at the same time, they are incapable of identifying novel resistance genes or emerging genetic elements (Franklin et al., 2021)
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Whole genome Antimicrobial-resistant bacteria Generally, cost prohibitive for sequencing can be typed and tracked by large studies individual allele profile Limited to the individual Achieves much higher resolution bacterial cells that can be than traditional typing methods cultured and sequenced; Determines co-carriage of newer technologies like single specific genes causing different cell genomics can capture multidrug-resistance patterns unculturable microbes Requires accurate and up-to date reference databases Very high technical requirements continued
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From page 134... ...
Does not provide enough sequencing depth to enrich and assemble genomes of a single strain (especially in complex matrices) ; however, this limitation depends on the platform Results dependent on library preparation and bioinformatics workflows Metatranscript- Allows the characterization and Only characterizes resistance omics quantification of antimicrobial genes that are actively resistance genes that are expressed at the particular metabolically active (being time of sample collection and expressed)
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Pathogen identification and susceptibility are confirmed within 48 hours, along with PCR results screening for resistance genes (Chandrasekera et al., 2015)
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at the National Institutes of Health (NIH) , has collected and made publicly available considerable information about resistance genes, genome sequences, antimicrobial susceptibility data, and bacterial genomes (NLM, 2019a)
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The phenotypic information is included as a column in the Isolate Browser next to the column of Figureidentified 4-7 resistance genes, as well as details of the antibiogram, includ ing minimum inhibitory concentrations and the testing standard used. Additional information about the isolates (e.g., clinical or environmental
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. The sequencing of resistance genes and associated mechanisms of resistance can increasingly predict pathogens' susceptibility to different antimicrobials (Hendriksen et al., 2019a; Schurch and van Schaik, 2017)
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hospitals, nursing homes, diagnostic laboratories, and environmental monitoring sites on phenotypic resistance that is not captured by the Pathogen Detection Project because no genomic data are collected to which the phenotypic results can be attached. Even if there are genomic data to which susceptibility results can be linked, adding this information creates an extra manual step on the part of the submitter.
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faecium 100 100 NCBINCBI Pathogen CLC-bio Pathogen CLC-bio DB/BLAST DB/BLAST 20182018 S aureus S
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ESBL: Extended Spectrum Beta-Lactamase, (2) MIC: Minimum Inhibitory Concentration, (3)
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should establish an open-source, unified antimicrobial resistance database that integrates raw phenotypic data from national and international efforts. This database should sup port automatic importation from hospitals, laboratories, and surveillance networks and linking to genotypic data when available.
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The Pathogen Detection Isolate Browser also has a field for susceptibility test phenotypes, listing all the medicines tested against the isolate (NCBI, 2019)
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In a unified antimicrobial resistance database, numerical measurements or ranges of minimum inhibitory concentrations would be a crucial data field. Simply knowing that a pathogen is sensitive to a treatment is sufficient to guide therapy, but some susceptible pathogens are much closer to developing resistance than others.
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MONITORING ANTIMICROBIAL RESISTANCE IN WATER Increasing the availability of information about environmental isolates collected by surveillance networks and stored in the proposed NLM database would contribute to a more holistic understanding of antimicro
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From page 146... ...
. The geographic scale of the area to be monitored adds to the challenge, as do the numerous targets for surveillance of antimicrobial resistance (e.g., pathogens, resistance genes, antimicrobials and residues, mobile genetic elements)
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. In low- and middle-income countries metagenomic analysis of sewage samples has shown the relative abundance of resistance genes expressed are broadly consistent with patterns of antimicrobial use (i.e., genes that convey resistance to macrolide antibacterials are more abundant in places where macrolides are more commonly used)
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From page 148... ...
The program has already made considerable progress in setting out standard meth ods to prepare, store, and transport sewage samples, standardized procedures for extracting and measuring RNA, as well as laboratory controls on the process. The system for wastewater monitoring could be adapted to monitor resistant pathogens and resistance genes.
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2017. Toward a comprehensive strategy to mitigate dissemination of environmental sources of antibiotic resistance.
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The authors also suggested six bacterial groups as priorities for water monitoring efforts because of their likelihood to carry resistance genes or acquire them from environmental sources,4 their usefulness as indicators of water quality, and their frequency in both animal gut and environmental samples (Berendonk et al., 2015)
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. Monitoring Point Source Discharge While useful, surface water monitoring does not give insight into the source of the resistance genes, resistant pathogens, or medicine residues in the environment.
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. Whether hospital effluent contributes disproportionately to the presence of antimicrobial resistance genes in wastewater treatment plants is as yet an unresolved scientific question, however (Buelow et al., 2018; Kraupner et al., 2021; Muller et al., 2018)
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This monitoring will contribute to better linking of resistance indicators in waste to those found downstream in surface waters. Information from the proposed surveillance would, if included in the NCBI Pathogen Detection Database and the proposed NLM database described in Recommendation 4-1, contribute to a more complete mapping of the geographic distribution of resistance genes.
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. There is evidence that current action at these plants can reduce the abundance of some resistance genes, though genes associated with resistance to vancomycin are notably unaffected (Parnanen et al., 2019)
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2010. Call of the wild: Antibiotic resistance genes in natural environments.
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2021. Comparison of antibiotic resistance in the influent and effluent of two wastewater treatment plants.
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2019. Antibiotic resistance genes in treated wastewater and in the receiving water bodies: A pan-European survey of urban settings.
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Food and Agriculture Organization of the United Nations. https://www.fao.org/3/ne859en/ne859en.pdf (accessed July 30, 2021)
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2018. Geospatial distribution of antimicro bial resistance genes in us rivers and streams.
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2019. A conceptual framework for the environmental surveillance of antibiotics and antibiotic resistance.
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2011. Ter tiary-treated municipal wastewater is a significant point source of antibiotic resistance genes into Duluth-Superior harbor.
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2019. Antibiotic resistance in European wastewater treatment plants mirrors the pattern of clinical antibiotic resistance prevalence.
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2017. Challenges and opportunities for whole-genome sequencing-based surveillance of antibiotic resistance.
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2009. Antibiotic resistance genes in water environ ment.
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