Existing evidence on antibiotic resistance exposure and transmission to humans from the environment: a systematic map

Springer Science and Business Media LLC - Tập 11 Số 1
Isobel Catherine Stanton1, Alison Bethel2, Anne Frances Clare Leonard1, William Gaze1, Ruth Garside3
1European Centre for Environment and Human Health, College of Medicine and Health, Penryn Campus, University of Exeter, Penryn, TR10 9FE, UK
2College of Medicine and Health, St Luke’s Campus, University of Exeter, Exeter, EX1 1TX, UK
3European Centre for Environment and Human Health, College of Medicine and Health, Knowledge Spa, University of Exeter, Truro, TR1 3HD, UK

Tóm tắt

Abstract Background Antimicrobial resistance (AMR) is predicted to become the leading cause of death by 2050 with antibiotic resistance being an important component. Anthropogenic pollution introduces antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to the natural environment. Currently, there is limited empirical evidence demonstrating whether humans are exposed to environmental AMR and whether this exposure can result in measurable human health outcomes. In recent years there has been increasing interest in the role of the environment and disparate evidence on transmission of AMR to humans has been generated but there has been no systematic attempt to summarise this. We aim to create two systematic maps that will collate the evidence for (1) the transmission of antibiotic resistance from the natural environment to humans on a global scale and (2) the state of antibiotic resistance in the environment in the United Kingdom. Methods Search strategies were developed for each map. Searches were undertaken in 13 bibliographic databases. Key websites were searched and experts consulted for grey literature. Search results were managed using EndNote X8. Titles and abstracts were screened, followed by the full texts. Articles were double screened at a minimum of 10% at both stages with consistency checking and discussion when disagreements arose. Data extraction occurred in Excel with bespoke forms designed. Data extracted from each selected study included: bibliographic information; study site location; exposure source; exposure route; human health outcome (Map 1); prevalence/percentage/abundance of ARB/antibiotic resistance elements (Map 2) and study design. EviAtlas was used to visualise outputs. Results For Map 1, 40 articles were included, from 11,016 unique articles identified in searches, which investigated transmission of AMR from the environment to humans. Results from Map 1 showed that consumption/ingestion was the most studied transmission route. Exposure (n = 17), infection (n = 16) and colonisation (n = 11) being studied as an outcome a similar number of times, with mortality studied infrequently (n = 2). In addition, E. coli was the most highly studied bacterium (n = 16). For Map 2, we included 62 studies quantifying ARB or resistance elements in the environment in the UK, from 6874 unique articles were identified in the searches. The most highly researched species was mixed communities (n = 32). The most common methodology employed in this research question was phenotypic testing (n = 37). The most commonly reported outcome was the characterisation of ARBs (n = 40), followed by characterisation of ARGs (n = 35). Other genetic elements, such as screening for intI1 (n = 15) (which encodes a Class 1 integron which is used as a proxy for environmental ARGs) and point mutations (n = 1) were less frequently reported. Both maps showed that research was focused towards aquatic environments. Conclusions Both maps can be used by policy makers to show the global (Map 1) and UK (Map 2) research landscapes and provide an overview of the state of AMR in the environment and human health impacts of interacting with the environment. We have also identified (1) clusters of research which may be used to perform meta-analyses and (2) gaps in the evidence base where future primary research should focus.

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Tài liệu tham khảo

Livermore DM. Has the era of untreatable infections arrived? J Antimicrob Chemother. 2009;64:29–36.

O'Neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Review on Antimicrobial resistance. 2014.

Cabinet Office. National Risk Register of Civil Emergencies 2015 edition. 2015.

Cabinet Office. National Risk Register of Civil Emergencies 2017 edition. 2017.

Organisation WH. Antimicrobial resistance. Bull World Health Organ. 2014;61(3):383–94.

Finley RL, et al. The scourge of antibiotic resistance: the important role of the environment. Clin Infect Dis. 2013;57(5):704–10.

Wellington EM, et al. The role of the natural environment in the emergence of antibiotic resistance in gram-negative bacteria. Lancet Infect Dis. 2013;13(2):155–65.

Nhu NTK, et al. The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications. Sci Rep. 2016;6:28291.

O'Neill J. Securing new drugs for future generations: the pipeline of antibiotics. Review on Antimicrobial resistance. 2015.

Gupta SK, Nayak RP. Dry antibiotic pipeline: Regulatory bottlenecks and regulatory reforms. J Pharmacol Pharmacother. 2014;5(1):4–7.

O’Dowd A. Death certificates should record antimicrobial resistance as cause of deaths, says CMO. BMJ. 2018;362:k3832.

Singer AC, et al. Review of Antimicrobial resistance in the environment and its relevance to environmental regulators. Front Microbiol. 2016;7:1728.

De Francesco V, et al. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010;19(4):409–14.

Bell BG, et al. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014;14:13.

Fridkin SK, et al. Surveillance of antimicrobial use and antimicrobial resistance in United States hospitals: project ICARE phase 2. Project Intensive Care Antimicrobial Resistance Epidemiology (ICARE) hospitals. Clin Infect Dis. 1999;29(2):245–52.

Obritsch MD, et al. National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002. Antimicrob Agents Chemother. 2004;48(12):4606–10.

Kumari M, et al. A 5-year surveillance on antimicrobial resistance of Acinetobacter isolates at a level-I trauma centre of India. J Lab Physicians. 2019;11(1):34–8.

Laxminarayan R, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013;13(12):1057–98.

Gaze WH, Depledge M. Antimicrobial resistance: investigating the environmental dimension. Frontiers 2017: Emerging Issues of Environmental Concern. 2017: p. 12–22.

Holmes AH, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 2016;387(10014):176–87.

Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin N Am. 2009;23(4):791–815.

Andersson DI, Hughes D. Evolution of antibiotic resistance at non-lethal drug concentrations. Drug Resist Updates. 2012;15(3):162–72.

Gullberg E, et al. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. MBio. 2014;5(5):e01918.

Gullberg E, et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7(7):e1002158.

Murray AK, et al. Novel insights into selection for antibiotic resistance in complex microbial communities. Bio. 2018;9(4):e00969-18.

Lundstrom SV, et al. Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms. Sci Total Environ. 2016;553:587–95.

Kraupner N, et al. Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial biofilms. Environ Int. 2018;116:255–68.

Murray AK, et al. Dawning of a new ERA: environmental risk assessment of antibiotics and their potential to select for antibiotic resistance. Water Res. 2021;200:117233.

Murray AK, et al. The “SELection End points in Communities of bacTeria” (SELECT) method: a novel experimental assay to facilitate risk assessment of selection for antimicrobial resistance in the environment. Environ Health Perspect. 2020;128(10):107007.

Stanton IC, et al. Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration. Commun Biol. 2020;3(1):467.

Kraupner N, et al. Selective concentrations for trimethoprim resistance in aquatic environments. Environ Int. 2020;144:106083.

Amos GCA, et al. Validated predictive modelling of the environmental resistome. ISME J. 2015;9:1467–76.

Canton R, Jose MGA, Galan JC. CTX-M enzymes: origin and diffusion. Front Microbiol. 2012;3:110.

Ashbolt NJ, et al. Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect. 2013;121(9):993–1001.

Leonard AFC, et al. Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey). Environ Int. 2018;114:326–33.

Mughini-Gras L, et al. Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes: a population-based modelling study. Lancet Planet Health. 2019;3(8):e357–69.

Leonard AFC. Are bacteria in the coastal zone a threat to human health? [Thesis]. University of Exeter. 2016.

Stanton IC, et al. What is the research evidence for antibiotic resistance exposure and transmission to humans from the environment? A systematic map protocol. Environ Evid. 2020;9:12.

Lhermie G, et al. Tradeoffs between resistance to antimicrobials in public health and their use in agriculture: moving towards sustainability assessment. Ecol Econ. 2019;166:106427.

Wernli D, et al. Antimicrobial resistance: the complex challenge of measurement to inform policy and the public. PLoS Med. 2017;14(8):e1002378.

Morris GP, et al. Getting strategic about the environment and health. Public Health. 2006;120(10):889–903.

Hirsch R, et al. Determination of antibiotics in different water compartments via liquid chromatography–electrospray tandem mass spectrometry. J Chromatogr A. 1998;815(2):213–23.

Kostich MS, Batt AL, Lazorchak JM. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation. Environ Pollut. 2014;184:354–9.

Boxall AB, et al. The sorption and transport of a sulphonamide antibiotic in soil systems. Toxicol Lett. 2002;131(1–2):19–28.

Armstrong JL, et al. Antibiotic-resistant bacteria in drinking water. Appl Environ Microbiol. 1981;42(2):277–83.

Schwartz T, et al. Detection of antibiotic-resistant bacteria and their resistance genes in wastewater, surface water, and drinking water biofilms. FEMS Microbiol Ecol. 2003;43(3):325–35.

Boehme S, et al. Occurrence of antibiotic-resistant enterobacteria in agricultural foodstuffs. Mol Nutr Food Res. 2004;48(7):522–31.

Chen Q, et al. Long-term field application of sewage sludge increases the abundance of antibiotic resistance genes in soil. Environ Int. 2016;92–93:1–10.

Marti R, et al. Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest. Appl Environ Microbiol. 2013;79(18):5701–9.

Zhang XX, Zhang T, Fang HH. Antibiotic resistance genes in water environment. Appl Microbiol Biotechnol. 2009;82(3):397–414.

Goulas A, et al. How effective are strategies to control the dissemination of antibiotic resistance in the environment? A systematic review. Environ Evid. 2020;9:4.

Pullin AS, et al. Guidelines and standards for evidence synthesis in environmental management. Version 5. 2018.

Abella J, et al. Integron diversity in bacterial communities of freshwater sediments at different contamination levels. FEMS Microb Ecol. 2015;91(12):fiv140.

Gaze WH, et al. Impacts of anthropogenic activity on the ecology of class 1 integrons and integron-associated genes in the environment. ISME J. 2011;5(8):1253–61.

Gillings MR, et al. Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution. ISME J. 2015;9(6):1269–79.

Jechalke S, et al. Widespread dissemination of class 1 integron components in soils and related ecosystems as revealed by cultivation-independent analysis. Front Microbiol. 2014;4:420.

Kotlarska E, et al. Antibiotic resistance and prevalence of class 1 and 2 integrons in Escherichia coli isolated from two wastewater treatment plants, and their receiving waters (Gulf of Gdansk, Baltic Sea, Poland). Environ Sci Pollut Res Int. 2015;22(3):2018–30.

Fedak KM, et al. Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol. 2015;12:14.

Ayiku L, et al. The medline UK filter: development and validation of a geographic search filter to retrieve research about the UK from OVID medline. Health Info Libr J. 2017;34(3):200–16.

Haddaway NR, et al. EviAtlas: a tool for visualising evidence synthesis databases. Environ Evid. 2019;8(1):22.

Haddaway NR, et al. ROSES flow diagram for systematic maps. Version 1.0. 2017.

Apisarnthanarak A, Khawcharoenporn T, Mundy LM. Patterns of nosocomial infections, multidrug-resistant microorganisms, and mold detection after extensive black-water flooding: a survey from Central Thailand. Infect Control Hosp Epidemiol. 2013;34(8):861–3.

Durojaiye OC, et al. Outbreak of multidrug-resistant Pseudomonas aeruginosa in an intesnive care unit. J Hosp Infect. 2011;78(2):154–5.

Patterson AJ, et al. Distribution of specific tetracycline and erythromycin resistance genes in environmental samples assessed by macroarray detection. Environ Microbiol. 2007;9(3):703–15.

Leonard AFC, et al. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters. Environ Int. 2015;82:92–100.

O’Flaherty E, et al. Human exposure to antibiotic resistant-Escherichia coli through irrigated lettuce. Environ Int. 2019;122:270–80.

Hochedez P, et al. Bacteremia caused by Aeromonas hydrophila complex in the Caribbean Islands of Martinique and Guadeloupe. Am J Trop Med Hyg. 2010;83:1123–7.

Govindaswamy A, et al. Multidrug resistant Elizabethkingia meningoseptica bacteremia—experience from a level 1 trauma centre in India. Intractable Rare Dis Res. 2018;7:172–6.

Edberg SC, et al. Escherichia coli: the best biological drinking water indicator for public health protection. J Appl Microbiol. 2000;88:106S-116S.

Blount ZD. The unexhausted potential of E. coli. Elife. 2015;4:e05826.

von Wintersdorff CJH, et al. Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front Microbiol. 2016;7:173.

De Oliveiera DMP, et al. Antimircrobial resistance in ESKAPE pathogens. Clin Microbiol Rev. 2020;33(3):e00181-19.

Blahna MT, et al. The role of horizontal gene transfer in the spread of trimethoprim–sulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and Canada. J Antimicrob Chemother. 2006;57(4):666–72.

IISD Reporting Services. Summary of the third session of the United Nations Environment Assembly: 4–6 December 2017. Earth Negot Bull. 2017;16:143.

European Commission. Commission Implementing Decision (EU) 2020/1161 of 4 August 2020 establishing a watch list of substances for Union-wide monitoring in the field of water policy pursuant to Directive 2008/105/EC of the European Parliament and of the Council. Official Journal of the European Union. 2020.

European Commission. Development of the first Watch List under the Environmental Quality Standards Directive. 2015.

EFSA BIOHAZ Panel, et al. Scientific opinion on the role played by the environment in the emergence and spread of antimicrobial resistance (AMR) through the food chain. EFSA J. 2021;19(6):e06651.

VMD and PHE. UK One Health Report. Joint report on antibiotic use and antibiotic resistance. 2019.

Scholtus E, Parr E. PATH-SAFE: tracking foodborne pathogens and antimicrobial resistant microbes. Food Standards Agency 2021.

Environment Agency. Chief Scientist’s annual review. 2022.

Madden JR, Hall A, Whiteside MA. Why do many pheasants released in the UK die, and how can we best reduce their natural mortality? Eur J Wildl Res. 2018;64(4):40.

Nuesch-Inderbinen M, et al. Raw meat-based diets for companion animals: a potential source of transmission of pathogenic and antimicrobial-resistant Enterobacteriaceae. R Soc Open Sci. 2019;6(10):191170.

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