Combating Antimicrobial Resistance and Protecting the Miracle of Modern Medicine (2022) / Chapter Skim
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2 The Scope of the Problem
2 The Scope of the Problem
Pages 29-72
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From page 29... ...
Mobile genetic elements, a plasmid, for example, may carry multiple different resistance genes. The selection of one resistance trait can therefore lead to the co-selection of other traits conveying resistance to other medicines (Lowy, 2009)
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HUMAN ACTION EXACERBATES RESISTANCE Antimicrobials are used frequently in human medicine, the field for which they were developed and the one with the highest, most direct stake in their preservation. Antimicrobials are also widely used in veterinary medicine.
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Associated relative contribution, supporting evidence, and potential population affected (diameter of bubble) was created from a two-round Delphi method of Holmes and colleagues, who identified factors from review of the national and international antimicrobial resistance literature.
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A healthy and diverse microbiome can help control the spread of resistant pathogens by increasing the competition for nutrients and other resources. Be cause antimicrobial treatment alters microbial ecology, there is growing interest in therapeutic steps to restore the microbiome after an infectious disease, as well as therapies that work to combat resistance by moderating host immunity through the microbiome.
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From page 33... ...
the WHO aimed to preserve the effectiveness of powerful, new medicines. Access Group: The first-choice treatments for the 25 most common infections; these 29 medicines are described as "the core set of antibiotics that should be available everywhere." Watch Group: Antibiotics with greater potential for resistance or toxicity; medi cines on this list are highly valuable in human medicine and should not be used in agriculture; their use is routinely monitored to ensure consistency with WHO guidelines.
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. The risk of secondary bacterial infections may drive clinicians to prescribe prophylactic antimicrobials in some patients (Manohar et al., 2020)
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. The Misuse and Overuse of Antimicrobials in Veterinary Medicine Many of the same psychological factors and adherence to outdated treatment guidelines that influence doctors, dentists, and nurses to overuse antimicrobial medicines apply to veterinarians as well.
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The mechanisms through which these medicines promote growth is unclear, but the use of subtherapeutic doses of antibiotics in feed and water was common practice by the 1950s, and highly favorable to selecting for and retaining resistant bacteria (Kirchhelle, 2018; Van et al., 2020; Wall et al., 2016; Woolhouse et al., 2015)
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From page 37... ...
The World Organisation for Animal Health, known by the historical acronym OIE, monitors antimicrobial use in animals; its most recent survey found that only 26 percent of 160 countries still allow the use of antimicrobial growth promoters in livestock -- the lowest proportion since the organization began monitoring (OIE, 2021)
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. By some projections, antimicrobial use in livestock may double total antimicrobial consumption in Brazil, China, India, Rus sia, and South Africa by 2030 (Manyi-Loh et al., 2018; Van Boeckel et al., 2015)
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. Resistant Pathogens Overlap Human and Animal Hosts The extent to which antimicrobial use in farm animals threatens human health is not clear, nor is the direction of this relationship oneway (Muloi et al., 2018)
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. In short, the complexity of potential transmission routes through which resistant bacteria may pass among and between species and the lack of detailed environmental monitoring make it difficult to establish the source of resistant bacteria or resistance genes in a population (Argudin et al., 2017)
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. The potential emergence of resistant pathogens in companion animals and the transmission of these pathogens to humans is not an area that is well studied, however (Joosten et al., 2020)
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Antimicrobial Resistance in the Environment All antimicrobial use, be it in human or veterinary medicine, in terrestrial animals, aquaculture, or crop agriculture, selects for resistance genes. Human and animal waste both contain antimicrobial residues and resistance genes, as does the runoff from pharmaceutical factories.
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. Other research in the United States has found a correlation between human activity, especially animal agriculture, and the concentration of resistance genes in rivers (Pruden et al., 2012)
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. Resistance genes can remain in wastewater after treatment, raising concerns about its use in irrigation and the potential to introduce resistance traits into the environment (Fahrenfeld et al., 2013)
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Concentrations of antibiotic resistance genes in manures are considerably higher than in sewage biosolids (Munir and Xagoraraki, 2011)
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As the previous chapter discussed, the parts of the world that have the highest burden of drug-resistant infections have, not coincidentally, the most serious problems with crowding and infection control that allow infectious diseases to spread quickly among humans and livestock. In 2018, a modest majority (55 percent)
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From page 47... ...
The irony of the problem is that the same factors that drive the high burden of infectious disease, including poor sanitation, lack of primary care, and limited access to medicines, in turn encourage the emergence of resistant pathogens. The prevalence of multidrug resistant organisms, especially E
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. The medicines that treat these pathogens are expensive and often unavailable in low- and middle-income countries, while treating the resistant infection with an ineffective antimicrobial provides selective pressure that encourages the spread of resistant pathogens (Alvarez-Uria et al., 2016)
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. Less can be said about the roughly 122 million surgeries that happen annually in low- and middle-income countries, though evidence indicates rates of surgical site infections to be much higher, affecting roughly 17 percent of surgical patients (Bhangu et al., 2018; Rickard et al., 2020; Stanley, 2020)
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. Despite marked declines over the past 30 years, infectious diseases are still among the leading causes of death for children under 5 worldwide, including over 800,000 deaths from pneumonia and over 500,000 from diarrhea (Dadonaite, 2019; WHO, 2020b)
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. More recent research in seven low- and middle-income countries indicates ampicillin gentamicin is no longer an effective treatment for neonatal sepsis because of high rates of resistance (Thomson et al., 2021)
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Four of the six most problematic, multidrug-resistant pathogens found in hospitals (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are gram-negative bacteria.
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. A global health response will be central to any mitigation strategy, but it is difficult to find transferable strategies from other global health problems, as antimicrobial resistance is not the result of any one pathogen or casual process, but a complex web of related problems, sometimes related only loosely (Hoffman et al., 2020)
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With the exception of their harvest for food, most of the services oysters provide do not have an obvious dollar value. Attempts to quantify the value of the ecosystem services oysters provide have to consider a range of factors, including their filtering sediment and plankton, allowing light to penetrate further into the water, aiding the growth of aquatic plants, and the influence of oysters and their reefs in protecting other fish species.
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From page 55... ...
and the G7 and G20 forums resulted in antimicrobial product development partnerships such as the Global Antibiotic Research and Development Partnerships and CARB-X (officially, the Combating Antibiotic Resistance Biopharmaceutical Accelerator) , discussed in Chapter 6, and the UN High-Level Meeting on Antimicrobial Resistance (Evans, 2017; UN, 2016a)
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. The environmental component of antimicrobial resistance includes not only the watershed and soil management of drug residues and resistance genes, but the likelihood that climate change will aggravate the problem.
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https://wellcome. ac.uk/sites/default/files/antimicrobial-resistance-environment-report.pdf (accessed April 28, 2021)
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The Lancet Infectious Diseases 18(5)
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From page 59... ...
Federal Task Force on Combating Antibiotic-Resistant Bacteria. https://www.hhs.gov/sites/default/files/carb-national action-plan-2020-2025.pdf (accessed April 8, 2021)
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https://www.avma.org/javma-news/2017-05-01/herd-sizes-trade-risk pig-health (accessed April 22, 2021)
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2013. Reclaimed water as a reservoir of antibiotic resistance genes: Distribution system and irrigation implications.
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Lancet Infectious Diseases 19(9)
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2015. Disruption of the gut microbiome: Clostridium difficile infection and the threat of antibiotic resistance.
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Lancet Infectious Diseases 13(12)
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. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC6630404 (accessed April 28, 2021)
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2011. Levels of antibiotic resistance genes in manure, biosolids, and fertilized soil.
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2012. Correlation between upstream human activities and riverine antibiotic resistance genes.
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2020. The norwegian national strategy against antibiotic resistance.
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https://www.birminghamhealthpartners.co.uk/reducing-surgical-site-infection and-antimicrobial-resistance-new-guidelines-issued (accessed April 8, 2021)
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Rome, Italy: Food and Agriculture Organization of the United Nations. https://research online.rvc.ac.uk/id/eprint/10602/1/10602.pdf (accessed April 22, 2021)
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Lancet Infectious Diseases 11(5)
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2017. Continental-scale pollution of estuaries with antibiotic resistance genes.
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