7

The National Action Plan for Combating Antibiotic-Resistant Bacteria

The need for a coordinated and cohesive approach to preventing, detecting, and controlling infections related to antimicrobial-resistant pathogens is a national and international concern. The need was the basis of the 2015 World Health Assembly resolution on antimicrobial resistance, which encouraged countries to develop national action plans and to collaborate with other countries in their implementation (Shallcross and Davies, 2014). This chapter describes the U.S. government’s work since 2015 to combat antimicrobial resistance in the United States and internationally. To advance this analysis, the committee commissioned the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota to review agencies’ progress against the National Action Plan for Combating Antibiotic-Resistant Bacteria 2015–2020. This chapter will first review this action plan, its goals, and its implementation. Next, it will review the Government Accountability Office (GAO) report on progress made with regard to antibiotic resistance and human health. The following section reviews the CIDRAP commissioned analysis. The last section of the chapter discusses the recently released National Action Plan for Combating Antibiotic-Resistant Bacteria 2020–2025, including the new objectives and milestones set for the federal government over the next 5 years. The chapter concludes with a brief assessment of progress made by the federal government in preventing, controlling, and treating antimicrobial resistance in the United States and around the world and identifies the major challenges the agencies have encountered in this work.

THE 2015 NATIONAL ACTION PLAN

In September 2014, the White House released a National Strategy for Combating Antibiotic-Resistant Bacteria (The White House, 2014). This document identified the federal government’s priorities to prevent, detect, and control outbreaks of resistant pathogens recognized by the Centers for Disease Control and Prevention (CDC) as urgent or serious threats (The White House, 2014). The strategy also put considerable emphasis on the continued availability of effective therapies for the treatment of bacterial infections and the ability to detect and control emerging resistant pathogens in humans and animals (The White House, 2014). Box 7-1 lists the goals and objectives set out in the first national strategy document, goals that were further divided into subobjectives and milestones for the first, third, and fifth years of the plan.

The National Action Plan for Combating Antibiotic-Resistant Bacteria 2015–2020 (hereafter, the 2015 action plan), provided agencies with a road map to achieve the goals shown in Box 7-1 (The White House, 2015). The 2015 action plan also included national targets, as determined by the CDC, that the plan aimed to achieve by 2020. These targets were categorized as responding to CDC-recognized urgent threats and CDC-recognized serious threats (see Box 7-2). These quantitative targets were intended to reduce the incidence of threats to both human and animal health, particularly for carbapenem-resistant Enterobacterales, methicillin-resistant Staphylococcus aureus, and Clostridioides difficile. For each goal in the action plan, there are several (two to six) expected outcomes that might reasonably follow the achievement of the cited milestones. Several of these outcomes are quantitative, such as a percentage reduction in inappropriate antibacterial prescriptions (The White House, 2015). But most of the expected outcomes listed are process outcomes, such as developing a global database to collect information on antimicrobial use in animals (The White House, 2015).

The 2015 action plan also created a federal government task force, co-chaired by the secretaries of defense, agriculture, and health and human services, charged with monitoring progress against cited goals and objectives and updating the president on their progress every year (The White House, 2015). The action plan also set out 230 milestones, spread among each of the five goals to be achieved in the first, third, or last year of the plan (Moore, 2021).

Federal agencies identified in the action plan include the Department of Health and Human Services (HHS) and its agencies,¹ the Department of Defense (DOD), the Department of Veterans Affairs (VA), the U.S. Department of Agriculture (USDA),² the Environmental Protection Agency (EPA), the U.S. Agency for International Development (USAID), and the Department of State (The White House, 2015). Many of the milestones in the 2015 action plan require collaboration among agencies or departments. For example, subobjective 4.1.2 states that within 1 year “FDA, USDA, CDC, and NIH will bring together experts in food production, agriculture, and public health to encourage collaborative research—from basic research to clinical testing—on antibiotic resistance” (The White House, 2015, p. 42). However, such milestones are vague, subject to interpretation, and lack a defined or measurable outcome against which to determine success. Furthermore, for many of the targets outlined in Box 7-2, it is not evident that there are baseline measures against which the targets could be measured.

Some of the cited goals and milestones require input and dissemination from professional associations such as the American Veterinary Medical Association and various state and regional organizations. The 2015 action plan also sets specific milestones for some states, as well as Puerto Rico and the District of Columbia (The White House, 2015). Finally, many of the federal agencies are called on to work with multilaterals such as the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations, and the World Organisation for Animal Health to develop a variety of databases, systems, and capacities to meet the action plan goals (The White House, 2015).

Many of the milestones in the 2015 action plan involve data tracking and sharing and laboratory surveillance or goals that depend on coordinated effort across government agencies and at various levels (i.e., federal, state, county) (The White House, 2015). This need for coordina-

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¹ Including the Centers for Medicare & Medicaid Services (CMS), the Centers for Disease Prevention and Control (CDC), the Agency for Healthcare Research and Quality (AHRQ), the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and the Biomedical Advanced Research and Development Authority (BARDA).

² Including the Animal and Plant Health Inspection Service, the Agricultural Research Service, and the Food Safety Inspection Service.

tion is reflected across the 2015 action plan. For example, under the goal of strengthening One Health surveillance, there were milestones on integrating data from the National Healthcare Safety Network, the Emerging Infections Program, the National Antimicrobial Resistance Monitoring System, the National Animal Health Monitoring System, the National Animal Health Laboratory Network, and the Veterinary Laboratory Investigation and Response Network. The advancing of One Health surveillance was also tied to the creation of a regional network of public health laboratories with standardized methods for testing, and monitoring antimicrobial sales, use, and emerging resistance across the food production system (The White House, 2015).

The agencies implementing the 2015 action plan published regular progress reports (USTFCARB, 2017, 2018, 2019). These progress reports summarize the major activities advancing the 2015 action plan, but not information on specific milestones.

GOVERNMENT ACCOUNTABILITY OFFICE REPORTS

Between 2017 and 2020, GAO reviewed the progress of federal agencies against the 2015 action plan. The 2020 report looked closely at CDC’s surveillance work, as well as federal efforts to encourage diagnostic testing, the development of new treatments for resistant infections, and the promotion of antimicrobial stewardship (GAO, 2020). GAO (2017) reviewed the use of medically important antimicrobials in animal agriculture in a 2017 report.

Key Findings from the Government Accountability Office 2020 Report

After reviewing relevant literature and interviewing involved officials, the GAO report summarized the progress the various agencies had made against their milestones. The report noted four important challenges the agencies faced in implementing the action plan. First, despite expanded surveillance, the CDC still faces an uphill battle in measuring the magnitude of the problem (GAO, 2020). Despite expanding surveillance for its priority bacteria via collaborative systems with state and local health partners, the report concluded, “[T]he precise magnitude and trend in antibiotic resistance are unknown” (GAO, 2020). A lack of a central surveillance system is part of the problem, as various divisions at the CDC are responsible for tracking different infections and diseases. In response to the 2015 action plan, the CDC has established several new networks to assess the scope of antimicrobial resistance such as the Antibiotic Resistance Laboratory Network in 2016, the Emerging Infections Program, and the Enhanced Gonococcal Isolate Surveillance Program. Nevertheless, hospital participation in the National Healthcare Safety

Network was found to be low and the resistant gonorrhea surveillance system perhaps not representative of the general population (GAO, 2020). GAO also found that testing for resistance in clinical practice is often not up to date and laboratories may report only the interpretation of a test (e.g., pathogen susceptible or resistant to antimicrobial) rather than the more useful quantitative test results (GAO, 2020). The report also commented on the difficulties the CDC faces in assembling accurate data for prompt inclusion in its Threats Reports (GAO, 2020).

The report also commented on the challenges associated with diagnostic testing, emphasizing the need for rapid, point-of-care tests, especially for resistant gonorrhea and resistant Campylobacter (GAO, 2020). Rapid tests to distinguish viral from bacterial infections are also urgently needed and called for in the 2015 action plan. To this end, both HHS and DOD are investing in diagnostics development (GAO, 2020). Many of HHS’s efforts, via NIH and BARDA, are focused on supporting the federal biopharmaceutical accelerator program, CARB-X (officially, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) (GAO, 2020). GAO found that despite supporting important research and reducing duplicative research funding, HHS had not given sufficient attention to the managing of clinical outcomes research, something “important for encouraging the use of diagnostic tests for antibiotic resistance, among other things, because such studies can demonstrate the benefits of those tests” (GAO, 2020, p. 38). FDA also has a role in advancing diagnostic testing. The report commended FDA on its efforts to recognize the Clinical and Laboratory Standards Institute’s interpretive criteria for antimicrobial susceptibility testing (information that companies rely on to bring new tests to market), a topic discussed further in Chapter 5 (GAO, 2020). FDA has also made some gains in determining whether laboratories are using up-to-date criteria for susceptibility testing (GAO, 2020).

The GAO report commented on the dearth of antibacterial classes available to treat resistant infections, finding the current drug pipeline to be insufficient, possibly because of the cost of antimicrobial development and regulatory barriers (GAO, 2020). The relatively low cost of many antibiotics, their use for short periods of time, and the often small number of patients who require them are all disincentives for companies to invest in the field. FDA commented on the additional challenges of conducting clinical trials, demonstrating clinical value, and gaining approval for multiple indications, all topics discussed in Chapter 6. Overall, GAO found these incentives to be inadequate. HHS did not agree, however, that post-market financial rewards should be paid for the development of new antimicrobials (GAO, 2020).

The GAO report also gave some attention to antimicrobial stewardship programs. It found the Centers for Medicare & Medicaid Services (CMS), DOD, and the VA had strengthened stewardship in hospitals and

nursing homes. CMS incentives for appropriate clinical use of antimicrobials were also well received, as were Agency for Healthcare Research and Quality (AHRQ) and CDC stewardship guidance documents (GAO, 2020). Based on its analysis, GAO made eight recommendations on how to improve progress against the goals and objectives of the 2015 action plan, shown in Box 7-3 (GAO, 2020).

Key Findings from the Government Accountability Office 2017 Report

The 2017 GAO report on the use of pharmaceuticals in animals found that since the agency’s previous report in 2011 FDA had increased veterinary oversight of antimicrobials and was engaged in promising work on label changes for veterinary antimicrobials, though these changes were

not fully implemented in 2017 (GAO, 2017). The report also described joint efforts by FDA and USDA to improve data collection on antimicrobial use and resistant infections in food-producing animals. To a similar end, the report reiterated a 2011 recommendation that HHS and USDA monitor antimicrobial use and resistance on farms, noting that neither FDA nor USDA’s Animal and Plant Health Inspection Service “have metrics to assess the impact of actions they have taken, which is inconsistent with leading practices for performance measurement” (GAO, 2017).

The GAO report commented on a lack of a clear framework to determine when farm-level investigations of foodborne illnesses would be necessary, suggesting that the CDC, USDA, and other stakeholders coordinate to develop such guidance and identify factors that contribute to or cause foodborne illness including illnesses caused by resistant pathogens (GAO, 2017). Box 7-4 shows the recommendations from the 2017 GAO report.

FEDERAL GOVERNMENT IMPLEMENTATION OF THE 2015 NATIONAL ACTION PLAN

To better understand agencies’ successes and failures in implementing the 2015 national action plan, the committee commissioned an independent analysis from CIDRAP. This analysis is available as an online supplement at https://www.nap.edu/resource/26350/Background_Analysis.pdf.

After review of publicly available progress reports and consultation with agency staff, the CIDRAP analysis found that, according to the agencies’ self-assessments, 93 percent of the 230 milestones laid out in 2015 action plan were completed successfully and on time, while 2.5 percent were partially completed, another 2.5 percent still in progress, and only 2 percent not achieved (Moore, 2021) (see Table 7-1). The committee cautions that interpretation of this seemingly exceptional success should be carefully qualified. The number of agencies involved and the number of actions assigned to them made it necessary for CIDRAP investigators to rely heav-

TABLE 7-1
Summary of Federal Agency 2015 Action Plan Milestones and Progress Toward Achieving Them

^a Many of the milestones involved participation by more than one agency, so the total number of milestones presented in this table exceeds the 230 milestones in the 2015 action plan because of the overlap among agencies (Moore, 2021)

^b For milestones that are in progress, USDA and FDA milestones overlap, so there are only three different milestones for these two agencies, giving a total of six milestones that were in progress at the time of this report (Moore, 2021).

^c This applies to the following milestone under Goal 4, Objective 4.1: “On an annual basis: HHS, NIH, FDA, USDA, CDC, DOD, and EPA will conduct a review to ensure that U.S. government research resources are focused on high-priority antibiotic resistance issues (including basic research on the emergence and spread of resistance genes) and facilitate use of advanced technologies in research on antibiotic resistance (e.g., whole genome sequencing, proteomics, metagenomics, structural biology, bioinformatics).” The EPA had a minor role in the 2015–2020 action plan and did not have a research agenda or budget for antimicrobial resistance-related activities; therefore, no annual review was undertaken because no resources were focused on antimicrobial resistance. As result, CIDRAP decided to classify this milestone as “not applicable” for the EPA. This milestone was completed for all of the other federal agencies listed, so this milestone was categorized as completed in the overall table

SOURCE: Moore, 2021.

ily on the agency staffs’ own analysis of their progress. This is not, therefore, an impartial analysis. It is likely that a disinterested observer could reach different conclusions regarding how well agencies had implemented the

TABLE 7-2
Summary of Federal Agencies Progress and Challenges Implementing the National Action Plan for Combating Antimicrobial-Resistant Bacteria 2015–2020

NOTE: AHRQ = Agency for Healthcare Research and Quality; BARDA = Biomedical Advanced Research and Development Authority; CDC = Centers for Disease Control and Prevention; CMS = Centers for Medicare & Medicaid Services; DOD = U.S. Department of Defense; EPA = U.S. Environmental Protection Agency; FDA = U.S. Food and Drug Administration; HHS = U.S. Department of Health and Human Service; NIH = National Institutes of Health; USAID = U.S. Agency for International Development; USDA = U.S. Department of Agriculture; VA = U.S. Department of Veterans Affairs.

2015 action plan and, more importantly, if the work was effective at advancing the plan’s ultimate goals.

Table 7-2 lists selected highlights of each agency’s accomplishments in this time.

Readers seeking more detail should consult the CIDRAP final report in the online supplement available at https://www.nap.edu/resource/26350/Background_Analysis.pdf.

Agencies’ Self-Reported Key Challenges

The CIDRAP analysis, which relied heavily on agencies’ self-reporting, found that few agencies had indicated substantial challenges in achieving the assigned milestones under the 2015 action plan and that the vast majority were accomplished on time (Moore, 2021). This finding was not accompanied by independent confirmation of agencies’ progress, however.

The committee found the CIDRAP analysis to be helpful in summarizing the various agencies’ milestones and their activities in response to the 2015 action plan and appreciates that obtaining data to measure actual progress toward the agencies’ milestones would be difficult and labor intensive. Nevertheless, such data would highlight areas where more work is needed. It would also allow for better clarity as to which milestones are relatively straightforward and which ones are difficult. While the CIDRAP report provides an overview of agencies’ activities in response to the 2015 action plan, its reliance on self-reporting and agency review could have introduced considerable bias into its findings. This analysis gives good insight into the scope of the work agencies took on in response to the 2015 action plan, but it is not an independent assessment of their work or achievements.

The CDC, for example, indicated that it has accomplished 89 of its 92 milestones and reported only 2 milestones as incomplete (conducting two randomized control trials to prevent the spread of multidrug-resistant tuberculosis) (Moore, 2021). The CDC was to establish up to 10 new sites to monitor drug-resistant pathogens as part of its Emerging Infections Program. The agency was not able to expand the program, however, citing limited resources, although it did increase the number of pathogens being reported by existing sites (Moore, 2021). This raises other questions, such as how and when expansion would proceed if funding were to become available, or what steps might be taken to ensure a representative cross-section of sites was chosen.

CMS participants noted that although the agency expanded requirements on antibiotic stewardship to hospitals as of 2019, it had not expanded the conditions of participation for dialysis centers, ambulatory surgery centers, and other sites. No explanation for the lack of expansion was

given (Moore, 2021). Similarly, CMS efforts to monitor antimicrobial use through changes to the Inpatient Quality Reporting rules of the National Healthcare Safety Network were described as incomplete because “other issues [took] priority,” but the respondents indicated that a formal rule may not be necessary if voluntary participation were good (Moore, 2021). It would be helpful to understand how the success of voluntary reporting was evaluated or what criteria might be used to determine if a reporting rule were necessary.

The DOD Chemical Biological Defense Program and the Defense Threat Reduction Agency were meant to fund a new antimicrobial to the investigational new drug stage but did not as its lead candidate failed toxicological studies (Moore, 2021).

USDA indicated that, as of spring 2021, two of its milestones were still in progress and two were partially complete. These involved implementation research on antimicrobial stewardship on farms and how the 2017 Veterinary Feed Directive changed practices. After initial surveys in 2016, a funding lapse prevented further work (Moore, 2021). The COVID-19 pandemic also prevented some monitoring of changes in antimicrobial stewardship in livestock (Moore, 2021).

USDA was also called on to provide veterinary accreditation training modules for use in low- or middle-income countries. This training would increase ability to monitor resistance and report outbreaks to the WHO and other stakeholders. USDA reported this task as partially completed. Despite having translated training materials into Spanish, it has not had funding to translate training materials into other languages (Moore, 2021).

NATIONAL ACTION PLAN FOR COMBATING ANTIBIOTIC-RESISTANT BACTERIA, 2020–2025

The National Action Plan for Combating Antibiotic-Resistant Bacteria, 2020–2025 (hereafter, the 2020 action plan) builds on the 2015–2020 action plan (FTF CARB, 2020). The 2015 action plan required federal and local departments and agencies and their partners to establish processes, especially processes for collaboration among agencies, with the private sector, and internationally, and set baseline measures. The 2020 action plan builds on the successes of the 2015 action plan and lays out a strategy for combating antibiotic resistance over the next 5 years. The goals of the 2020 action plan mirror the five goals of the 2015 action plan, but with updated targets and objectives to reflect the progress and challenges of the prior plan. Box 7-5 summarizes how the 2020 action plan will work.

The 2020 action plan has a greater One Health emphasis, though this does not translate, for example, into a greater role for the EPA (PCAST, 2020). The committee also notes that the relationship between climate

change and antimicrobial resistance is not mentioned in the 2020 action plan, a serious concern given the potential for direct effects on water, soil, agriculture, and livestock. Climate change could also provoke migration of humans, their domestic animals, and wildlife, which will have implications for the spread of microbial pathogens (Podesta, 2019; Rojas-Downing et al., 2017; Seebacher and Post, 2015). A One Health orientation to the problem can be challenging to put into practice, but more explicit attention to the ways in which various agencies’ work may be influenced by climate change could help make this One Health framework more concrete.

Implementing the 2020 Action Plan

The 2020 action plan clearly lays out future challenges inherent to the global problem of antimicrobial resistance. Box 7-6 shows some of the challenges to reaching these goals, many informed by the experience of implementing the 2015 action plan.

Addressing the challenges shown in Box 7-6 requires an understanding of what outcomes will be most useful in determining success and how those outcomes will be measured. Many of the action plan’s targets already have measurable outcomes for federal agencies, and each agency or department is to report progress on meeting its outcomes on an annual

basis. At the same time, some targets are open ended, and the agency that is responsible for meeting the target is not specified.³ In such cases it is difficult to establish accountability for outcomes or to know which agency will and which will not support a given milestone. Other objectives may be difficult to achieve because they are vague or not amenable to evaluation, such as increasing surveillance networks capacity to control outbreaks. It is difficult to know how such progress might be measured and if the measurements would be objective. The committee acknowledges that measurable outcomes are not necessarily useful ones. For example, a target of supporting 1,000 publications on antimicrobial resistance by 2021, though measurable and specific, is of questionable value. It is also arguably unrealistic given that 2020 national strategy was only published in 2021 (FTF CARB, 2020).

This is not to say that meaningful outcomes related to antimicrobial resistance are immeasurable. The CDC (2019) Antibiotic Resistance Threats in the United States, 2019 report documented changes in the burden of resistant infections, including drawing attention to areas where targets had not been met. For example, although the 2015 action plan set a target of reducing methicillin-resistant Staphylococcus aureus 50 percent by 2020 (relative to 2011 levels), the 2019 report cited only a 21 percent reduction (CDC, 2019). The same pattern held for infections from multiresistant Pseudomonas aeruginosa, falling 6 percentage points short of the target (CDC, 2019). The report also indicated that despite progress on some pathogens, there was a 315 percent increase in the number of infections associated with erythromycin-resistant invasive group A Streptococcus and a 124 percent increase in drug-resistant Neisseria gonorrhoeae infections (CDC, 2019).

It would also be helpful to track expenditures in support of the action plan and report these annually. This process would give evidence for continued support for the program at the level of agency leadership and Congress. It could also highlight areas of effective and efficient achievement that might be replicated in other agencies.

The committee supports the systematic quantitative and qualitative tracking of activities and outcomes related to the milestones and goals presented in the 2020 action plan. Independent development and assessment of these goals would not only help the United States but also its international partners to understand the best and most effective strategies to combat antimicrobial resistance.

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³ For example, for goal 3, objective 2.1, to stimulate research on the appropriate use of diagnostics and AHRQ, CDC, NIH, and DOD are to “invite research applications and support research on the appropriate use of CARB-related diagnostics in human clinical and veterinary care” (FTF CARB, 2020).

Recommendation 7-1: Congress should direct the Government Accountability Office (GAO) to conduct biennial evaluations of federal agencies’ progress toward meeting the goals of the 2020–2025 National Action Plan for Combating Antibiotic-Resistant Bacteria to ensure objective assessment of agencies’ activities. Congress and GAO should consider ways to use their evaluations to direct course corrections when necessary.

Both the 2015 and the 2020 action plans call on the U.S. government to report on progress. The federal Task Force for Combating Antibiotic-Resistant Bacteria prepared annual progress reports under the 2015 action plan. These are essentially self-reports, however. While helpful, such reports are not necessarily objective or comprehensive. As the task force explained, they are intended to provide “a narrative description of high-impact activities” (USTFCARB, 2018, p. 2). The CIDRAP analysis commissioned by this committee also provided a snapshot of agency accomplishments. But it also relied on progress reports, self-reports, and other sources reviewed by the agencies. Though informative, it is not an entirely objective status report.

As is evident from its previous work, GAO is well positioned to conduct objective independent evaluations of agencies’ successes and failures. These reviews might be made more manageable by focusing each biennial review on two or three goals and the activities undertaken across agencies to achieve those goals. GAO could also invite input from nongovernmental organizations, private industry, and professional societies to provide a more complete picture of progress across all organizations involved in the action plans.

Even an independent review can only look at progress against stated goals. A reliance on process outcomes (things like creating a databases, meeting with other agencies) makes it easier to claim successes. Meeting process milestones will not necessarily translate into meaningful improvements in antimicrobial use or the spread of resistant pathogens. There are many influences on the burden of resistant infections in health, and inferring the casual relationship between health policy and health outcomes is difficult. Establishing causality might be an ambitious goal, but more attention to data describing the association between public policy and the burden of antimicrobial resistance would be helpful.

As part of the evaluation envisioned in this recommendation, implementing agencies could give some attention to defining outcome measures and concrete indicators of progress against the goals of the national strategy, not just the steps outlined in the action plan. This may also be a role for the President’s Advisory Council on Combating Antibiotic-Resistant Bacteria. In its recommendations to the secretary of health the advisory council

might be able to identify indicators that better reflect the relationships between the agencies’ work and progress against antimicrobial resistance.

The committee also recognizes that agencies’ priorities can change. Antimicrobial resistance is a dynamic problem, and it could be helpful to have a system in place to help agencies adjust to changes in the disease burden or to benefit from new technologies. One tool that Congress has used to facilitate course corrections on complex government programs is annual reporting on certain programs designated as high risk (GAO, 2021). Programs with a high-risk designation, such as federal oversight of food safety and medical products, have a higher visibility to Congress and to the heads of the agencies involved (GAO, 2000, 2021). This higher level of oversight can translate into greater support and resources directed to the agencies’ needs. Risks to public health and safety are candidates for high-risk designation, as is the assessment of “agencies’ management functions to determine how they contributed to program performance” (GAO, 2000). Both these criteria apply to the CARB program. Adding federal action against antimicrobial resistance to the GAO High Risk List might bring welcome attention to the topic. Such attention could be especially helpful in the face of uncertainty regarding how the COVID-19 pandemic will influence the emergence and prevalence of resistant pathogens (Knight et al., 2021; Rawson et al., 2020). Depending on how this relationship unfolds, it could be important to update national policies aimed at mitigating antimicrobial resistance (Rawson et al., 2020).

REFERENCES