Action Plan — The Focus Areas:
III. Research (Issues A-B)

Antimicrobial resistance is among the most challenging problems in microbiology, clinical medicine, and public health. Antimicrobial resistance is not one problem, but an overarching term for an array of problems inherent in the evolution of microbes and influenced by antimicrobial use. Basic and clinical research provides the fundamental knowledge necessary to develop appropriate responses to antimicrobial resistance emerging and spreading in hospitals, communities, farms, and the food supply. Major scientific accomplishments throughout the years have contributed much to the understanding of the fundamental biological processes of AR within microbes and the resulting impact on humans, animals, and the environment. This knowledge base provides us the opportunity to influence these processes and outcomes.

Because of its broad scope, the U.S. research community has a major contribution to make in meeting the goals the AR Task Force has set forth. The research and development of diagnostic tests, new antimicrobial agents, novel therapeutic products, and vaccines and other preventive approaches in response to AR is a multistep process that begins with basic research discoveries and ends with the availability and use of a new product or implementation of a process. Along this pathway three areas need to be addressed: the identification of gaps and needs in the molecular and cellular understanding of resistance, the infrastructure to support a robust research community, and a means for moving research findings into the development of new products.

The Interagency Task Force has worked with representatives from the public and private sector to identify important research needs in microbial physiology, ecology, genetics and mechanisms of resistance. Existing gaps in knowledge and understanding should be addressed to augment the federal and private sector response to the overall problem. Efforts are underway to build and enhance the field of AR research, through increased focus, recognition, and collaboration. The aim is to develop a research infrastructure to support a critical mass of AR researchers who will interact, exchange information, and stimulate new discoveries. In order to move novel ideas arising in the research laboratory to useful products or approaches, support of the underlying infrastructure to study and test products and a mechanism to transition to industrial partners is necessary.

This effort will involve federal agencies that conduct, support and promote basic and clinical research in academia and industry and will involve prioritizing needs, identifying key opportunities, recruiting new investigators to the field, and making responsible use of resources to address AR problems.

A.	Issue: Specific scientific gaps remain in the understanding of microbial physiology, ecology, genetics and mechanisms of resistance.
	1.	Goal: Identify gaps and address existing research needs and identify new ones.
		a.	Action Items
			67.	Additional research, including high risk and high payoff research in nontraditional fields, is needed to enhance the understanding and assess the impact of:
					Mechanisms of AR emergence, acquisition, spread, persistence, and decline, with special regard to multidrug resistant organisms;
					Emergence and transfer of resistance genes among microorganisms in vivo, including epidemiologic factors;
					Microbial ecology and the role of normal flora as a repository of resistance factors, as well as the use of susceptible bacterial populations in the control of antimicrobial resistance;
					Effects of preventive, therapeutic, growth-promoting agents and residues of agents in the environment on the microbiota of animals, plants, soil, and aquatic environments;
					Host factors and immune modulators (e.g., cytokines) in clinical resistance to treatments for opportunistic infections;
					The determinants of colonization and infection with drug-resistant pathogens; and
					Variations in antimicrobial use patterns that may affect the emergence and spread of resistance and the outcome of treatment, such as:
						Differences in duration and dosage in the administration of antimicrobial agents;
						Prophylactic use of antimicrobial (including antibacterial and antifungal) agents;
						Drug combinations used to treat resistant organisms; and
						The rotation (cycling) of antimicrobial drugs and other similar changes in selection and use of drug classes.
				Coordinator: NIH Collaborators: CDC, FDA, DVA, USDA, EPA, DoD Timeline: Initiated
			68.	Conduct further government-wide assessments with external input on the scope and composition of AR research to identify research opportunities. Coordinators: NIH, CDC, FDA, USDA Collaborators: DoD, DVA, AHRQ, EPA, HCFA Timeline: Initiated
B.	Issue: The existing research infrastructure needs to ensure a critical mass of researchers in AR and related fields.
	1.	Goal: Augment the scientific research infrastructure.
		a.	Action Items
			69.	Work with the appropriate peer review structures to ensure that the requisite expertise is applied to the review process to facilitate funding of quality AR research. Coordinators: NIH, DVA, FDA Timeline: Begin in one to two years
			70.	TOP PRIORITY ACTION ITEM — Provide to the research community genomics and other powerful technologies to identify targets in critical areas for the development of new rapid diagnostics methodologies, novel therapeutics, and interventions to prevent the emergence and spread of resistant pathogens. Examples include tools such as microbial genome sequences, information on comparative genomics, DNA chip technology, informatics, and assistance in the application and use of these tools. Coordinator: NIH Collaborators: DoD, USDA, FDA Timeline: Initiated
			71.	Encourage sharing of AR data between industry and the research community, including genomics and other technologies. Coordinator: NIH Collaborators: DoD, USDA, FDA Timeline: Begin in three to five years
	2.	Goal: Develop a critical mass of researchers in AR.
		a.	Action Items
			72.	Bring new researchers into the field, by utilizing appropriate strategies such as training and research opportunities. Coordinator: NIH Collaborators: CDC, FDA, USDA, DoD, DVA Timeline: Initiated
			73.	Organize conferences that address research issues relating to AR. Coordinator: NIH Collaborators: CDC, USDA, FDA, DVA, DoD, AHRQ Timeline: Initiated

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