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ASM has been asked by the working group to address three questions: The first of these questions asks:

From the perspective of the ASM, what should the U.S. Government be doing to optimize the interactions between the multiple Federal laboratories that support public health in order to address better the continued problem of antimicrobial-resistant bacteria?

A) Modernize Public Health

The U.S. Government should articulate an overarching vision and national strategy for the transformation of public health through the use of modern technologies like NGS, metagenomics, and bioinformatics. This strategy should encompass what the next 5–10 years will look like and include visions for research, public health and clinical practices.

B) Collaborate and Leverage within Agencies and with Colleagues

U.S. Governmental agencies should leverage, rather than duplicate efforts, by collaborating inter-agency as well as with academia and industry to utilize existing technology and bioinformatic resources rather than trying to replicate these services ‘in house’ at each agency. In addition, academic centers, clinical laboratories, and U.S. industry partners may be interested in working with the government to help public health programs in the U.S. and other countries adapt to the threat of antibiotic resistance.

For a specific example, The National Antimicrobial Resistance Monitoring System for Enteric Bacteria (or NARMS) is a collaboration among state and regional PH laboratories, the CDC, the FDA and the USDA that tracks changes in the antimicrobial susceptibility of intestinal bacteria found in humans, meats, and food animals in the U.S. This effort helps to protect the public’s health by providing information about emerging bacterial resistance and the mechanisms by which resistance is spread.

This program could be more effectively leveraged utilizing modern technology and bioinformatics to produce more real time, actionable public health information. These updates are also necessary in order for other U.S. programs involved in antimicrobial resistance to be more effective.

C) Invest in New Technologies and Aid Research

The U.S. Government should keep abreast of new technologies then aid, and fund, not only the development of these assays, but the use of these rapid diagnostics for the identification and characterization of antibiotic-resistance bacteria. Such investment will aid both basic and applied research to find future applications for combating antimicrobial resistance.

The second question asks:What best practices can the ASM suggest in order to fully operationalize the nascent U.S. Government specimen repositories of antimicrobial resistant organisms, for epidemiology, for research, and for the development of clinical/diagnostic countermeasures?

A) Public Health testing of antibiotic-resistant organisms

First, many state PH laboratories do not have the resources in order to provide their clinical laboratories with testing for antibiotic-resistant organisms, therefore this testing is not offered by all state PH laboratories. It should be a priority for the U.S. Government to assure that this testing is done in all state PH laboratories. This will allow for faster detection of resistance in our hospitals, long term care facilities and the public at large. In addition, this will allow the necessary interaction with the states’ epidemiology colleagues to more efficiently track both hospital-acquired infections and antibiotic resistant organisms.

B) Public Health resistant organism datasets

In the fight against antibiotic-resistant organisms, the U.S. Government would also benefit in working toward making bioinformatic analysis datasets available for virulent and antimicrobial resistant organisms. Having these data available for research and industry colleagues could lead to identification of new genetic markers that would in turn help to enrich public health databases.

These datasets are important not only for the human public health but also for environmental and animal health sectors; this would add important and needed information the °®¶¹´«Ã½ States’ contributions to the One Health Concept.

The third question asks: How best to tie in resistant bacteria data derived from the entirety of U.S. human and animal health disease surveillance?

A) Antibiograms

The U.S. Government could help to incentivize the development of ’real time’ national as well as regional/state antibiograms.

• Antibiograms are periodic summaries of antimicrobial susceptibilities of bacterial isolates.
• Antibiograms are often used by clinicians to assess local susceptibility rates, as an aid in selecting empiric antibiotic therapy and in monitoring resistance trends over time within an institution.
• Antibiograms can also be used to compare susceptibility rates across institutions, states, and regions in order to track resistance trends.

These antibiograms would allow for accurate surveillance and rapid detection of antibiotic resistant organisms to help identify areas in need of interventions to decrease the spread of these resistant organisms.

B) Unfunded mandates from Public Health to Clinical laboratories

There are national and state laws which require the submission of isolates from clinical laboratories to PH laboratories for surveillance purposes; however, we still have significant shortcomings on the part of individual clinical laboratories complying with these requirements. One recent example is the Listeria outbreak associated with Bluebell ice cream. Failure of clinical laboratories to submit isolates and clinical data is often related to cost associated with this activity. Clinical laboratories are doing more and more with less and less, and as these are the sites where we initially detect antibiotic resistant bacteria in human infections, without clinical laboratories as part of our surveillance plan, we will not have an accurate picture of the magnitude of antibiotic resistant organisms in our country. Support for the software necessary for automating the computer reporting of these organisms from clinical to state PH laboratories is one example of how the U.S. Government could assist with surveillance activities in combating the emergence of antibiotic-resistant organisms.

C) Culture Independent Diagnostic Tests

Adapting public health systems to the increasing use of culture-independent diagnostic tests is an urgent priority. For example, soon many clinical laboratories will stop culturing for enteric pathogens but instead switch to molecular methods for enteropathogen detection. These assays are becoming widely available and preferred due to their rapid and more accurate results over current testing methods. Thus, clinical laboratories will NOT continue to maintain conventional technology alongside this new, more expensive molecular testing. An approach for the U.S. Government to this problem is investing or incentivizing our colleagues in industry so that diagnostic companies will develop new technologies that will allow for sequencing of pathogens (including their antibiotic resistance determinants) directly from positive samples. In this way clinical laboratories will be able to send metadata to public health rather than sending isolates or clinical samples. This would allow for much more efficient detection of outbreaks of resistant organisms leading to more rapid PH investigations in order to better help protect the public.

D) FDA regulated resistance testing

Lastly, many community hospital clinical laboratories continue to use outdated information for determining the presence of antibiotic resistant bacteria. The U.S. Government should instruct the FDA to allow antimicrobial susceptibility manufactures to accept either the FDA or the Clinical Laboratory and Standards Institute (CLSI) breakpoints for these determinations. This would allow more diagnostic laboratories to do appropriate testing to identify multi-drug resistant organisms.

The American Society of °®¶¹´«Ã½ would like to thank you for this opportunity to comment on these important questions concerning our public’s health and antimicrobial resistance.

Thank you.