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Proactive Efforts by U.S. Federal Agencies Enable Early Detection of New Antibiotic Resistance

Posted by David J. Smith, M.D., Deputy Assistant Secretary of Defense for Health Readiness Policy and Oversight, Cathie Woteki, Ph. D., USDA Under Secretary for Research, Education & Economics; Beth P. Bell, MD MPH, Director of CDC’s National Center for Emerging a in Research and Science
May 26, 2016

Just over a year ago, President Obama released a National Action Plan for Combating Antibiotic Resistant Bacteria. As part of that plan, he also charged the Department of Defense (DoD), Department of Agriculture (USDA) and Department of Health and Human Services (HHS) with co-chairing a Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (Advisory Council). In the past year, our three agencies and the Council have held numerous stakeholder meetings, made new discoveries, and undertaken new research to preserve the effectiveness of antibiotics.

In recent weeks, our three agencies have made some important discoveries regarding antibiotic resistance in the United States. Earlier this week, the Department of Defense notified stakeholders that its Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Institute of Research had identified the first colistin-resistant mcr-1 E. coli in a person in the United States. A USDA and HHS search for colistin-resistant bacteria in food animals, retail meats and people also has found colistin-resistant E. coli in a single sample from a pig intestine.

These discoveries are of concern because colistin is used as a last-resort drug to treat patients with multi-drug resistant infections. Finding colistin-resistant bacteria in the United States is important, as it was only last November that scientists in China first reported that the mcr-1 gene in bacteria confers colistin resistance. Following the revelation in China, scientists across the globe began searching for other bacteria containing the mcr-1 gene, and the bacteria have since been discovered in Europe and Canada. The mcr-1 gene exists on a plasmid, a small piece of DNA that is not a part of a bacterium’s chromosome. Plasmids are capable of moving from one bacterium to another, spreading antibiotic resistance between bacterial species.

The patient with colistin-resistant E. coli was treated in an outpatient military treatment facility in Pennsylvania.  Biologic samples were sent to the Walter Reed National Military Medical Center for initial testing and then to MRSN for genetic sequencing to identify the mcr-1 gene.

Our three departments take the emergence of this resistance gene very seriously.  A coordinated public health response is underway to try to prevent its spread.

For example, to respond to the DoD finding of mcr-1 in a human isolate, HHS’s Centers for Disease Control and Prevention is working with DoD, the Pennsylvania Department of Health, local health departments, and others to identify close contacts, including household and healthcare contacts, of the Pennsylvania patient to determine whether any of them may have been at risk for transmission of the bacteria containing the mcr-1 gene. Similarly, USDA is conducting traceback work to determine the sampled pig's farm of origin.

At the same time, the National Antimicrobial Resistance Monitoring System (NARMS) is continuing its search for evidence of colistin-resistant bacteria in the United States. For the past 20 years, NARMS has detected emerging resistance to clinically important antibiotics. NARMS is a partnership between HHS and USDA, as well as state and local public health departments, dedicated to tracking changes in the antimicrobial susceptibility of intestinal bacteria found in ill people, in retail meats, and in food animals.

After the detections in China, the NARMS teams began a two-pronged approach to search for evidence of colistin-resistant bacteria caused by mcr-1 in the United States.  First, USDA’s Agricultural Research Service (ARS) scientists took on a proactive study that used a modified technique to look for bacteria with the mcr-1 gene, employing a targeted and extremely sensitive method to examine whole bacterial populations found in intestinal samples from food-producing animals.  In the still-ongoing study, USDA scientists analyzed the samples by first exposing them to colistin at a concentration that would kill sensitive bacteria and allow any bacteria carrying mcr-1 to survive.  Out of 949 animal samples screened so far, one strain of colistin-resistant E. coli was found in a pig intestinal sample. The DNA sequence of this isolate revealed that the strain contained the mcr-1 gene on a plasmid.  The scientists also determined that the mcr-1 carrying colistin-resistant E. coli is resistant to other antibiotics including ampicillin, streptomycin, sulfisoxazole, and tetracycline.

Second, HHS’ Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration used whole genome sequencing technology to search for the gene in Salmonella, E. coli and Klebsiella taken from human and retail meat sources. As of April 2016, more than 44,000 Salmonella and 9,000 E. coli/Shigella isolates from NARMS as well as the National Center for Biotechnology Information genomic database did not show the presence of the mcr-1 gene.

Although the findings suggest that mcr-1-mediated colistin resistance might be rare, HHS and USDA remind consumers that cooking all meat, poultry and fish to its proper internal temperature kills bacteria, viruses and other foodborne pathogens, whether or not they are antibiotic-resistant.

The NARMS partners will continue to study the newly isolated E. coli strain to better understand mcr-1 gene, as well as continue to analyze the remaining food animal samples for the presence of colistin resistance.  Once USDA’s ARS completes this study, the findings could help determine any additional steps necessary to further understand the mechanisms and dissemination of mcr-1 and associated genes.

Beginning in fall 2016, CDC’s Antibiotic Resistance lab network will provide the infrastructure and lab capacity for seven to eight regional labs, and labs in all states and seven major cities/territories, to detect and respond to resistant organisms recovered from human samples. State labs will be able to detect new forms of antibiotic resistance—including mutations that allow bacteria to survive the effects of the last-resort drugs like colistin—and report these findings to CDC in near real-time.  With this comprehensive lab capacity, state health labs and regional labs that are part of the network will be able to investigate emerging resistance in ways currently unavailable, generating better data for stronger infection control among patients to prevent and combat future resistance threats.

And consistent with the National Action Plan for Combating Antibiotic Resistant Bacteria, CDC, FDA, USDA, DOD and other government agencies will continue efforts to track, slow and respond to the emergence of antibiotic resistance.

The two detections of the mcr-1 gene in the U.S. provide a new clue into the antibiotic resistance landscape, and it also highlights how much we still do not understand. Colistin is rarely used in human medicine compared to other antibiotics.  It is often used to treat multi-drug resistant infections and its use is increasing.  It is not used in animals in this country.  As such, the new detection underscores the urgent need for more research in this area, and that’s why the President’s 2017 budget request also calls for Congress to fund the Agriculture and Food Research Initiative at its full level, allowing our nation’s best and brightest scientists to help the NARMS partners get ahead of the fight to keep antibiotics effective and available. Earlier this month, USDA announced that it is seeking applications for $6 million in research funding to address antibiotic resistance through this program, but currently USDA must leave nine in ten applications for AFRI grants unfunded, keeping meaningful projects off the table.

Category/Topic: Research and Science