Antimicrobial resistance is the ability of bacteria and other microorganisms to resist the effects of substances that inhibit their growth or survival. Many factors contribute to the emergence of antimicrobial resistant microorganisms, but the use of antimicrobials in medicine and agriculture is the most important factor. Antimicrobials are commonly used in food animals to prevent, control and treat infections and to promote the growth of food-producing animals. (Recently, FDA has implemented a process to eliminate the use of medically important antibiotics for growth promotion by December 2016). Of particular concern is the potential for pathogens such as Salmonella and Campylobacter, commonly present in the intestines of food producing animals, to develop resistance when exposed to antibiotics given to the animal. This raises the possibility that humans could become infected with these resistant organisms through exposure to infected livestock or contaminated food products.
Increasing antimicrobial resistance has prompted public health and regulatory officials to more closely examine the ways in which antibiotic use in food-producing animals may contribute to resistance in animal and zoonotic bacteria. The World Health Organization (WHO), the Food and Agriculture Organization (FAO) and the World Organization for Animal Health (OIE) have published recommendations that Member States implement monitoring programs for the use of antibiotics in animals, as well as for the occurrence of antibiotic resistance in bacteria from animals and from food of animal origin (AGISAR, 2013).
The National Antimicrobial Resistance Monitoring System
The National Antimicrobial Resistance Monitoring System (NARMS), established in 1996, is a collaborative program of the U.S. Food and Drug Administration (FDA), the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Department of Agriculture (USDA), state and local health departments, and universities. NARMS monitors antimicrobial susceptibility in selected enteric bacteria from humans, retail meats and food-producing animals.
In addition to monitoring antimicrobial susceptibility, NARMS conducts epidemiologic investigations examining risk factors and clinical outcomes of infections with specific bacterial subtypes or subsets of bacteria that exhibit particular resistance patterns. NARMS scientists also perform microbiologic studies to determine the genetic traits conferring antimicrobial resistance and the mechanisms that mediate the transfer of resistance between bacteria. Other studies have been done to improve methods for isolation and typing, and to develop quality control parameters for antimicrobial susceptibility testing methods. Isolates in the NARMS collection also have been examined for relatedness using pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). PFGE patterns are stored in CDC’s PulseNet database or USDA’s VetNet database where they serve as a point of reference for outbreak investigations. WGS data on NARMS isolates are publicly available via the National Institutes of Health NCBI web portal.
- To monitor trends in antimicrobial resistance among enteric bacteria from humans, retail meats, and animals;
- To disseminate timely information on antimicrobial resistance to promote interventions that reduce resistance among foodborne bacteria;
- To conduct research to better understand the emergence, persistence, and spread of antimicrobial resistance; and
- To provide data that assist the FDA in making decisions related to the approval of safe and effective antimicrobial drugs for animals.
The Components of NARMS
The NARMS program has three components, which are briefly described below.
The human component of NARMS was launched in 1996 within the framework of CDC’s Emerging Infections Program and the Foodborne Diseases Active Surveillance Network (FoodNet). Initially, it included non-Typhi Salmonella and Shiga toxin-producing Escherichia coli (STEC) O157 isolates from 14 state and local health departments. In 1999, Salmonella serotype Typhi and Shigella testing was added. By 2003, NARMS conducted nationwide surveillance of Salmonella, Shigella, and E. coli O157 from humans. Testing of Campylobacter from humans began in 5 FoodNet sites in 1997 and expanded to all 10 FoodNet sites by 2003. In 2009, NARMS began testing Vibrio species other than V. cholerae from all 50 states. Antimicrobial susceptibility testing of NARMS human isolates is performed at CDC’s laboratories in the National Center for Emerging and Zoonotic Infectious Diseases in Atlanta, Georgia.
Retail Meat Component
The retail meat component of NARMS was launched in 2002. Retail meat surveillance is conducted through collaboration with 15 state and local departments of public health and 4 universities. Participating sites purchase chicken, ground turkey, ground beef, and pork chops at retail stores and culture them for Salmonella. Retail poultry is also cultured for Campylobacter. A subset of NARMS sites also culture retail meats for E. coli and Enterococcus. Isolates are sent to FDA’s Center for Veterinary Medicine (CVM) Office of Research in Laurel, Maryland for species and serotype confirmation, antimicrobial susceptibility testing, and genetic analysis.
USDA’s Agricultural Research Services (ARS) initiated the animal component of NARMS in 1997 by testing Salmonella isolates recovered by the USDA Food Safety Inspection Services (FSIS) Pathogen Reduction/Hazard Analysis and Critical Control Point (PR/HACCP) verification testing program. Testing later expanded to include Campylobacter (1998), E. coli (2000), and Enterococcus (2003). The NARMS Integrated Report includes HACCP isolate data for Campylobacter from chicken carcass rinsates and data for Salmonella from carcass rinsates (chicken), carcass swabs (turkey, cattle and swine, and ground products (chicken, turkey, and beef). Isolates are recovered from samples obtained at federally inspected slaughter and processing plants. Antimicrobial susceptibility testing for the animal component of NARMS is performed at the USDA laboratories in Athens, Georgia.
In 2013, NARMS began a new animal sampling scheme through USDA’s Food Safety and Inspection Service (FSIS). Cecal samples were collected at the slaughterhouse from individual animals of the major production classes, including young chickens (6-7 weeks of age), young turkeys (18-20 weeks of age), dairy cow, beef cow, steer, and heifer, and swine (market swine, sows). The NARMS Integrated Report includes cecal isolate data for Salmonella, Campylobacter, Escherichia coli, and Enterococcus recovered from these commodities. Isolates were sent to CVM’s Office of Research in Laurel, Maryland for species and serotype confirmation, antimicrobial susceptibility testing, and genetic analysis until December 31, 2013. Beginning in 2014, this work has been conducted at the FSIS Eastern Laboratory in Athens, GA.
Categorization of Antimicrobial Agents
The antimicrobials that NARMS uses are selected based on their importance in human and veterinary medicine and for their utility as epidemiological markers for the movement of resistant organisms and genes between environments. NARMS tests for susceptibility to 15 antimicrobials in Salmonella and E. coli, 9 in Campylobacter, and 16 in Enterococcus.
In its Guidance for Industry entitled ‘Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern’ (GFI #152), FDA provides recommendations on how to rank antimicrobials with their relative importance in human medicine. Antimicrobial agents are categorized based on the following criteria 1) used to treat enteric pathogens that cause foodborne disease, 2) sole therapy or one of few alternative to treat serious human disease or drug is essential component among many antimicrobials in treatment of human disease, 3) used to treat enteric pathogens in non-foodborne disease, 4) no cross resistance within drug class and absence of linked resistance with other drug classes, 5) difficulty in transmitting resistance elements within or across genera and species of organisms. Based on these relevant factors, drugs are ranked as C- Critically Important, H- Highly Important, or I- Important. Following these rankings, resistance patterns are evaluated and reported differently depending on the consequences to public health of individual drug classes.