Conclusions

Antimicrobials are important tools that are integral to our complex food system. Antimicrobials (e.g., antibiotics and other substances that act against microorganisms) provide for high quality or good physical condition of crops and good health of food animals entering the food chain.

Antibiotics are used to treat, prevent, and control disease among food animals and in some cases to improve feed utilization and, thus, growth rate. Nonantibiotic antimicrobial agents enable disinfection or sanitization of animal production premises, transport equipment, carcasses, slaughter facility equipment, and effective sanitation during food processing, and ensure food quality and safety.

The availability of antibiotics to treat infectious diseases has radically improved human and animal well-being. Paradoxically, this very success threatens their future utility. Both the prudent and inappropriate use of antibiotics in human medicine, veterinary medicine, and animal husbandry create selective pressure that favors the emergence of antibioticresistant microbes. Coupled with specific genetic resistance mechanisms, the selective pressure of antimicrobials may result in foodborne bacteria that are resistant to antimicrobials.

Antibiotic resistance among foodborne pathogens may create an increased burden to human health in different ways, including: (1) resistant pathogens contaminating food animals have the potential to reach humans; (2) human use of antibiotics may increase the risk of acquiring an infection with an antimicrobial resistant pathogen; (3) human infection with a resistant microbe may limit illness treatment options (in the uncommon instances of foodborne illness in which antibiotic use is warranted); and (4) antibiotic-resistant foodborne pathogens may develop increased virulence.

Antibiotic-resistant foodborne pathogens are a subset of foodborne pathogens, any of which may cause illness. Antibiotic-resistant intestinal bacteria may be present in food animals, irregardless of exposure of the animals to an antibiotic. The types of bacteria, their resistance profiles, and prevalence vary from animal to animal and species to species. In spite of the best efforts to prevent or eliminate them, some antibiotic-resistant bacteria contaminate carcasses, as do antibiotic susceptible bacteria. Interventions that effectively reduce the prevalence of foodborne pathogens also reduce the prevalence of those that are resistant to antibiotics.

There are a variety of resistance mechanisms and genes that complicate the antibiotic resistance issue. Commensals, such as nonpathogenic E. coli and Enterococcus spp., may serve as reservoirs of potential antimicrobial-resistance genes in the environment from which resistance may be transferred to other commensals or pathogenic bacteria. However, of singular interest are those antibiotic-resistant intestinal bacteria, such as Salmonella and Campylobacter that can contaminate foods during slaughter or processing and result in human illness. The key points of influence that food scientists have in preventing the spread of antibiotic-resistant and sensitive pathogenic microorganisms in foods are preventing them from entering the food supply, and if present, inactivating them or preventing their growth.

Selective pressure for the development of antimicrobial resistance occurs within all uses of antimicrobials, including use in the food system from production to processing. Resistance among some foodborne bacterial pathogens has increased during the past 15 - 25 years. Increases in resistance have generated heated debate about the appropriate use of antibiotics in agriculture, particularly in food animal production. Although the people involved in the various stages of the food system can influence dissemination of foodborne pathogens, including those resistant to antibiotics, through various intervention strategies, they neither control the development of antibiotic resistance nor human antibiotic use patterns. Given the different resistance mechanisms, conditions selecting for resistance, and dissemination patterns of resistant microorganisms, a single approach to solving the resistance issue is not possible.

Various factors complicate our ability to fully understand the transfer of resistant bacteria through the food chain to human illness causation. These factors include resistance genes unique to the various foodborne pathogens; animal production and distribution prior to slaughter; processing practices; retail food preparation, distribution, and storage; consumer food preparation practices; varying susceptibility to pathogens among different subpopulations; and varying medical practices and treatment options. The extent to which antibiotic use in food animals produces clinically important antibiotic-resistant infections in humans is unknown. Contributing to this problem is the inability to obtain quantitative data about the magnitude of antibiotic use in animal husbandry, subsequent resistance, and impact on human health. Additionally, the economic impact of antibiotic resistance is difficult to assess, as are potential affects on trade.

To address the complexity of resistance selection, transfer through the food chain, and human health consequences, qualitative and quantitative risk assessments are now being applied. For many antibiotics, such as tylosin, tilmicosin, and virginiamycin used in food animals and for which a risk assessment has been conducted, estimated risk to human health is small. Fluoroquinolone use to treat poultry disease through water, however, was deemed by the FDA as an unacceptable risk to humans and its approval was withdrawn. The Food and Drug Administration/Center for Veterinary Medicine now requires new animal drug sponsors to satisfy microbial food safety criteria for antibiotic products by submitting evidence outlined in Guidance 152 that appropriate use conditions are ensured.

Risk management strategies to minimize and contain antibiotic-resistant foodborne bacteria are in place all along the food chain, but can be improved. The strategies that have been implemented include use of various antibiotic alternatives, implementation of judicious or prudent antibiotic use guidelines, and implementation of national resistance monitoring programs.

Although there are concerns with antibiotics entering the animal production environment through manure or other waste streams, more information is needed to better understand the situation to implement effective control strategies. Very little is known about the exposure routes of antimicrobials in the environment and the fate of antimicrobials within ecosystems; environmental impacts are not completely understood. Current evidence suggests that it is not likely that antimicrobials in manure will pose any direct risk to soil microbiota. However, it is not yet possible to exclude other indirect effects on soil microbiota and ecosystems that are driven by changes in the microbial community from the presence of antibiotics. Environmental research is in its infancy, currently able to simply identify whether a hazard exists and is not yet able to measure impact. Although bacteria may be exposed to an antibiotic for an extended period of time, on the farm or in humans, bacterial exposure to food antimicrobials (e.g., sanitizers) generally occurs only once. The prevalence and mechanism of resistance among most food-use antimicrobial compounds is often unknown. When it occurs, resistance to food antimicrobials is of little practical relevance to the food industry because the antimicrobial concentrations used in food manufacturing are well above the low levels to which bacteria exhibit resistance. However, the ability of some sanitizers and disinfectants to induce multiple drug resistance pumps, which also confer antibiotic resistance, is of some concern.

The impact on human health of bacterial pathogen resistance to food antimicrobials is not fully understood. Although some studies have suggested that in certain situations (sublethal use, overuse, biofilms, and cross-resistance mechanisms, for example) the potential for negative impact on public health exists, resistance to food antimicrobials is not considered a major public health concern because the resistance mechanisms are often temporary adaptations. To date, the use in foods of chemical and biological antimicrobials and physical preservation systems has been remarkably successful in providing safe foods and has not been compromised by the occurrence of resistant microorganisms. In addressing quality and safety, traditional and naturally-occurring food antimicrobials are increasingly applied as multiple, synergistic hurdles to inactivate or inhibit growth of spoilage and pathogenic microorganisms. The use of multiple hurdles in food manufacturing is likely to combat resistance to singular food safety interventions.

At present there is little evidence of an impact on human health of use of antibiotics in plant production. Similarly, ingestion of antibiotic-resistant bacteria from aquaculture and contact with animals, including pets, does not appear to comprise a significant threat to human health.

The National Antimicrobial Resistance Monitoring system (NARMS) and FoodNet surveillance data are now beginning to reveal resistance trends. NARMS resistance trends are not consistently in one direction. Trends reported by other surveillance programs during the past 20 - 25 years reveal increasing resistance, while other sources reveal decreasing resistance trends, particularly in the last 6 - 7 years.

It is difficult to correlate antibiotic resistance among foodborne pathogens with particular types of antibiotic use (e.g., therapeutic, growth promotion) on the farm. Increased incidence of illness within a herd or flock, and concomitant therapeutic use of antibiotics in any given year may or may not result in increased use of antibiotics potentially selecting for resistant microorganisms. Therefore, it is difficult to compare year-to-year resistance trend data without correlating the data with disease prevalence and corresponding changes in annual use of a specific antibiotic or class of antibiotics.

The history of the epidemiology of Salmonella shows that clones, including MDR-clones, spread worldwide, and then lost predominance. Some clones of Salmonella Typhimurium DT104, which possess a penta-resistance gene cassette, have spread widely and resulted in foodborne disease outbreaks. It appears that the prevalence of Salmonella Typhimurium DT104 and/or the penta-resistant Salmonella Typhimurium may have peaked in 1996, and declined since then.

There are limited new veterinary drugs in the pipeline. Of drugs under development, many of them are targeted for non-infectious diseases. Although alternatives to antibiotics have been explored, none can replace those used for therapeutic purposes. Thus, maintaining the continued efficacy of currently available antibiotics is critical.

Regulatory targeting of specific antibiotic-resistant foodborne pathogens may not be the most successful or cost effective means to reduce overall foodborne illness. A HACCP approach applied throughout the food chain is considered the most effective measure to controlling foodborne pathogens and thereby reducing foodborne illnesses. Most interventions, critical control points to kill or reduce foodborne pathogens, for example, are equally effective in controlling microbes regardless of their resistance to antibiotics. Thus, applying interventions to control foodborne pathogens in general, rather than focusing on antibiotic- resistant strains specifically, would have the greatest impact in reducing overall foodborne illnesses.