[Foodborne Pathogens] The Controversy Over Antimicrobials

It is a difficult – and controversial – issue. On the one hand, antimicrobials (or antibiotic drugs) help control, prevent and treat infectious bacterial disease in food animals, as well as help increase feed efficiency. On the other hand, an undesired consequence of this use is the potential development of antimicrobial-resistant foodborne pathogens.

The issue, though, is not new or U.S.-specific. "The Copenhagen Recommendation," the conclusion to a 1998 European Union Conference on The Microbial Threat, stated that resistance to antimicrobial agents is a major public health problem around the world, and noted: "There is an established but complex relation between the consumption of antimicrobial agents and the prevalence of drug resistance in microorganisms. Dissemination of resistant microorganisms occurs both in hospital and the community. The major route of transmission of resistant microorganisms from animals to man is through the food chain." (Institut National de la Recherche Agronomique)

Accepted use of the antimicrobials was not as conclusive, however. While a basic good practice was defined for treatment for infections, there was not complete agreement on their use for growth promotion, with some participants believing it was essential to systematically replace growth-promoting antimicrobials with non-antimicrobial alternatives, while others argued that this should not be undertaken until a full risk assessment was made. (Full text of this conclusion is available at www.tours.inra.fr/urbase/internet/resultats/antibioresistance/copen2.htm)

While there is general agreement that antimicrobial resistance is a global problem, it remains a divisive topic among food processing professionals. "It is totally controversial," says Bruce Ritter, president of Elisa Technologies, Inc., Gainesville, Fla. "Resistance is a real thing. It is increasing. But how can they keep the animals healthy without using them [the antibiotics]?" The opening paragraph of the Food Safety page of Elisa’s website further defines the controversy: "Since their discovery in the 1930’s antibiotics have treated and saved the lives of millions of people and livestock. However, the wide use of cheap and misused antibiotics in the livestock industry puts high pressure and concerns on human health and bacterial resistance."

The National Antimicrobial ResistanceMonitoring System (NARMS) also agrees that bacterial antimicrobial resistance has become a serious, global problem; and adds that it is a problem which is continuing to increase "due to the frequency with which new emerging resistance phenotypes are occurring among many bacterial pathogens." NARMS is a U.S. surveillance program developed in 1996 to monitor changes in susceptibility of select foodborne bacteria to antimicrobial agents of human and veterinary importance. (For more information, see What is NARMS?)

Antimicrobial resistance is best described as when "bacteria change in a way that reduces or eliminates the effectiveness of antimicrobials to cure or prevent infection," says NARMS Director Dr. David White. Resistance has been described in every major bacterial pathogen, with many strains exhibiting resistance to multiple compounds, he adds, and it is now apparent that any susceptible bacterial pathogen may develop or acquire resistance.

Ritter provided an example which he heard from a professor during his pharmaceutical-school years. You are standing at one goal line of a football field with "organisms" at the other end. The organisms begin to run at you, while you attempt to shoot them down with a machine gun. Those which make it all the way to your goal line without being knocked down have proven to be the fastest, strongest, the most "resistant" to your efforts, and these are the ones which will live to reproduce – passing the traits along to their offspring. It is survival of the fittest, but Ritter says, "Natural selection – as described by Darwin – is altered when we interfere. The antibiotics create an uneven playing field in which the natural bacterial flora cannot compete with the resistant strains."

"Resistance, across the board, is a huge concern because infections caused by resistant bacteria have been shown to be more frequently associated with increased morbidity and mortality than those caused by susceptible pathogens," White explains. In addition, the resistant strains are continuing to evolve, but new antibiotics are not being developed as quickly as in the past. This is of particular concern, because, White says, "There is not a single antibiotic currently available for clinical use in human and veterinary medicine where resistance has not been reported in one bacterium or another."

"That’s why we need prudent and judicious use of antimicrobials in both human and veterinary medicine," he adds. "We need to successfully manage what we have." In fact, the ultimate goal of NARMS is to prolong the lifespan of approved drugs by promoting prudent and judicious use. Thus, White explains, the program’s goal is that of proactive monitoring and research, seeking out "red flags" in order to be able to intervene and take action, before public health can be potentially negatively affected.

How does this impact the food processor? "It’s there," White says, "coming in on the food animals at slaughter." And "it" is not just the known pathogens, such as Salmonella or Campylobacter, rather non-pathogens, such as generic E. coli, can harbor antibiotic-resistance genes and can be transferred to humans via ingestion of contaminated food and/or water.

A 2004 review, "Antimicrobial Resistance Among Gram-Negative Foodborne Bacterial Pathogens Associated with Foods of Animal Origin" by White, et al., stated that antimicrobial-resistant foodborne pathogens are acquired primarily through consumption of contaminated food of animal origin or water, noting, "While there is much disagreement on the health burden imposed by resistance in foodborne bacterial pathogens, it is generally agreed that the use of antimicrobials, whether for growth promotion, prevention, or treatment, can select for resistant bacterial pathogens, and that these pathogens can be transmitted on food originating from sites processing treated animals."

A key activity of NARMS is the collection of bacterial isolates from human and animal clinical specimens, healthy farm animals and raw product from food animals, with the recent addition of retail meats. Through analysis of the samples, NARMS seeks to track the trends of antimicrobial susceptibility in intestinal bacteria from food animals and foods derived from them, facilitate the identification of antimicrobial drug resistance, and educate professionals on emerging patterns of resistance.

Another critical public health initiative is PulseNet, a national network of laboratories, coordinated by the CDC, to perform standardized molecular subtyping ("DNA fingerprinting") of foodborne-disease-causing bacteria using a technique called pulsed-field gel electrophoresis (PFGE). PFGE can be used to distinguish strains of organisms such as Escherichia coli O157:H7, Salmonella, Shigella, Listeria, or Campylobacter at the DNA level, and facilitates early identification of common source outbreaks.

The goal is to "see what’s getting through," White explains, to trace the resistant pathogen from farm animal to slaughter to manufacturing and processing, and ultimately to the consumer. Resistant bacteria from the intestines of food animals may be transferred to retail meat products resulting from fecal contamination during various stages of the slaughter process (e.g., evisceration) and subsequent handling of animal tissue, potentially leading to illness. However, White said, "at times it is difficult to definitely prove this happened." Thus, because retail meats represent a point of exposure close to the consumer, monitoring the prevalence of antimicrobial resistance among foodborne pathogens from such commodities is particularly important to public health surveillance. In addition, White says, "the integration of the antimicrobial susceptibility data (NARMS) with the molecular subtyping analysis (PulseNet) will help identify emerging resistance phenotypes and pathogenic clones being transmitted through the food production system."

Ritter, who was a cattle rancher himself, understands the plight of the meat producer. "You want to generate a large volume of animal product and if you don’t use antimicrobials you lose a lot," he says. "The reality is that you have all your expenses tied up in it and every animal that dies is 100% profit lost." Some of the problems with antibiotics are caused when producers give drugs to the animals beyond the regulated time-before-slaughter cut off or stretch antimicrobials beyond accepted use, such as using a drug designated for a certain animal on a different animal.

Fighting Back. Despite the controversies and known resistance, it is generally agreed that there is a need for and value in the use of antimicrobials for food animals. But there are also best practices and controls which can and should be implemented to protect our food supply. A few of these are:

• Intervention points. There are various intervention points along the food chain where closer monitoring could help fight the evolution of resistance, Ritter says, including:

• on the farm: use of antibiotics not intended for that animal

• at slaughter: time to slaughter from last use of antibiotics, and level of monitoring of such areas as allowed vs. banned products

• during manufacturing: application of HACCP principles

• finished product: increased monitoring.

On the whole, more testing is conducted on exports than on domestic goods, he explains. This is primarily because many other countries have testing regulations, whereas much of it in the U.S. is consumer driven.

• HACCP. The fact that antimicrobials used by meat growers and producers are meeting with resistance means that, despite best efforts, pathogens are creeping up the food chain and entering manufacturing plants. This then makes HACCP efforts in the food that much more important, White says.

• Technology. Ionic silver is one of the newer technologies being used to fight back against foodborne pathogens. Though the use of silver as an antimicrobial dates back to the Egyptians, and the silver-based antimicrobial agent AgIONTM has been approved by FDA, USDA and EPA, it is still evolving and gaining recognition in the food-processing industry for food and water contact. "Silver eliminates bacteria quickly in three ways; it bursts cell walls, stops RNA replication and stops it from metabolizing," says Scott Ferrozzo, president and CEO of BioGuard Plastics in St. Paul, Minn. Bioguard products are imbedded with the antimicrobial agent AgIOn™ which is activated upon touch, and because silver affects three vital functions in the cells, bacteria does not develop a resistance to it. The silver microbial knocks down pathogens every 20 minutes, Ferrozzo says, providing one more layer of protection against the growth or build-up of pathogens.

"The chain of safety is only as strong as the weakest link," Ferrozzo says. But each layer of protection that is added, such as the use of resistance-free silver antimicrobial, helps to decrease the chances of bacterial colonization and cross-contamination.

The most important thing for people to understand about bacteria and pathogens – and reducing the burden of foodborne illness, White says, is the importance of following safe food-preparation, handling and consumption practices, including further implementation of HACCP programs at processing plants.

In addition, Ritter says, "Data is everything." Plants should monitor all incoming products and refuse anything that is not up to quality standards. It is difficult, however, to monitor for everything, he says. "The reality is it’s kind of like the Mexican border. There’s a limit to what can realistically be done." QA

The author is a contributing editor to QA magazine.