The Antibiotic-Probiotic Dance: Role in Food Safety Dr. Rick A. Phillips, D.V.M., M.A.M, Diplomate ACPV Director, Worldwide Technical Service in the Poultry Business Unit of Schering-Plough Animal Health

What sounded pretty far-fetched only a few years ago is steadily becoming reality for some mainstream poultry companies in the United States; that is, producing healthy, competitively priced chicken without the use of therapeutic and/or sub-therapeutic antibiotics.

The true definition of an antibiotic, according to the Webster dictionary, is åsubstances or semi-synthetic substances derived from a microorganism and able, in dilute solution, to inhibit or kill another microorganism.' Unfortunately in the poultry industry this definition includes not only familiar antibiotics like fluoroquinolones, tetracyclines, bacitracins, virginiamycin, tylosin, and lincomycin, but it also includes ionophore anticoccidials.

The movement towards antibiotic-free production began in the European Union. The European community banned the use of feed-grade antibiotics, including bacitracin and virginiamycin in July 1999. They did not extend the ban to include ionophore anticoccidials. However, in the U.S., the USDA has extended the ban to include ionophores in order for companies to label their products úgrown without the use of antibioticsî.

Smaller U.S. producers serving niche or specialty markets were the first to tap into this expanding market, using the value-added benefits of their únatural chickenî to lure health-conscious consumers who are willing to pay a premium for drug-free birds.

To help fill this expanding market, the larger mainstream poultry integrators are starting to follow suit and, in some cases, have actually launched úantibiotic-freeî product lines under separate brand names.

There is even a major shift at this time in the larger poultry integrators' conventional programs to wean themselves from antibiotics before regulators force the issue.

For example, in 1995, a sub-therapeutic antibiotic was used in starter, grower, and withdrawal feeds by 94.3, 98.2, and 75.1% of U.S. broiler production units, but by the year 2000, antibiotic use had declined to 64.8, 66.9, and 48.1% respectively. (1) According to Yvonne Thaxton, executive editor of Poultry ì a magazine serving the packing and food-processing industries, the recent announcements by Tyson Foods, Foster Farms and Perdue Farms that they would eliminate use of some types of antibiotics will likely accelerate the movement toward more drug-free poultry.

Antibiotic use in poultry production in the U.S. is divided into two main categories: therapeutic - used for disease treatment and sub-therapeutic - used for growth enhancement via disease prevention. The major therapeutic antibiotics include but are not limited to the fluoroquinolones, the tetracyclines, neomycin, bacitracin, and the poteniated sulfas.

Three major aspects of grow-out must be considered in operations that remove antibiotics as well as ionophore anticoccidials: 1. Intestinal diseases such as necrotic enteritis and coccidiosis 2. Food Safety with respect to increase in pathogen load in the processing plant, 3. Performance cost due to performance loss.

The major disease in poultry production today that usually requires therapeutic treatment is secondary E.coli infections of the lower respiratory tract, and the most effective antimicrobial currently on the market for the treatment of secondary respiratory E. coli infections is enrofloxacin, a fluoroquinolone antibiotic. The other antibiotic products have lost most of their efficacy with respect to this particular disease.

Unfortunately, The Food and Drug Administration's Center for Veterinary Medicine is proposing to withdraw approval of the animal drug application (NADA) for use of the fluoroquinolone antimicrobial enrofloxacin in poultry. This action is based on the Center's determination that the use of fluoroquinolones in poultry causes the development of fluoroquinolone-resistant Campylobacter in poultry, and that fluoroquinolone-resistant Campylobacter infections are a hazard to human health. With the very high cost of getting an antibiotic to market, only a few, if any, new antibiotic will be produced in the near future to address these disease issues.

The bacterial disease that occurs most frequently with the removal of sub-therapeutic antibiotics is necrotic enteritis. Necrotic enteritis, an enterotoxemic disease of poultry caused by Clostridium perfringens, leads to the development of necrotic lesions in the gut wall as well as increased mortality. (2) The bacitracin antimicrobials are more commonly used to treat this disease in standard programs. Unfortunately, they are not allowed in antibiotic-free programs. The graph below depicts the mortality pattern in a major U.S. poultry facility that grows birds on both antibiotic-free and conventional programs. The majority of the mortality increase in the antibiotic-free flocks is due to necrotic enteritis beginning around 16-18 days of age.

To help alleviate some of the problems that occur with the removal of antibiotics, poultry companies are putting more emphasis on probiotic/competitive exclusion products, water acidifiers, and litter treatments as well as natural biological products such as live coccidial vaccines.

Probiotics and/or competitive exclusion (CE) products are terms that describe the protective effect of the natural or native bacterial flora of the intestine in preventing or limiting the colonization of bacterial pathogens. The natural gut microflora of animals function to break down ingested food, produce some vitamins, and most of all, to provide a natural barrier to pathogenic bacteria. Although the composition of the gut microflora is fairly constant for each poultry species, it can be dramatically affected by various factors such as age of bird, diet composition, environmental conditions, medication, and certain disease conditions.

The first probiotic/CE products were simply fecal contents from healthy adult chickens that were placed in the crop of the newly hatched chicks via gavage. Undefined mixtures of intestinal bacteria were later cultured under anaerobic conditions. These products under laboratory conditions were shown to be highly effective. The problem with undefined cultures is that they could be possibility contaminated with an unwanted pathogen. Some researches have developed defined mixtures of bacteria for use as probiotic/CE products. In general, these products have not been very effective because they contain a single or only a few bacterial strains, and the mode of application is poor.

In laboratory studies, the protective microflora is usually applied directly into the crop of the chick via gavage. For commercial application this technique is not practical; therefore, probiotic/CE products have been produced in liquid and lyophilized forms for practical use. In the field, probiotic/CE products have been administered in in ovo, the drinking water, by hatchery spray, within feed slurries, or injected into agar gels for the chicks to eat. Although some of these methods have had some success with some of the products, none of them proved to be 100% effective. This has been a major stumbling block for probiotic/CE products. The ability to get the product to the birds at the appropriate time and dose and to maintain colonization for a significant period of time has been fruitless.

In fact, in a 1993 review article, Stavric and D'Aoust compared defined CE products for prevention of salmonella in poultry. They concluded that the efficacy of either type of product was much more variable in the field than in the laboratory tests, and overall, undefined CE products were more efficacious than defined culture products.

Maintaining production cost is another major factor in operations that have removed antibiotics from their programs. Listed in the table below is a live production cost comparison from a major U.S. poultry producer currently producing both antibiotic-free and conventionally feed birds. This operation replaced the sub-therapeutic antibiotics with probiotic/CE products in the hatchery as well as the field.

As observed in the chart above, probiotics/CE are not a direct substitute for sub-therapeutic antibiotics at this time. On paper, the probiotic/CE products look very attractive, but in reality they are still in the infancy stage. Operations in the U.S. are taking more of a holistic approach to this problem. Management changes have been made to reduce the level of stress on the antibiotic-free flocks, and live coccidial vaccines are being used very effectively with some of the other prophylactic natural products listed above to improve overall flock performance. As the market sector in this area continues to grow annually, so will the new natural products to help relieve these unwanted effects.

Still, a number of important questions remain. One is whether the demand for antibiotic-free poultry is a growing trend or just a passing fad. Another is exactly how much growers can rely on vaccines and good housekeeping practices alone to keep their flocks healthy without the use of antibiotics. And the big question is: What sort of profits can growers reap-over the long-term as well as the sort-term from raising antibiotic-free chickens?

1. Chapman, H.D. and Johnson Z.B. Use of Antibiotics and Roxarsone in Broiler chickens in the USA: Analysis for the Years 1995 to 2000. 2002 Poultry Science 81:356-364.

2. Paulus, C., and J.P. Ruckebusch. Necrotic enteritis (NE). Zootecnica Int. 19:40-42. 1996.