Food Safety Magazine, February/March 2012

Antibiotics are given to food animals for many reasons, such as for infectious diseasetreatment and control, and for disease prevention before a herd- or flock-wideoutbreak of disease occurs. During the 1950s, antimicrobial use for growth promotionwas widely advocated. The practice enhanced the feed-to-weight ratio for poultry,swine and beef cattle. This buoyed the economic incentive for using subtherapeuticquantities of the antibiotics tetracycline and penicillin in dosages from a tenth to ahundredth of a therapeutic dose, and the use of antibiotics in food animal productionfor feed efficiency took root.A Tale of Two AntibioticsIn August 1977, the U.S. Food and Drug Administration (FDA) examined new evidenceshowing that subtherapeutic use is not safe for humans, and FDA proposed towithdraw approval for all use of penicillin in animal feed. That same year in October,evidence surfaced that subtherapeutic use“The emergence ofantibiotic-resistantfoodborne pathogens isinherently linked to howantibiotics have beenused in food animalproduction.”of tetracycline in animal feed is not safefor humans, and FDA proposed to withdrawits approval as well.Much of this thinking may have beensparked by a study published in the NewEngland Journal of Medicine by Levy et al. in1976: “Changes in the intestinal flora offarm personnel after introduction of atetracycline-supplemented food on afarm.” 3 This study tested isolates fromchickens and people on a farm and foundlow initial levels of tetracycline-resistant intestinalbacteria. As expected under thepremise of selective pressure, within 2weeks after the chickens were fed tetracycline-supplementedfeed, 90 percent of thechickens were excreting tetracycline-resistantbacteria. Yet the problem wasn’t isolated to tetracycline; many of the bacteria developedresistance to four antibiotics despite their exposure to tetracycline only.Within 6 months of the administration of tetracycline-spiked feed to chickens, a majorityof the people from the farm were excreting antibiotic-resistant bacteria as well.Significantly, when these same persons were tested 6 months after the tetracycline-supplementedfeed was discontinued, no detectable tetracycline-resistant organisms werefound in the majority of the farm participants. This study showed that the resistantbacteria contained transferable plasmids that conferred multiple antibiotic resistances,not just resistance to tetracycline. The evolutionary pressure imposed by the tetracycline-supplementedfeed for multiple drug resistance in chickens extended to humansin contact with the chickens and the feed, but luckily not in statistically significantamounts to their neighbors. (Comparatively, 7 of 11 farm residents compared withonly 3 of 24 neighbors, p < 0.01, during the 5- to 6-month feeding period showedfecal samples with greater than 80% tetracycline-resistant coliforms.)The 1977 Bureau of Veterinary Medicine (today’s equivalent of the Center for VeterinaryMedicine—CVM—of FDA) concluded that growth-promotion uses of penicillinand tetracycline (two human medicines) in animal agriculture cause theemergence of resistant strains of bacteria, which can move from agriculture onto thedinner plates of the American public through contaminated food, and thus threatenthe health of the general population. For those reasons, they sought, through two Noticesof Opportunity for a Hearing (NOOH) published in the Federal Register, to revokeapprovals for penicillin and tetracycline. 4 This serves to underline the fact thatFDA has consistently believed, for several decades now, that there are human healthrisks in using subtherapeutic doses of medically important antibiotics in animalagriculture.Let’s now jump to December 22,2011, when FDA withdrew the two 1977NOOHs to reverse its approval to administerpenicillin and tetracycline infeed. 5 Instead, FDA stated that they areclosing the dockets because they are engagingin other ongoing regulatorystrategies developed since the publicationof the 1977 NOOHs to address microbialfood safety issues.Although not explicitly stated, thisleads one to the conclusion that FDA isturning to the food animal agriculturalindustry to enforce judicious use itself,and asking that forthcoming voluntaryguidance 209 and its companion document213 be followed.The FDA states in its recent decisionthat it “intends to focus its efforts fornow on the potential for voluntary reformand the promotion of the judicioususe of antimicrobials in the interest ofpublic health. Importantly, this strategyleaves open the possibility of pursuingwithdrawal proceedings at a later time ifFDA’s proposed strategy does not yieldsatisfactory results.” 5Reading Tea LeavesSo what does the future look like?Based on the timeline provided (see “ATimeline of Antibiotic Regulation,” p.40), anything is possible. What can be ascertainedis that using medically importantantimicrobial drugs to increaseproduction in food animals is not consideredby FDA to be judicious use.Guidance 209 has not been formally issued.However, according to 209, theDraft Guidance “The Judicious Use ofMedically Important AntimicrobialDrugs in Food-Producing Animals” givesvast insight into what can be expected.FDA defines judicious use as “using an antimicrobialdrug only when necessaryand appropriate.” The effects of medicallyimportant antibiotics used asgrowth promoters in food animals andtheir effects on increasing antibiotic resistanceare clear, and FDA makes somestrong statements in the guidance draftto tackle this practice.“Antimicrobial drugs that are importantfor treating infectious diseases inpeople, particularly infections caused bybacteria” are considered the working def-38 F O O D S A F E T Y M A G A Z I N E