FDA Was Right to Deny Petition to Restrict Animal Antibiotics

I didn’t have a chance to write about it then, but a few weeks back the Food and Drug Administration denied a citizen petition submitted by environmental activists asking the agency to forbid the “sub-therapeutic” use of certain antibiotics in food animals. The petition — initially filed in 2005, and fundamentally identical to one submitted in 1999 and rejected in 2001 — argued that using antibiotics for growth promotion, rather than to treat infected animals, contributes to the development of antibiotic-resistant bacteria that threaten human health.

The issue is a complicated one, with serious implications for medical treatment and consumer well-being more broadly. We know that development by human pathogens of resistance to medically important antibiotics poses serious public health concerns. And, although a clear link between animal antibiotics use and human disease has not been proven, there are good theoretical reasons to believe, and some real world evidence suggesting, that it does — or at least could — occur.

Nevertheless, I would still argue that FDA made the right call, but for an incomplete reason. In response to both the 1999 and 2005 petitions, the agency essentially said that going through the formal legal process to revoke the approvals for a drug is intensive, time consuming, and a poor use of FDA resources. And because the agency already monitors the development of resistance and has both nominally voluntary and explicitly mandatory programs in place to restrict uses that may pose realistic threats to human health, FDA argued that beginning the revocation process isn’t worth it.

I would further argue, though, that the agency simply does not have sufficient information on which to base a decision to revoke the approvals in question, but that it should begin a less formal investigation to shed some light on the matter. The agency has never before compared the risks that arise from animal antibiotics uses to those that would arise from restricting them. But doing so should be mandatory before any bans or further restrictions are put in place.

The use of antibiotics in animals is only one factor (and a small one at that) in the emergence of antibiotic-resistant pathogens, and it contributes far less to the development of resistance than does misuse among human patients. More importantly, though, the use of antimicrobial drugs in food-producing animals delivers substantial benefits for both animal and human health. Even the often criticized sub-therapeutic uses of these drugs contribute to reduced pathogen loads in animal-derived foods and have a positive impact on human safety. The question that few have even bothered to ask, and that the scientific community has not yet answered is whether, on balance, forbidding sub-therapeutic use of antibiotics in livestock would do more good than harm. There is good, though by no means conclusive, reason to believe the answer is no.

Generally, even when antibiotic-resistant bacteria are present in livestock, the likelihood of human exposure is remote, in part because risk management strategies to minimize and contain resistant pathogens have been implemented throughout the food chain. But, even when human consumers are exposed to resistant bacteria, the effect of the drug-resistance is typically inconsequential. General intestinal enteritis caused by Salmonella, for example, is rarely treated with antibiotics, leaving little opportunity for a therapeutic failure. And, in other cases where antibiotic treatment is indicated, bacteria that are resistant to one or more antibiotics remain sensitive to others. While not zero, the risk of a treatment failure in human patients arising from the development of antibiotic-resistant pathogens in food animals is quite low (See here, here, here, and here).

But is it worth tolerating even a small risk merely for the benefit of cheaper food? Some would argue “no.” The New York Times, for example, editorialized that rejecting the petitions was “a bad decision that runs counter to the F.D.A.’s own research.” And “The drugs make the animals grow faster, but their overuse increases the likelihood of antibiotic-resistant pathogens.” But posing the question that way ignores other important benefits.

Consumers benefit from lower prices, to be sure. But humans also derive health benefits from the presence of safer and healthier livestock animals. Sub-therapeutic antibiotics use helps to control and reduce the spread of a number of zoonotic diseases, and it is associated with a generalized reduction in health problems in the animals in which they are used. Carcasses from slaughtered animals not treated with antibiotics are more likely to be contaminated with human pathogenic microorganisms than those from treated animals (See here and here). And, because sub-therapeutic antibiotics use increases feed conversion efficiency, it lets farmers produce more food with fewer animals and less feed, which has significant environmental benefits — including, but not limited to, a need for less land in raising livestock and animal feed crops, and less waste from the animals.

Furthermore, experience in foreign countries that have banned or heavily restricted sub-therapeutic use is decidedly mixed. So, it is not clear whether a ban in the U.S. would result in less resistant bacteria or improved human health outcomes. Denmark, for example, began restricting sub-therapeutic uses in 1995. But over the following decade, while resistance to some antibiotics decreased among some pathogens in some livestock animal species, resistance among other pathogens to other antibiotics in other animals rose (See here and here). And there is little evidence that the occurrence of antibiotic-resistant pathogens in humans was affected at all.

Similar results were seen following the European Union-wide restriction on sub-therapeutic uses. “The expected decrease in the incidence of resistant human pathogens did not occur. Instead, prevalence of many resistant human pathogens increased, in some cases up to 49 percent of the pre-ban incidence.

There is no doubt that the rise in antibiotic resistant bacteria is a serious problem. And it may even be wise to ban the use of new antibiotic classes — or existing classes that are considered antibiotics of last resort — in livestock, or at least to postpone their use for a period of years following their introduction. But it’s not remotely clear that consumers would experience net positive benefits from a ban on essentially all sub-therapeutic uses.