January 9, 2012

One Step Forward, Two Steps Back: FDA on Cephalosporin, Penicillin, and Tetracycline

Tyler Smith

Tyler Smith

Program Officer, Food Production and Public Health

Johns Hopkins Center for a Livable Future

Last Tuesday, the U.S. Food and Drug Administration (FDA) announced that it will ban the “extra-label” use of cephalosporin antibiotics in food animals—that is, veterinarians will not be permitted to use drugs in this class of antibiotics except in ways approved by FDA.  (A “drug class” refers to a group of drugs that work in similar ways.  Cephalosporins are members of the broad group of beta-lactam antibiotics, which includes penicillin drugs as well.  Beta-lactams kill bacteria in similar ways.) FDA’s announcement came almost two weeks after the agency said it would not restrict the use of the other group of beta-lactams, penicillins, as well as tetracyclines, two other drug classes on which it had contemplated taking action. In the span of just two weeks, then, FDA has moved to prevent misuse of one drug while shirking its responsibility for two others. One step forward, two steps back.

The World Health Organization considers all three of these drug classes “critically important to human medicine.” Cephalosporins have many uses in human medicine, including treatment of serious Salmonella infections in children.  (A fourth drug class, fluoroquinolones, is used to treat adult cases of salmonellosis, or disease resulting from Salmonella infection, but it can have serious adverse effects in children, making the efficacy of cephalosporins essential to treating children with this common foodborne illness.  FDA banned extra-label use of fluorquinolones in food animals, and any use of these drugs in poultry, several years ago over concerns about fluorquinolone resistance.)

FDA’s inaction on penicillins and tetracyclines does not reflect basic scientific knowledge. For example, it makes little sense to restrict the use of cephalosporins but not penicillins, as both are beta-lactams; a drug that selects for bacteria resistant to penicillins can also select for resistance to cephalosporins, and vice versa.  Nevertheless, we support efforts to ensure responsible use of cephalosporins.

Join the Debate: Submit a Comment

The cephalosporin ban will take effect 90 days from last Friday, on April 5, after a 60-day public comment period plus 30 days for FDA to review the comments. A comment period gives members of the public—including public health advocates—an opportunity to comment on the wording of the ban and its likely effect on human and animal health. We encourage members of the public concerned about the misuse of antibiotics in food animal production to submit comments to FDA that express support for the measure.

When the agency proposed a similar ban in 2008, it received about 170 comments—most were from pharmaceutical and agricultural interest groups and veterinarians who opposed the ban as written, while just two comments supported it.  The agency withdrew its proposal that year.  This time around, it is important that the public health community make a strong showing of support.

To help members of the public submit comments, we have prepared a plain-language description of what the ban does.  Unlike the 2008 proposal, which would have prohibited all extra-label use of cephalosporins in food animals, the new ban makes broad exceptions to preserve the ability of veterinarians to treat sick animals and control diseases that occur in herds and flocks.  CLF’s Meghan Davis, a veterinarian and PhD candidate in the Department of Environmental Health Sciences here at the Bloomberg School of Public Health, believes the ban provides the flexibility that veterinarians need to treat sick animals.  We are hopeful that the ban will end the uses of cephalosporins that do the most to promote cephalosporin-resistant infections in humans. (See the flowchart, below, for a graphic representation of the proposed ban.)

Specifically, FDA has proposed the following:

FDA is banning the use of cephalosporin drugs in major species (cattle, swine, and poultry) if those drugs have not been approved for use in food animals.  In doing so, FDA is prohibiting the use of cephalosporin drugs used in human medicine in certain “major species”— cattle, swine, and poultry.  (Humans, cats, and dogs are also major species, but cephalosporin use in these species is unaffected by the ban.)  Because such drugs have only been evaluated for use in humans, little is known about their effects in other species, and FDA has not developed guidelines on how these drugs can be used responsibly in major species.

FDA is banning the use of ceftiofur, one of two cephalosporin drugs approved for use in food animals, for disease prevention in major species. Large quantities of antibiotics are routinely fed to food animals, ostensibly to prevent diseases that tend to result from the unsanitary conditions common at industrial farms, but in reality intended to make animals grow faster. This “prophylactic” use typically involves the continuous administration of small quantities of antibiotics to animals, which is more likely to select for resistant bacteria than the occasional use of larger doses to treat and control animal diseases.  Under the ban, ceftiofur can no longer be used in major species for prevention, only treatment and control of disease. (The difference between prevention and control is murky.  In general, prevention means continuous dosing of animals to avoid any disease, while control refers to dosing a herd or flock with a single course of antibiotics in the event of a known exposure to a specific pathogen.)

When ceftiofur is used in major species, it may only be used in species and production classes for which FDA has approved its use, and it must be used in accordance with approved conditions of use. Under the ban, veterinarians would be permitted to use ceftiofur only in species and production classes for which the drug has been approved, and only in accordance with approved “conditions of use.” Conditions of use include the amount of drug that may be administered (“dose”), how often and for how long it may be administered (“frequency” and “duration,” respectively), and the means (“route”) by which the drug is administered (e.g., by intramuscular injection or in animal feed). These restrictions will prevent the continuous use of cephalosporins for prophylaxis, as the approved duration for ceftiofur is several days.

FDA will not ban extra-label use of cephapirin. The other cephalosporin drug approved for use in food animals, cephapirin, is not affected by the ban. This drug is older than many of the cephalosporin drugs used in human medicine, and FDA believes it is less likely to select for resistance to these newer drugs.

FDA will not ban extra-label use of any cephalosporin drug in minor species.  The ban only affects the use of cephalosporins in major species, such as cattle, swine, and poultry.  “Minor species” consumed by humans include sheep and ducks.  Because people eat these species less often than they eat major species, FDA believes they are of less concern.  This could be wishful thinking, however. Any misuse of antibiotics—in humans or other animals, whatever the species—selects for resistance and increases the prevalence of resistance genes (i.e., genes that confer resistance to antibiotics) in bacteria in the environment. Any increase in the prevalence of resistance genes increases the probability that bacteria with which humans have contact—through food and by other means, such as contact with water contaminated by bacteria—will be resistant. It would be better to end all practices that select for resistance genes, not just practices used to raise the species that people eat most often.

It is not clear yet whether farm groups, drug companies, and veterinarians will support the ban—or at least temper their opposition—but initial reactions were not all negative.  CLF will be drafting a comment to FDA in the coming weeks in support of the ban. We hope that you will do the same.  It does not have to be long or detailed—just a quick note urging FDA to implement the ban. If your background gives you special insight on this issue—say, you are a physician or a public health professional—you should note that as well.  FDA has largely failed to take meaningful action on the misuse of antibiotics in food animal production, but this is a step in the right direction.

FDA's proposed ban on cephalosporins, 2012