For only the second time, federal regulators have restricted the use of a class of antibiotics in animals because of the potential development of antibiotic-resistant pathogens.
The U.S. Food and Drug Administration (FDA) this week issued a rule
banning some common extralabel uses of cephalosporins in livestock that it deemed present a significant risk to public health. Cephlosporins are widely used in human medicine, for instance to treat pneumonia and a number of common infections in children.
The rule applies only to certain extralabel uses in four species of food animals: pigs, cattle, chickens and turkeys. It has no effect on veterinarians' ability to prescribe cephalosporins for extralabel uses in other species, including companion animals.
"Extralabel" refers to using a drug in a way that has not been approved explicitly by the FDA. For example, a veterinarian might prescribe an antibiotic that is approved for the treatment of pneumonia in cattle to treat a cow for a different disease, or prescribe the antibiotic at a dose different from the FDA-approved dose. Prescribing extralabel uses of drugs is common and accepted in medicine.
Under the new rule, veterinarians can continue to prescribe cephalosporins to livestock to treat non-indicated diseases provided the drug is approved for the species being treated and the approved dose regimen is followed. In addition, cephapirin products are not covered by the new rule, because the FDA believes that this earlier generation of cephalosporin drugs is not likely to generate potentially dangerous antibiotic resistance.
The FDA presents the justification for the new restrictions in a posting
in the Federal Register. The agency points to two specific areas in which extralabel cephalosporin use is a particular concern: high doses of ceftiofur administered to culled dairy cattle shortly before slaughter, leading to violations of antibiotic residue standards in the animals' carcasses; and the routine injection of ceftiofur into chicken and turkey eggs at commercial hatcheries. Both of these uses, the agency states, stand to significantly increase human exposure to ceftiofur-resistant bacteria.
Federal monitoring data show that resistance to ceftiofur in Salmonella
samples from chickens, turkey, cattle and humans has increased sharply since the late 1990s. While ceftiofur is not used in human medicine in the United States, bacteria resistant to it frequently are resistant to other important cephalosporins used to treat human illnesses.
The FDA issued its first restrictions on cephalosporin use in 2008 in a rule that would have banned extralabel use in food animals without exceptions. But after groups representing veterinary medicine and the meat and pharmaceutical industries protested that the prohibition was too broad, the agency withdrew the rule for reconsideration.
In 2005, the agency cited drug-resistance concerns to force the withdrawal of enrofloxacin (brand name Baytril), which was pulled following a five-year legal battle with its sponsor, Bayer Corp. Baytril was used for the treatment of respiratory diseases in poultry.
Dr. Christine Hoang, assistant director of scientific affairs for the American Veterinary Medical Association, said her organization was pleased that the rule on cephalosporins announced Wednesday is more targeted than the 2008 proposal, and that it will allow livestock veterinarians to retain some flexibility to treat patients. She said it is not clear what impact the restrictions will have on animal health.
Dr. Fred Gingrich, a mixed-animal practitioner in Ashland, Ohio, with a focus on dairy cattle, said the regulation would have a "very minimal impact on our ability to treat sick animals," because veterinarians will still be allowed to use ceftiofur for non-indicated diseases in cattle so long as the approved dosages are followed.
Gingrich said at least some of the high levels of ceftiofur residues in dairy cattle cited by the FDA are likely due to mistakes by producers who administer the drugs. For instance, older formulations of the drug require that use be stopped just four days before slaughter, while newer, longer-acting formulations must be withheld 13 days before slaughter; confusion between the two can lead to violations, Gingrich said.
Dr. Tim Cummings, a poultry specialist at the University of Mississippi College of Veterinary Medicine, estimated that the restriction on the injection of ceftiofur into hatchery eggs would reduce survival of chicks through their first week by an average of 0.25 percent. He noted that another antibiotic, gentamicin, which will not be affected by the new FDA rule, is commonly used in the same way.
Cummings and Dr. Lynne Luna, a poultry specialist in Eugene, Ore., and a consultant with the Veterinary Information Network, a professional online community, both said that while the prohibition on ceftiofur will not be devastating, it will noticeably narrow a poultry veterinarian's treatment options.
"It's like a lot of things," Cummings said. "We can live without it, but it's just another tool in our chest that we would prefer to have available if we need it."
Luna noted that the restriction on extralabel use in production chickens could complicate the treatment of birds from backyard flocks, as well.
The FDA is accepting comments on the rule through March 6 and will review the input before the regulation goes into effect, scheduled for April 5.
The new rule has no impact on the issue that dominates the debate over food animals and antibiotic resistance: the millions of poun
ds of antibiotics, including penicillins and tetracyclines, administered annually in the United States without veterinary oversight to promote growth and prevent disease in livestock that are not clinically sick.
The FDA issued a draft policy document
in June 2010 indicating that it supports restrictions on the use of antibiotics to promote growth and that it believes veterinarians should play a stronger supervisory role over the delivery of antibiotics to livestock through feed. An agency spokeswoman said the FDA intends to issue the final version of the policy "in the near future."
In May 2011, the VIN News Service published a four-part series
on the debate over antibiotics in livestock.