New federal rules will further restrict use of cephalosporin-class antimicrobials in most food animals starting April 5, 2012.
The Food and Drug Administration published Jan. 6 in the Federal Register an order that will limit extralabel use of cephalosporin antimicrobials in cattle, chickens, swine, and turkeys by banning disease prevention uses and limiting prescription applications to those that follow the dose, frequency, duration, and route of administration specified for each species on the drug labels. The action is intended to reduce the risk of humans contracting infections with cephalosporin-resistant bacteria.
"Resistance to certain cephalosporins is of particular public health concern in light of the evidence of cross-resistance among drugs in the cephalosporin class," the Federal Register notice states.
"Importantly, resistance to ceftiofur compromises the efficacy of ceftriaxone, a first-line therapy for treating salmonellosis in humans."
The order contains exceptions for extralabel uses of cephapirin products, which have a narrower activity spectrum and no uses in human medicine, as well as for extralabel use for treatment or control of diseases not listed on the label when the use adheres to labeled dosage regimens for the species and production class. Extralabel use will also be allowed in other food-producing "minor species" such as ducks, goats, and rabbits.
"FDA may further restrict extralabel use of cephalosporin antimicrobial drugs in animals in the future if it has evidence that demonstrates that such use has caused or likely will cause an adverse event," the notice states.
The Food and Drug Administration indicated resistance to ceftiofur,
which is used in veterinary medicine, coincides with resistance to
human-use ceftriaxone. These charts of resistance among Escherichia
coli isolates are based on data published in the 2009 edition of the
National Antimicrobial Resistance Monitoring System Retail Meat Annual
Report, which is produced by the FDA.
(Click image to view larger version.)
Background information included in the January order states that the agency is particularly concerned about the extralabel use of cephalosporin drugs not approved for use in the major food-producing species because "very little is known about the microbiological or toxicological effects."
Effects on antimicrobial resistance
Cephalosporin antimicrobials are used in human medicine to treat conditions such as pneumonia, Staphylococcus aureus skin and soft tissue infections, upper respiratory tract infections, and diabetic foot infections, the notice states.
It indicates the most substantial public health risk associated with antimicrobial resistance is infection resulting from contact with food that contains resistant pathogens because of antimicrobials administered to the source animals.
The agency cites National Antimicrobial Resistance Monitoring System data that indicate, by 2009, about 14.5 percent of Salmonella isolates from cattle were resistant to ceftiofur, 12.7 percent from chickens were resistant, 12.4 percent from turkeys were resistant, and 4.2 percent from swine were resistant. Those figures are up from 1997 when none of the cattle or swine isolates were resistant, 0.5 percent of the chicken isolates were resistant, and 3.7 percent of the turkey isolates were resistant.
Resistance to ceftiofur, which is used in veterinary medicine, coincides with resistance to ceftriaxone, which is used in human medicine, the notice states. Ceftiofur use in dairy herds is also connected with an increased prevalence of resistant Escherichia coli.
(Click image to view larger version.)
Previous order would have banned more uses
FDA published in July 2008 an order that would have prohibited any extralabel cephalosporin use in food animals. That order would have taken effect within 90 days, but the FDA had extended the comment period and later revoked the order, citing the need to fully consider comments.
FDA officials had indicated revised restrictions on extralabel cephalosporin use would be published, at one time indicating the new order was expected in summer 2009.
The AVMA opposed the 2008 order, told the agency that the restrictions were more likely to harm food safety than improve human health, and requested that the FDA delay the order and further assess the risks and benefits.
As with the January 2012 order, the FDA Federal Register notice for the 2008 order cited concerns that reduced susceptibility to veterinary-use ceftiofur was connected with decreased susceptibility to human-use ceftriaxone. The agency further noted in the 2012 order that cephalosporin antimicrobials are critical for treatment of infections in humans, and expanded spectrum cephalosporins such as ceftriaxone and cefotaxime are the drugs of choice for invasive Salmonella infections in children.