Vet's Opinion

Cephalosporins Aren’t Withdrawn From The Market

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It’s important to understand that the cephalosporins aren’t being withdrawn from the market. You’ll still be able to use ceftiofur products according to label directions when the drug is prescribed by a veterinarian for this use.

FDA’s Center forVeterinary Medicine (CVM) released a final rule in early January prohibiting some extralabel uses of cephalosporins in food animals. Let’s discuss which antibiotics are included in this group, the rationale, and changes coming down the road.

But, first of all, it’s important to understand that the cephalosporins aren’t being withdrawn from the market. You’ll still be able to use ceftiofur products according to label directions when the drug is prescribed by a veterinarian for this use.

Also under guidance of a veterinarian, and within the confines of extralabel use regulations, you will be able to use these products for off-label indications, but only if the rest of the label regimen is followed (dose, route of administration, duration, and frequency of treatment). Veterinarians will no longer have the ability to prescribe an altered regimen.

Additional prohibitions include the use of the cephalosporins for disease prevention in an off-label manner, and the use of a human labeled cephalosporin in food animals. By the way, the label for treating groups of cattle at high risk for bovine respiratory disease is a “control” label.

The veterinarian prescribing ceftiofur for your cattle will be able to discuss in detail any changes this CVM order will bring to your operation.

Cephalosporins, alongwithpenicillins, are subclasses of the beta-lactams, named because of the shared core chemical ring structure common to the group. The beta-lactams also share the common killing mechanism of attacking the bacterial cell wall.

Within the cephalosporins and penicillins are many chemical alterations that change the spectrum of bacteria against which the antibiotic is most effective. This CVM rule applies only to cephalosporins.

Much of the development of newer third- and fourth-generation cephalosporins has been driven by a quest to increase activity against gram-negative pathogens such as Salmonellaand E. coli. The third-generation cephalosporin approved for use in food animals is ceftiofur (Naxcel®, Excenel® and Excede® from Pfizer Animal Health). The commonly compared human third-generation cephalosporin is ceftriaxone. A fourth-generation human cephalosporin is cefipime.

Our challenge is that there are bacterial genetic mutations that have encoded for resistance to the beta-lactams. For example, the primary mechanism for resistance to cephalosporins is a genetic code which allows bacteria to produce enzymes that break down the antibiotic before it can kill the bacteria. Some of these resistance genes may be exchanged between bacteria.

The CVM’s final rule discusses members of two main families of resistance genes. Resistance to the third-generation cephlosporins is often because of enzymes encoded by the AmpC gene family. The fourth-generation cephalosporins were originally active against almost all the pathogens possessing AmpC. However, now a second gene family, the ESBLs, encodes for enzymes that inactivate the fourth-generation cephalosporins and there are data that suggest AmpC genes may also contribute to fourth-generation resistance.

These gene families are found in Salmonellaisolates from both human and food animal monitoring programs. The CVM final rule discusses major concerns about cephalosporin resistance in two animal classes, Salmonella entericaserovar Heidelberg from chickens, and serovars Newport and Typhimurium from dairy cattle. The final rule also cites 113 instances of violative ceftiofur residues in dairy cattle and 22 other instances, including beef cattle and veal calves, in the year ending June 25, 2009.

Reviewing these data, CVM concluded that “such extralabel use likely will cause an adverse event and therefore, presents a risk to the public health.” This is based on the agency’s concern that “certain extralabel uses of cephalosporins in food-producing major species are likely to lead to the emergence and dissemination of cephalosporin-resistant strains of foodborne bacterial pathogens.” FDA chose to take an action that spread across all food animal species and classes rather that specifying restrictions for certain animal groups. 

Mike Apley, DVM, PhD, is a professor in clinical sciences at Kansas State University in Manhattan.

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Three top U.S. veterinarians provide tightly focused discussion of specific beef cattle disease and welfare topics.

Contributors

Dave Sjeklocha

Dave Sjeklocha, DVM, is operations manager of animal health and welfare for Cattle Empire, LLC, Satanta, KS.

Mike Apley

Mike Apley, DVM, PhD, is a professor in clinical sciences at Kansas State University in Manhattan.

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