Anyone believing the antibiotic-resistance issue would just “go away” would have been sorely disappointed over the past month or two. If anything, the issue has moved further up the list of public priorities as media and government shower the topic with attention.

One thing that has not happened: As of the mid-April deadline for this publication, the FDA had not delivered its final veterinary feed directive (VFD) rule, which it had indicated will publish this spring.

But as the industry awaits that final rule, other events have brought antibiotic resistance to the forefront, increasing the urgency for the livestock industry to expand and publicize its focus on judicious antimicrobial use.

First, in late March, the White House released its National Action Plan for Combating Antibiotic-Resistant Bacteria, a five-year, $1.2 billion plan to fight antibiotic resistance that includes human and animal health factors.

The next related item to make the news was an FDA report on 2013 antimicrobial sales for use in food animals, released on April 10. The report, which shows small year-over-year increases in the volume of antimicrobials sold, provided further ammunition for groups fighting for further restrictions on use of these products in animal agriculture. This comes in spite of FDA statements within the report that the sales data do not provide a reliable indicator of actual use.

Also in mid-April, FDA released its latest retail meat data from the National Antimicrobial Resistance Monitoring System (NARMS), showing some modest reductions in the levels of resistant pathogens found in retail meats during 2012 and early 2013 (see sidebar).

Behind this activity, the FDA has been working to implement its strategy for encouraging judicious use of antimicrobials, which centers around two initiatives. The first of these, FDA Guidance to Industry 213, will lead to removal of production or performance label claims from medically important antibiotics, limiting their use to prevention, control or treatment of disease.  The second is the proposed VFD rule, which, once implemented, will place virtually all feed-grade antibiotics under the VFD, essentially ending over-the-counter sales of those products once the rule is fully implemented by late 2016.

VFD defined

According to FDA documents, a drug approved as a VFD drug is limited to use only under the professional supervision of a licensed veterinarian, within the confines of a valid veterinarian-client-patient relationship. The veterinarian examines and diagnoses animal conditions and determines whether a condition warrants use of a VFD drug. If it does, the veterinarian will issue signed VFD order containing information specified by regulation. Extra-label use of a VFD drug (or any drug) in or on an animal feed is strictly prohibited. The veterinarian keeps a copy of the VFD order and provides the completed and signed original and a copy to the client. The client keeps the copy and gives the original VFD to the feed manufacturer issuing the VFD feed. The VFD order allows the VFD feed to be issued to the client for feeding to the animals.

Measuring the impact of changing antibiotic rules

Ever since the FDA issued its Draft Guidance 213 and the proposed VFD rules in 2013, veterinarians and industry stakeholders have wondered about measurement.

The FDA rules, of course, are intended to encourage judicious use of antimicrobials and thus reduce the risk of development of antimicrobial resistance in pathogens, and the industry generally has supported this effort. But, many have asked, how will we know whether the rules, once implemented, have any positive impact? Will the industry be able to measure and report significant reductions in antibiotic use or lower prevalence of resistant pathogens?

During the recent National Institute for Animal Agriculture (NIAA) conference in Indianapolis, the NIAA Antibiotics Council discussed program goals and metrics with officials from the FDA and USDA.

Craig Lewis, DVM, MPH, DACVPM, from FDA’s Center for Veterinary Medicine (CVM), says the agency sees a need for collecting more on-farm data on antibiotic use and resistance trends, and is currently developing a plan for collecting, analyzing and applying that data.

Currently, FDA cooperates with the USDA and the Centers for Disease Control and Prevention in NARMS, and also collects data on total sales of antimicrobials for use in animals. More data will be needed to augment those efforts and determine the effectiveness of FDA’s strategy for judicious use of antimicrobials.

In 2014, Lewis says, CVM substantially enhanced its annual survey on the quantity of antimicrobials sold for use in animal agriculture. Addition of on-farm use and resistance data, coupled with data currently collected through NARMS, will provide information for assessment of the impacts of the judicious use strategy.

When the FDA initiated its strategy in December 2013, it set a three-year timeline for implementation, including a plan to finalize the proposed VFD rule early this year. Also early this year, Lewis says CVM plans to hold a public meeting to discuss the on-farm data-collection strategy to support the judicious-use strategy. By later this year, CVM hopes to have the data-collection plan in place and begin collecting baseline data, prior to full implementation of Guidance 213 and the VFD rule in December 2016. By late 2016 and into 2017, with the changes in antimicrobial use fully implemented, CVM plans to implement its data collection and comprehensive assessment of antimicrobial use and resistance trends. Lewis says CVM intends to publish its first assessment report showing changes in antimicrobial use in 2018.

USDA also will play a role in assessing progress in fighting antimicrobial resistance, and Larry Granger, DVM, senior leader for veterinary services at the USDA’s Animal and Plant Health Inspection Service, outlined his agency’s perspectives during the conference.

Granger also noted that antimicrobial resistance is a high priority for the Obama administration, referring to the recent report and National Action Plan on Combating Antibiotic Resistance based on the recommendations of the president’s Council of Advisors on Science and Technology.

Among stakeholders outside of agriculture, Granger says, many believe the health risks associated with antimicrobial resistance are best resolved by reducing use. However, he says, data on antimicrobial sales alone are a poor indicator of actual use across production types and livestock species.

Also, Granger points out, the VFD rule is not designed to limit appropriate use of antimicrobials. Instead, by increasing veterinary oversight, the rule should help ensure the right drugs are targeted toward appropriate pathogens at the correct dosages, with treatment records and results recorded.

Granger says USDA, like FDA, advocates collection and dissemination of more science-based, actionable, quantitative antimicrobial-use data coupled with information on resistance trends. His agency’s National Animal Health Monitoring System could be enhanced to conduct more epidemiological work to correlate use patterns with resistance. And he adds, the cooperative NARMS program could be enhanced to conduct biological sampling on farms or slaughter plants, with tests for antimicrobial sensitivity then related back to farm practices.


Current NARMS reporting shows improvement

In mid April, the FDA released its 2012 Retail Meat Report, which summarizes key findings in antimicrobial resistance related to raw chicken, ground turkey, ground beef and pork chops collected at retail stores. Concurrently, the agency released its 2013 Retail Meat Interim Report, which contains data from January-December 2013 and focuses specifically on Salmonella.

The reports document several encouraging trends. Although current cephalosporin resistance levels are above 2002 levels, a recent decrease in third-generation cephalosporin resistance among poultry meats continued in 2012 and 2013. Resistance in Salmonella from retail chicken declined from a peak of 38 percent in 2009 to 28 percent in 2012 and continued to decline to 20 percent in 2013. Resistance in ground turkey peaked in 2011 at 22 percent and declined to 18 percent in 2012, falling to 9 percent by 2013.

Salmonella from retail meats remained susceptible to ciprofloxacin, one of the most important antibiotics for treating Salmonella infections. Similarly, Salmonella from retail meats were susceptible to azithromycin.

While multi-drug-resistant Salmonella (resistant to three or more classes of antibiotics) was detected in all retail meat sources, there was a continuous decline in the overall proportion of Salmonella isolates that were multi-drug resistant between 2011 and 2013.

In 2012, only 1 percent of Campylobacter jejuni from retail chicken was resistant to erythromycin, the drug of choice for treating Campylobacter infections.

In one finding of concern, FDA has not observed any consistent changes in fluoroquinolone resistance among C. jejuni and E. coli recovered from retail chicken, even though the agency withdrew approval for the use of fluoroquinolones in poultry in 2005.

For this article and more on meeting consumer expectations, calcium balance in dairy cows, feeding waste milk to calves and utilizing ultrasound in beef herds, see the digital edition of the May-June issue of Bovine Veterinarian