• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Animal & Veterinary

  • Print
  • Share
  • E-mail

The Infectious Diseases Society of America by Ruth Lynfield, M.D., University of Minnesota

 DR. LYNFIELD: I too want to thank the organizers for asking for an IDSA perspective. IDSA is the Infectious Diseases Society of America. So what I am going to try to do is provide the human medicine perspective on the issues.

(Slide)

Just to explain the cover slide here. One thing that IDSA is really working on now is to highlight the problem of the lack of antibiotics and so that is why the “Bad Bugs Need Drugs. Ten new antibiotics by 2020.”

(Slide)

IDSA consists of physicians who work in patient care that make up a little bit more than half of our membership. We also have those who are involved in research, education, public health, and we do welcome veterinarians as well. We have now about 9,000 members.

(Slide)

One of the fathers in the field of infectious diseases is Alexander Fleming. What you may not know is he also is the father of antimicrobial stewardship. A New York Times article from 1945 quoted Sir Alexander Fleming as saying,

“The thoughtless person playing with penicillin is morally responsible for the death of the man succumbing to a penicillin-resistant infection.”

(Slide)

As all of you know, antibiotics are associated with antibiotic resistance and a lot of the work done in NARMS has been very useful in trying to look at foodborne pathogens. And as has been discussed multiple times, antimicrobial use in food animals consists of a variety of methods, growth promotion with low doses and long duration, disease prevention whereby high doses of a short duration may be given during a high-risk period, and treatment of infectious diseases.

(Slide)

From the human medicine angle, there is great concern about antimicrobial use in food animals because these agents are often the same or in the same classes as those that are used in human medicine.

And very large quantities of these agents are used in food animal production. And this provides favorable conditions for the selection, persistence, and spread of antimicrobial resistant animal and human pathogens.

And as we have discussed in this conference, food animals and food are traded worldwide so what happens globally is of concern globally to all of us.

(Slide)

Here is a chart that you probably have seen in the past. There is some debate about how much antimicrobial use is used in animals and I am so delighted to hear that we will be getting data and that folks in the poultry industry are committed to getting us accurate data because we really need to know use on the animal side and use on the human side in order to approach the issue.

However, it is thought that the United States far and away exceeds other countries in the use of antibiotics per kilo of meat produced.

(Slide)

As has been discussed, antimicrobial use in food animals can select for resistance, bacteria can be transmitted to humans through food, either through consumption, through exposure during handling of food, or through the slaughter process. Bacteria can be transmitted via handling of animals in their environment such as manure. There can be contamination of ground and surface water by resistant bacteria, and undigested antibiotics from manure.

(Slide)

We have talked a bit about the circle of antibiotics and how really the impact in people of antimicrobial use is from many different means. Through certainly the use of antibiotics in people themselves, but also there is an impact from agriculture and there is an impact from the environment as well.

(Slide)

We have talked a lot about Campylobacter. We do know that when fluoroquinolones were approved for use in 1995, resistance in human isolates rose. This temporal relationship has also been observed in other countries, the United Kingdom, Spain, and the Netherlands.

We do know fluoroquinolones resistant Campylobacter has been found in retail chicken products and that molecular subtyping of retail chicken product isolates and human isolates have been indistinguishable.

(Slide)

Here is just a graph of data from Spain. Fluoroquinolones were licensed in 1990 and here you can see that resistance in Campylobacter isolates from humans rose dramatically after that. 

(Slide)

We did talk about other foodborne pathogens, multidrug resistant clones of Salmonella and Salmonella Typhimurium DT-104 in particular.

(Slide)

Here are some NARMS data looking at multidrug resistance in Salmonella, Shigella, and E. coli O157. 

(Slide)

We talked a bit about virginiamycin most recently, I think, when industry came up to talk. There is concern about Enterococcus faecium and the transfer of genes. We do know that commensals like Enterococcus and E. coli may be reservoirs for resistance in humans. There are now data emerging on E. coli, especially that associated with poultry and the similarity between those isolates that are uropathic in people.

(Slide)

The epidemiology is complex. It involves the transfer of resistant zoonotic bacteria from food animals to humans, transfer of resistant commensal bacteria from food animals to humans, and transfer of resistant genes horizontally to pathogenic bacteria.

(Slide)

We have seen an increase in the community of resistant E. coli. It is thought that drug resistant isolates may be acquired by people through food and food animals in addition to the selective pressure in the community of antibiotics used in humans.

(Slide)

We know that there are resistant elements, that there are -- we have talked about plasmids, about integrons, other genes that can transfer horizontally and spread resistance.

(Slide)

One thing that I think all of us in this room are concerned about is really doing our best to carefully define the epidemiology. We have heard that raised a lot. 

I really think that is tremendously important because if we don’t understand the bits and pieces, we cannot effectively control this giant public health threat. And it really is a huge public health threat of antibiotic resistance.

(Slide)

Yesterday we did have a lot of presentations from Europe and from WHO. We very strongly feel that these are critically important principles, that there should be obligatory prescriptions for all antimicrobials used in food animals; that there should be the termination or rapid phasing out of antimicrobials for growth promotion if those same antibiotics are used for the treatment of humans; that there should be a strong national system to monitor antimicrobial use in food animals and in people.

(Slide)

That pre-licensing safety evaluation of antimicrobials should be done with the consideration of potential resistance to human drugs. There should be monitoring of resistance and guidelines for veterinarians.

I do know that there are very judicious antibiotic use for swine veterinarians, for poultry veterinarians, for beef cattle veterinarians. The same important principle of antimicrobial stewardship needs to be taken very seriously. 

The horse has left the barn, but hopefully we can still do something about antibiotic resistance.

(Slide)

One approach is to really look carefully at the antibiotics that are being used. Not all antibiotics are equal in terms of their impact on human medicine. The World Health Organization has ranked antimicrobials and we need to be very mindful when we think about human medicine of the impact of the use in agriculture and the impact in human medicine.

So, in fact, fluoroquinolones, macrolides, and third- and fourth-generation cephalosporins, in fact, are considered critically important by the WHO for use in human medicine.

(Slide)

There are some data that when antibiotics are removed that resistance decreases. Now the whole area of resistance and antibiotic use is very complex. It is going to vary depending on the antibiotic. It is going to vary depending on the resistance mechanism and how much time it may take for wild-type strains to repopulate.

It will also depend on the lifespan of the animal. But here you can see very nicely Avoparcin being banned and Vancomycin resistance in E. faecium in broilers dropped dramatically.

(Slide)

There also has been a lot of discussion about the Danish data. I am not sure why it is so controversial but, in fact, this is an article that has just been published that goes through the Danish experience in which they do indicate that antimicrobial consumption per kilo of pig produced in Denmark decreased by more than 50 percent. That was associated with maintaining productivity. In fact, perhaps even increasing productivity, suggesting that long term swine productivity was not negatively impacted by a ban on antibiotic growth promoter use.

(Slide)

You have seen the data from Canada presented how there was voluntary withdrawal of ceftiofur and there was an associated drop in third-generation cephalosporin-resistant E. coli and Salmonella in chickens and in resistant Salmonella in people.

(Slide)

So combating antibiotic resistance, what can we do? Stewardship is critically important, both for human medicine as well as agriculture.

Infection prevention and control; there is great emphasis now on this in human medicine. I think that is an area that needs to be explored more on the veterinary side and the agriculture side.

Immunization, in human medicine the use of pneumococcal conjugate vaccine in young children dropped the proportion of resistant pneumococci. So immunizations can have an effect. They can also have an effect on improving animal health and not relying on antibiotics.

Data are critically important on antimicrobial use as well as surveillance for antibiotic resistant bacteria. Novel antibiotics are always on our list. Unfortunately, in human medicine, as you have heard, the pipeline has been dry. We have very few new antibiotics and it has been discussed. This is primarily because it is not very lucrative for pharmaceutical companies to invest in a drug which has a defined lifespan that people take for a short period of time as opposed to a drug like an anti-hypertensive that people would take every day for the rest of their lives.

(Slide)

The IDSA has worked on trying to get legislation moved on the strategy to address antimicrobial resistance, also known as the STAAR Act.

This encompasses a number of approaches, leadership and coordination of the existing Federal Interagency Taskforce on Antimicrobial Resistance with the idea of, in fact, having on the HHS level an Antimicrobial Resistance Office.

To have external expert input through an advisory board, surveillance and research network, interagency strategic research plans, strengthen prevention and control, and collection of human and animal antibiotic use data.

(Slide)

This is an article that came out in 2008 where IDSA discussed a call for action to the medical community about the epidemic of antibiotic resistant infections and in it some of the recommendations included reassessment and strengthening of FDA’s regulatory authority relating to the use of antibiotics in food-producing animals.

And to more appropriately regulate the use of antibiotics in agriculture, including the phasing out of the use of antibiotics for growth promotion.

(Slide)

In March of this year, IDSA provided testimony concerning fiscal year 2011 funding at the FDA in which IDSA felt it was very important to provide funds to allow FDA to complete, update and publish reviews on the safety of antimicrobials of importance to human medicine that currently are approved for nontherapeutic purposes in food-producing animals, as well as additional funding for NARMS.

(Slide)

So our recommendations are as follows: We do think it is important to discontinue antibiotics for growth promotion and feed efficiency. We are really left now with some infections, some Gram-negative infections which have no antibiotic that can be used. We are very concerned that we are going to move into a pre-antibiotic era.

There are some data that exchange of genetic elements and exchange of resistance genes -- this has to be a concern for everyone. All of us, on the human side and on the animal side and on the plant side, all of us need to be concerned about appropriate antibiotic use.

We think it is important that there be veterinary oversight and that for treatment there should be directed therapy for a specific pathogen. It sounds like this is frequently done and we want to promote that. Carefully review the indications for prophylaxis and prevention.

To evaluate pre-licensure whether a drug important for human medicine, as well as drugs that are already licensed, post-licensure monitoring for drugs that are critically important to human medicine. To monitor the antibiotic use, to conduct surveillance, among animals, retail meats, as well as infections in people and in animals.

(Slide)

With that, I would like to thank you for all of your efforts in trying to curb the public health threat of antimicrobial resistance.

(Applause)

DR. FRYE: Thank you Ruth. Then we will finish with Steve Roach with Food Animal Concerns Trust.