Animal & Veterinary
Antibiotic Breakpoints: Methods for Determining and Use by Veterinary Medical Community
Dr. Tom Shryock
DR. SHRYOCK: Thank you very much for that kind introduction, Andy. I appreciate being up here with fellow alumni. It is my great pleasure on behalf of the NCCLS to address you today on the Veterinary Antimicrobial Susceptibility Testing Subcommittee.
And since time is limited, I am going to run through this fairly quickly as far as organization. If you want to check out the website, NCCLS.org, there is much more information about the organization. It is a standards and guidelines writing organization. Microbiology is just one of several components in clinical laboratories that this organization encompasses.
The NCCLS process itself revolves around a tripartite process of participation from the professions, government and industry. And it uses a consensus process to derive the documents that it produces.
With respect to the development of the AST, or antimicrobial susceptibility test methods, I would like to point out that the current methods are adequate for testing rapid growing organisms. And the list includes Enterobacteriaceae, Staph., Strep., some miscellaneous pathogens.
What is obvious by its omission and germane for this particular meeting is Campylobacter. There are documents that are available for human pathogens as well as for veterinary pathogens. In all of these documents, there are really two components as Al had outlined. There is a lot to do with quality control and methods including standardized procedures, QC. And these deal specifically with the MIC test and the auger dish diffusion test.
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And you can see here in this example of a single dose, there is clinical cures ---
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And the red line here would be the intended breakpoint for susceptible organisms. So what we would like to do is look at time after dosing to see if, in fact, we can achieve a concentration greater than that MIC. You can see in this example here an eight microgram per ml can be achieved for susceptible.
Now, when we come to the scatter gram data set, MIC is listed on the left. Zone and inhibition diameters on the top side here. At this eight or less microgram per ml level, which was indication of a clinical success, you can see there is a large cluster.
So that would be where we would draw the line and say, okay, everything eight or less is susceptible. We go up one dilution for intermediate buffer zone. And then anything above that at 32 or greater would be termed resistant.
You will note also that in this susceptible population, there is a range of MICs from eight, four, two and one and so on. There is really no way to distinguish between differences in clinical outcome of those isolates with lower MICs versus those that maybe are a little higher. They are all susceptible in the eyes of the NCCLS as far as clinical outcome.
So in this particular example, this is what you would see in the document as far as how those breakpoints would be reported.
Obviously, the establishment of the interpretive criteria are not without difficulties and there is lots of debates usually revolving around the correlation of these data points. The decreased susceptibility aspects here really have not been established for any agent at this point in time.
There is lots of demographic discussions, controlled clinical trials versus community and animal disease models. Those all get factored in at some point or another. As Al mentioned, there are some ethical issues of treating patients, be they animal or human, with high MICs since you would expect clinical failure to result.
With regard to Campylobacter testing on the methodology issues, Bob Walker at Michigan State is heading up a working group that has members from both the AST and VAST. And the objective here is to standardize the methodology, to define appropriate quality control strains, identify test media, etcetera.
The interpretive criteria ultimately to be set for treatment of Campylobacteriosis would have to fall into that AST realm since there are no veterinary antimicrobials that have a claim against Campylobacter. This would entail a specific sponsor presentation as it would for any other antibiotic or disease-causing agent to establish those interpretative criteria. Once the methods are available, they can be applied to epidemiologic purposes.
So just to sum up here and get us out to the break, let me say that the interpretive criteria then are basically set on three different parameters: the efficacy, pharmacology and scattered gram or epidemiology data. There is as yet in the eyes of the NCCLS no approved methodology available for Campylobacter testing. It is being developed at this point.
And finally, the interpretive criteria which was validated for Campylobacter will need to be set by the NCCLS AST group, as well as the FDA upon appropriate presentations of data and determinations. So that concludes the remarks that I wish to make this morning. And I will open it up for questions.
DR. BEAULIEU: Any questions for Dr. Shryock?
(Away from microphone.)
MR. : Doctor, how do you know where the issue is species-specific MIC ---?
DR. SHRYOCK: The question was how do we deal with species-specific issues given the fact that there is different parameters of absorption and metabolism, etcetera. Each sponsor brings forward that specific kind of data for the pharmacology in the target animal species for which interpretive criteria are being requested. And that is what makes this a real challenge and really sets the basis for the need to do this on an animal-specific basis.
For example, when we have a particular antibiotic that is used in two different food animal species, say beef and poultry, the sponsor needs to bring forward the relevant information for each one of those species. And the break points could be different between those different species because of the pharmacologic behavior of those -- of that agent in the two different species. They are different.
DR. BEAULIEU: Any other questions? We are running a little behind this morning. We got a late start. I would beg your indulgence in getting back here within 15 minutes. If that doesn't suffice, I would remind you that a long break equals a short lunch. I will see you in 15 minutes, folks.
(Whereupon, a brief recess was taken.)
DR. BEAULIEU: Take your seats, folks, so we can get started. Hopefully folks will join us almost immediately. Our next speaker is Dr. Kirk Smith. Dr. Smith has a D.V.M. from Iowa State, Ph.D. from the University of Georgia. He is currently Supervisor of the Food-borne, Vector Borne and Zoonotic Diseases Unit of the Minnesota Department of Health.
He was formerly with the Epidemic Intelligence Service at CDC. Dr. Smith is going to speak to us today about epidemiology of Campylobacter in humans.