July 13, 2015

(Dan) Hey folks, welcome to DocTalk. Dr. Dan Thomson here from Kansas State University and my guest today is going to be Dr. Mike Apley and we’re gonna go and talk about Antibiotics 101. Have you had questions about how antibiotics work and how we make different choices and the history of antibiotics, well you stay tuned, enjoy the show and listen to what Dr. Apley has to say.Closed Captioning brought to you by AgriLabs, the Perfect Pairing of Performance and Value.

(Dan) Hey folks, welcome to DocTalk, Dr. Dan Thomson here at Kansas State University with my good friend and colleague Dr. Mike Apley, who is a professor here at the College of Veterinary Medicine at Kansas State University and he is a boarded clinical pharmacologist who works a lot internationally nationally, locally on antibiotic issues surrounding food animals. And we have had shows where we’ve talked about antibiotics, about judicious use which… and working with your veterinarian, but one of the things we need to… every once and awhile back up to is what are these things? And so, what are antibiotics and kind of give us some of the history of these things, Mike. (Mike) Well antibiotics have always been here for a lot of us, we’ve just always known them and had the option to use them. Actually our first real antibiotics discovery was…well we used the arsenicals back at the turn of the century, starting around the early 1900’s. But they had a lot of side effects. In 1928, Sir Alexander Fleming, went on a vacation and he put some petri dishes with staph aureus growing in them and disinfectant so they’d be killed off while he was gone. But some of them didn’t get under the disinfectant he was actually discovering the activity of the arsenicals on the staph. Well he came back from vacation and low and behold some of them had been submerged and there were spots where the staph hadn’t grown, it had been killed off. And it was from spores blowing in the window and landing there and that mold produced the penicillin. He isolated the penicillin and it was almost a curiosity for a while, they published a lot on it. And it was in the late ’30s that Florey and Chain down in Australia figured out how to mass produce in large quantities. And then the first use of penicillin, outside the military, remember this was right before World War II, when it went to mass production and the U.S. geared up to produce it primarily for military use. It was 1942, the Tropicana Night Club fire in Boston, Massachusetts, a lot of burn victims and staph is a real problem, so they used it on them. And was taken to the hospital actually the penicillin was in a military convoy because it was classified as really military secrets. So it was 1942, the first wide spread use. We had sulfas before then, they were discovered really in 1935 and that brings up the difference between an antibiotic and and antimicrobial. Penicillin is an antibiotic because it is produced by one organism and inhibits the growth of another. Sulfas are a totally synthetic, the first one was a dye that they tested in rabbits and found the antimicrobial activity in there. So it’s completely synthetic. And so it’s an antimicrobial which includes the antibiotics. We have listeners out there who were alive when their only option was a sulfa and maybe a few that there wasn’t even really a sulfa available when they were very young and had an infection. So our antibiotic era is really a life span long, that we’ve really truly had effective antibiotics too. (Dan) Yea, it’s hard to imagine when you look at all the different classes and compounds that we’ve developed since then, but now that bottle has come to a neck and narrowed where we’re not producing or discovering a lot more antibiotics classes or compounds. (Mike) The last two novel classes, completely new chemistry, were 2000 and 2003 and that was for human. Before that it was like 1978 when the fluoroquinolones were first released. So, ’50s, ’60s through the ’70s it was like we had beaten infectious disease we’ve conquered it. We’re now realizing that’s not true. And we’re going to have to look at some completely novel mechanisms of action against bacteria to advance more options. (Dan) Cool. We’re gonna take a break folks, when we come back, more on antibiotics with Dr. Mike Apley.

(Dan) Hey folks, welcome back to DocTalk, Dr. Dan Thomson and Dr. Mike Apley from Kansas State University, College of Veterinary Medicine where Dr. Apley is a professor and a clinical pharmacologist here at the veterinary school. He teaches students about antibiotics, about other drugs, other compounds, and he works a lot within agriculture and does a lot of service for agriculture whether it’s on a national or international level. And when we talk about antibiotics and keeping the technology available for us on the farm and ranch. And let’s get into some of these about how these antibiotics work. Because it’s amazing to me, we put it in the animal and they go find the bacteria or the bacteria find it, or they run into each other, or whatever, but what are some of the things that we do that differentiate antibiotics. (Mike) Well the antibiotics are different by their chemical structure, so when we talk about the macrolides, or the penicillins, or the cephalosporins, it’s a group that’s very chemically similar and then they differ by different groups hung on there that give different activities. So, for example, the fluoroquinolones, it recognize a danofloxacin or enrofloxacin. (Dan) Baytril or …. (Mike) Yea and those the very first ones really didn’t have that good of pharmacokinetics, as far as how they moved in the body. They had some side effects and then they kept working with them and adding a group here or subtracting one here to get to the ones that we have today, which are really quite effective and that’s true for all the groups. So, the groups when we talk about them as groups or chemically similar and they have different ways of acting. A lot of them work by binding to the part of the bacterial cell that produces proteins and knocking out its ability to produce proteins. Others work by working directly on the DNA and bacteria have DNA just like we do. And again the example before quinolones, they work by sabotaging the splitting and replication of the DNA. The sulfas, one of the first ones, they work by actually inhibiting the bacterias ability to produce folic acid. (Dan) So when you get into this, one of the things that we always talk about are static or cidal. These are either bacteria static or bacteria cidal. What’s the difference between static and cidal antibiotics? (Mike) There’s two ways we do it in the lab, one is by how far apart the concentration is it takes to just inhibit growth. So, if you take the antibiotic away, it will regrow, how far that concentration is for how much it takes to completely sterilize the culture. The other one is how fast it kills. So it’s not a black or white, it’s being separated by so many magnitudes. (Dan) But in general the difference between a static drug and a cidal drug would be…? (Mike) One slows growth, and the immune system comes in and cleans them up. The other one tends to kill the bacteria. Cidal tends to kill more and then the immune system still has to come in and clean up the mess, but both statics and cidals can work. And there are a lot of things that make up how an antibiotic works. Static versus cidal is one of many, so it’s something to be aware of, but it’s not the end all on one drug being better or worse that the other. (Dan) Right, right, it’s just a difference in the mechanism. When we come back I want to talk some about the long acting and some of the differences between in oral and injectables and just how these antibiotics differ. Thanks for being here. Thanks for watching DocTalk, more after these messages.

(Dan) Hey folks, welcome back to DocTalk. Dr. Dan Thomson here with Dr. Mike Apley. Dr. Apley is a clinical pharmacologist here at the Kansas State University College of Veterinary Medicine and serves all the agricultural food animal industries in protecting this technology we call antibiotics. And working with these industries to help support judicious use of antimicrobials. And we talked about static versus cidal. Slowing growth, versus killing, which both of them are effective but what about the long acting antibiotics? What does that mean? (Mike) Frankly I’ve gone to the single injection term, because it helps me understand better. But long acting means after one injection you have a longer duration during which you can measure drug concentrations in the body. And in the last 10 to 15 years we’ve had a real advancement in helping us understand exactly what those concentrations mean. Some of them are very meaningful, some of them aren’t. But I really go to single injection where you can give one single injection. (Dan) Right. (Mike) And that will see you through for a certain time period when you make the decision on whether or not that animal is recovered or whether it needs more therapy. And that’s one of the key, critical things we’ve talked about before that our producers need to do with the veterinarian is clearly understand how long after the administration of that antibiotic that decision needs to be made of yea, it helped them get better or it didn’t. And the reason I use single injection is we have some antibiotics that will work against the disease with a single injection that are actually almost unmeasurable in 48 hours. And we have some… (Dan) You mean in the body. (Mike) In the body, yea. (Dan) They’re cleared in the body. (Mike) They’re cleared… at least therapeutic concentration, there may be some residues. And we have some that work by single injection that you could measure concentrations out as long as 10 to 12 days. (Dan) Now, part of that is because they have different mechanisms of action. (Mike) Yea, and… (Dan) The duration versus concentration dependent. (Mike) Right, and some of these drugs work best by one big high hit, and then they can leave and some require a constant steady pressure on the bacteria and they need to be there awhile. And it’s the way, based on how they interact with the bacteria and the target. But what I… still when I go out in the field, I’m still thinking single injection or do we need multiple? And all that science rolls into whether you can give it once or you need to give it multiple times. But regardless of the mechanism for being able to give it once, again knowing when to stay yes, they need more or they don’t need more is the absolute critical thing for our listeners to understand. (Dan) Yea and that’s understanding and working with your veterinarian to understand how long the antibiotics… if you use an antibiotic that’s on board, in the animal at a therapeutic dose for 48 hours, you need to wait 48 hours before you introduce another compound. And if it’s on board for seven days, you need to know that you’ve given an antibiotic at four days… (Mike) Right. (Dan)…it could be harmful if they wrong compound is used at the time that you’re using one of these long acting antibiotics. (Mike) Cause some of them don’t like each other very much. (Dan) And that gets back to our cidal, static and mixing those types of drugs together. So working with your veterinarian to understand that sometimes you can do harm… (Mike) Being inventive isn’t always good. (Dan) Right. Well, we’re gonna take a break. When we come back from this message, we’re gonna wrap up with Dr. Apley talking about Antibiotics 101. And I’m sure we’re gonna have him back for a revamp on the course. Stay tuned.

(Dan) Hey folks, welcome back to Doc Talk. Dr. Dan Thomson and Dr. Mike Apley here from Kansas State University’s College of Veterinary Medicine. And Dr. Apley is a professor in clinical pharmacology and we’re talking about antibiotics and Mike we talked about static versus cidal antibiotics. We’ve talked about concentration dependent versus duration dependent antibiotics. So really two important decisions that veterinarians have to make when they’re helping make the decision on which drugs to use, but you know some of the things, oral versus injectable and spectrum of activity are two things I have circled that you know, just walk me through a little bit on the difference between the oral versus injectable. (Mike) A great example there are the tetracyclines, so everyone listening that works with cattle or hogs, understands there’s injectable and there’s oral versions. And in cattle if you look at the dose for long acting oxytetracycline injection, it’s nine milligrams per pound. Some have 13.5 milligrams per pound that’s given once. Then you look at the oral feed administration form and it’s 10 milligrams per pound per day. And you go wow, so they’re the same. Well, they’re not. Because the oral bio-availability of the tetracyclines is really very low. So, giving 10 milligrams per pound per day in the feed is no where near reaching the same concentrations in the animals, as giving nine milligrams per pound once that goes over three days or the 13.5 which goes a little longer. Because the concentration in their blood from the oral at roughly the same dose is about one sixth to one eighth the concentration that would be obtained by injecting them. So, it’s not the same and it’s very different. So, now especially as veterinarians are going to be required to authorize that feed use whether it’s now being an over the counter. That’s one of the considerations that veterinarians are gonna make is OK, is it appropriate to use this, which is gonna result in much lower systemic concentrations or do we need to inject with another tetracycline. So, the oral is… the same does given orally isn’t necessarily the same drug reaching the animal as… (Dan) And with some of the oral products too, I use the oral products quite a bit, but you know sick animals don’t eat, so that’s the other consideration. And now you’re working with animal behavior and so many other things. And a lot of times if I know the calf is on the end of the needle, I know they got it. But I gotta catch ’em too. (Mike) Well don’t take this wrong, as in saying that oral tetracyclines aren’t effective for some diseases and especially controlling clinical antiplasmosis. Those out there have herds with antiplasmosis challenges starting in August through probably a month after vector season, have to do something to control clinical disease and very low doses of oral tetracycline is just enough to keep that anaplasma organism from running off and being really harmful to cows and bulls. (Dan) Well thanks for being on the show today. Always great to have Dr. Apley here. Remember to work with your local veterinarian to develop your antimicrobial stewardship program for the your herd that he treats. If you want to know more about what we do here at K-State, you can find us on the web at www.vet.ksu.edu. I’m Dr. Dan Thomson and you’ve been watching DocTalk today. Thank you very much for joining us and I’ll see you down the road.

Closed Captioning brought to you by AgriLabs, the Perfect Pairing of Performance and Value.

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