The Moos Room™

[music] [cow mooing]
Joe Armstrong: Hey everybody, this is Dr. Joe Armstrong. Hopefully, you had a chance to listen to Episode 59 for you're now going to listen to Episode 60. This is part two of our time with Pam Ruegg and Erin Royster, and we're talking about treating non-severe clinical mastitis. We'll jump right into where we left off last time. Thank you for listening. Thank you for being here today. Enjoy the episode.
We've, I think, laid the groundwork here, but we really need to get into the specifics of pathogen-based treatment. Once we culture and we know what we have, now what? We said that there's not all that many cows that we know absolutely benefit from antibiotics, and then there's even fewer because there's some that aren't eligible. Let's walk through, okay, I've cultured and I've gotten the results. When do I treat and when do I not treat, which is probably just as important.
Pam Ruegg: I'm going to work through it from simplest decision to hardest decision. How about that? If you have a non-severe case of clinical mastitis that you get a nice milk sample from, and you cultured and you've got no growth, you should crack out the champagne because the prognosis for about 85% of those cases is really, really good. Most of those cases are culture negative because they've achieved spontaneous bacteriological clearance before you've seen the inflammation.
In those instances, no antimicrobial is often a really good decision. Those animals have faster return to milk, they have faster return to normal somatic cell count, and they have really low rates of recurrence. That's an easy, easy one, and that should be depending on herd characteristics, somewhere between 25% to about 45% of your cultures. Do you agree with that, Erin, about that proportion?
Erin Royster: Especially with your first statement, if they can collect a really good clean milk.
[laughs]
Joe: Right, that's what I was about to say.
Erin: If you're collecting good clean milk samples, yes, 25 to 40. If [unintelligible 00:02:20] 10 to 40.
Pam: Yes, exactly.
Emily: Collecting clean milk samples is a whole another podcast.
Pam: Exactly, Emily. The second easiest decision would be a gram-negative. If you've got gram-negative growth in a non-severe case of clinical mastitis, I would normally recommend no treatment on those. If you want to get a little more advanced on that, you can take a look at the cell count history of those cows because cell count history is a really nice clue as to if they have E. coli or a Klebsiella.
Our recent work showed those two pathogens behave very differently even when the clinical signs are identical, and that's the hard part on the gram-negative culture plates. If your herd where you're fairly confident you don't have a lot of Klebsiella, that no-treat decision is pretty easy. If you've got some Klebsiella, then I don't know what you do. [laughs]
Joe Armstrong: Well, I appreciate you being honest because that's right where I was in practice as well. Good.
Erin: This is a really common question, E. coli versus Klebsiella. First, how do you know whether you have E. coli versus Klebsiella? I have been telling people for years that you cannot go based on what the colony looks like on your plate.
Pam: Right.
Erin: People really want to believe that they can see that snotty Klebsiella and believe that it's there, and that's just not true. It's a coin flip if you're just using your eyeball in trying to figure out what it looks like in determining the difference. I like this because we have some data on this that somatic cell count history can be a good way and that's something that people have, that's data that a lot of herds have.
You can look at the somatic cell count history of the cow and say, we tend to have Klebsiella cases in our herd because we've done some diagnostic lab culture. We know we have Klebsiellas, so for this individual cow, I may not be able to tell that by looking at her culture plate, but I can look at her somatic cell count history and say, oh, she might be a Klebsiella, maybe I should do something different with her because we know the spontaneous cure rate for Klebsiellas is not as high as E. coli.
Pam: Nor is the treatment cure rate.
Joe: Right.
Erin: It's the second part that's really interesting. Now you have a Klebsiella, what should you do? I don't know.
Pam: There's a lot of complicating factors on Klebsiella and there's stuff that's not in that recent gram-negative paper that we didn't publish because we didn't have enough cases but I'm convinced is correct. There's a few things there. There was a big parody effect on our outcomes with Klebsiella, somewhat similar to Staph aureus. Younger animals appeared, and this was not statistically significant. Now I'm taking off my scientist hat and just putting on my clinician hat.
I looked at the data on our cases and I'm like, "Well I might try treating a first lactation animal that's only had a cell count high for a couple of months, it has Klebsiella." The other really complicating thing with the Klebsiella cases in that dataset we had is about half the cases were resistant to Ceftiofur. They had absolute resistance to Ceftiofur and it was a bimodal distribution, which infers that's an inquired resistance. They were either really resistant, really high MICs, or really low.
That's a clue that some of them are resistant. That's problematic, especially with that class of drugs which we need to be really careful with on farms. That's why I say I don't really know. I think that if you've got a Klebsiella, you've had some, as Erin said, diagnoses done in a real diagnostic lab and you see an E. coli case, it's got a long-term high cell count, maybe two or three months high because E. coli doesn't behave like that normally, and she's first lactation animal, you might want to try treating her once.
You'd want to use SPECTRAMAST on that cow, absolutely, but don't ever do it again if she doesn't respond because it's a pretty good clue that you're not going to be successful.
Erin: I like this because it's super practical. We have information that makes sense that we use with other pathogens like Staph aureus, like using [unintelligible 00:06:57] clinical mastitis and somatic cell count history to choose which cases we think have the best shot of treatment. It makes sense to apply those same rules to Klebsiella and make sure that we're practicing good antimicrobial stewardship, particularly because we are going to choose Ceftiofur, a third-generation cephalosporin for this one particular pathogen.
Pam: Right.
Joe: How do systemic antibiotics play into this?
Pam: Not at all.
Joe: Not at all, perfect. I love it.
Pam: This recent review that I did, I was trying to actually figure out in this review article the role of systemic therapy because these papers came from all around the world. There are some drugs available in other countries that have the actual ability to penetrate the mammary gland. We do not have access to any of those drugs in the US. We have, first of all, no products labeled for systemic administration, which means that any injection given to a cow to treat clinical mastitis has to be done under the direction of a veterinarian with a veterinary client-patient relationship.
Secondly, we have no evidence that any of the drugs that we can give can achieve an effective concentration in the udder. Thirdly, we have no clinical trials that show efficacy. At this point, for non-severe cases of clinical mastitis, I absolutely cannot recommend the use of systemic products in the US.
Joe: Again, if we can bold it, we'll bold it but that's the message. Keep that in mind. We've gone through no gross, gram-negatives with the caveat of Klebsiella. What's our next easiest decision?
Pam: Staph aureus. We probably don't want to treat Staph aureus, we want to cull those cows. Those are cows we do want to have a career change for. Those are gone. No treatment on those. With the exception of a cow here and there that you consult with a veterinarian none on the odds but mostly no.
Erin: Like your first lactation early days in milk heifer.
Pam: That you love for some reason.
Erin: Absolutely. Yes, right.
Joe: Oh, yes. There's definitely a non-economic component to some of this as well, so keep going.
Emily: Yes, I was going to say like your child's favorite show cow.
Pam: No, never keep them. They will transmit to all the other animals.
Erin: Call the parents [unintelligible 00:09:31]
[laughter]
Joe: I tend to agree with Pam on that, but at the same time, I'm not going to tell the kid that we're getting rid of his cow. We'll try first, and then we'll have that discussion later. Staph aureus, then what's next?
Pam: Then we get into this group of gram-positive pathogens that we used to assume were all coagulase-negative staff or [unintelligible 00:10:00] and streptococci. I think all of us have spent the last 10 or 20 years saying, that's the group we want to use the antibiotics on. That's been my mantra for years. We've just completed a trial. The trial wasn't quite as powered as much as we like because we had to stop data collection due to the pandemic. We were actively collecting data last March, but we have a fairly good-sized trial. We have 250-some cases, which is a nice size relative to other studies.
What we learned in that study is that when you use on-farm culture to identify gram-positive pathogens on modern dairy farms, you are coming up with a lot of gram-positive cocci that are not on product labels of intramammary tubes and have no efficacy data. I am growing a bit more cautious on my recommendations. I'm not ready to say we don't treat this group. I am absolutely not ready to say we don't treat this group. What I'm ready to say is some of these pathogens have high rates of spontaneous cure. Some of these pathogens don't cure at all. We need to do a whole bunch more work in this area.
I think it's important to recognize that things that grow on on-farm culture that we think are Straph, a lot of them aren't. While I think if you want to err on the side of caution, you would treat that group probably for minimal duration, but I'd say stay tuned.
Joe: You already said it because I was already ready to ask you, am I going to stop treating these gram-positive pathogens that I identify because of the wide distribution and some of the data from your study? I think it's comforting to me to know that we are still treating something. I think that's the hardest thing to get across to the farmer is that not treating, also sometimes the workers on the farm. Getting buy-in from everybody that we're going to see abnormal milk, we're going to do all these things and not treat, that's a tough buy-in sometimes.
What's the next step, Pam? How are we going to figure out? This seems like a huge, like a Pandora's box here that we're opening of how are we going to differentiate all these things? How are we going to do it quickly enough for it to matter? All these different things. How is that all going to play out?
Pam: Let me back up and just give a little description of what we did with these gram-positives. We had a non-treated control group, which is really unusual. We paid farmers for milk discard or for the potential of the animals. We paid them an honorarium for those cows. Then we had two, three-day treatments. One was PolyMast. One was three days of SPECTRAMAST, and one was eight days of SPECTRAMAST.
The first thing I'd say is we saw no difference in most of our important clinical outcomes amongst those groups. This is the first trial that has been done in that area. I never make broad-ranging recommendations based on a single trial, although we had four farms in that trial and the data is pretty solid. What I think we can say definitively today is you don't need long-duration therapy.
That's the easiest thing I think to implement right now. You can go with a short-duration therapy of any of the approved inter-mammary products right now for your treatment of gram-positives. If you have a history of a cow, again, I would use the same principles we've used for the groups of the gram-negatives and the no gross. If you've got a history of a cow that's a younger cow that's got a fairly low cell count prior to the case and you want to experiment with no treatment of gram-positives, experiment with your young cows who are otherwise healthy and in positive energy balance.
I would not recommend going to no treatment with older cows, cows with a history of a long-term high cell count, cows maybe in early lactation. I think the average days in milk on our clinical cases was pretty much 150 or 159 days or something. We're looking at mid-lactation cows on average in that population we enrolled. I think that's important too. I would say definitively, you don't need broad-spectrum drugs. You don't need eight days. Let's take baby steps toward improving our antimicrobial stewardship.
Erin: I was thinking about what I would say to a vet or producer after they heard about this graham-positive study that you did. Your takeaway's good. I like it. I came up with, one, go back to our case selection and think about looking at case history. Don't treat cows that have chronic mastitis, chronically high cell counts, or otherwise crummy cows.
The other part is, basically, even with the group of organisms that we thought we needed to treat to make a difference, we're probably overall not making as big of a difference as we think we're. Therefore, investing a lot of energy and money into treatment decisions is probably a bit of a waste of effort. We should transfer some of that to prevention because we know that prevention is way more effective.
Pam: That's a really good point, Erin. One thing I often start talks with to producer talks is treatment. The cost of treatment is always an economic loss. All your treatment dollars are economic loss. You're just trying to design a treatment that will lose you the least amount of money. Your dollars you spend on prevention are investments. They're not losses. They will translate into more income. I think that's a really important concept to understand, an investment versus a cost.
When you're looking at your treatment strategies for gram-positives, A, I think it's really important to do some culturing in a real diagnostic lab, especially a lab that has moldy so that you can know what's out there. There are farms that you can go to that do have a lot of strips. If you know that, I would recommend continuing to treat those gram-positives. What we learned in this study, and we're still delving into that, this is part of [unintelligible 00:16:57] PhD dissertation, is that on the four farms we went to, we had a lot of stuff that's not on product labels that grows on gram-positive media. There are no clinical trials for those bacteria.
Joe: Pam, I want to look a little bit in the future because we're talking about culture a lot. We're seeing sequencing becoming more and more and more popular and less and less expensive. Where does that start to come in, especially when we're talking about gram-positives and trying to differentiate between them?
Pam: We've sequenced actually a fair number of organisms just to play around with, and we're doing more of that coming up, but sequencing is really confusing. I think we're a long ways off. What you get with sequences is you see these base pair. You see places where the little DNA pieces have moved around and you sit there and think, well, does that matter or not?
It's just like these COVID variations. You've got the best scientists in the world looking at these different strains, and they're like, we're not really sure what that means. That's where we're at with a lot of these sequencing decisions on dairy farms. I think we're a long ways off from using that data.
Joe: I had a question and now it's gone. Oh, Bradley, I'm trying to channel my inner Bradley. Bradley loves organic farming and runs both a conventional and an organic farm side by side. You've repeatedly said not antibiotics but antimicrobials when you're talking about infusions. Does this all apply to some of our organic options as well when we're talking about tubes on the organic side?
Pam: One of the motivating factors for me in doing some of these clinical trials was, at one point, this is probably 10 years ago, I had two big studies going on. One study was L. Oliveira study where we went to 52 large Wisconsin herds, and we just figured out what they were using to treat mastitis and what some of the outcomes were. At the same exact time I had that going on, I had a study going on where we enrolled 200 organic farms in a 100-matched herd size conventional farms and collected a ton of information on disease and treatments and such.
I had little farms, organic farms, and big conventional farms we're getting data at the same time, and I'm looking at outcomes and stuff and I'm not seeing a lot of difference. I'm like, we really have to look at this, but I want to really stress that there is zero evidence. Absolutely zero evidence that any of the botanical therapies, any of the herbs, any of the tubes that are sold and marketed on organic farms, there is zero evidence of efficacy. Absolutely zero.
Beyond the evidence of efficacy, I'll say we collected data on hundreds of farms, and what we learned is there was huge variability in what people used, and people would change what they use. I think farmers are really smart and clever. If there was a therapy in the organic world that was absolutely efficacious without any studies by people in the university, they would figure it out and they would all use the same thing, but they don't do that.
I think there's no practical in-the-field evidence that there's an overriding efficacious organic therapy and I think there's no scientific evidence, and I have absolutely no compunction saying that organic dairy farmers have no available treatments for mastitis. That said, the organic farmers, being as clever as they are, focus a lot on prevention, and they do a lot of strategies like drying off hoarders and culling cows and using those cows that allow them to market high-quality milk.
Joe: I know Bradley might be a little devastated that you're so emphatic that there isn't an option for treatment, but we'll set him straight when he gets back. We talked about organics.
Erin: Can I ask a question, Joe?
Joe: I guess so.
Erin: I think that we have covered a lot of very practical territory for our veterinarians and producers who are listening. I want to ask one more. You've given vets a lot of great advice about how to set up their treatment protocols on dairies. What should veterinarians be monitoring to gauge treatment success on a dairy?
Pam: First of all, they should be monitoring compliance with the protocols that they're asking them to follow. That's really an important thing. Second, if they are doing on-farm culturing, they should be engaged in that and monitoring actually a couple of key quality control things. Erin, you mentioned earlier the percentage of culture-negative plates. That's a really important QC factor.
You got to see if they're doing culture-based therapy, are they doing it right? If they're given protocols to follow, are they doing that right? I think that's fundamentally the most important things is, are the protocols being followed? If the protocols are being followed, then I think you want to look at the percent of animals who have cell counts that return to normal or healthy levels by about six weeks.
I think you want to look at recurrence, and again, not 100% correlation or association with treatment efficacy but really important to understand the system that you're treating in. I think you do want to have some idea of the number of days of milk discard because that's a huge indicator of compliance with a protocol, but I think that's about all you can monitor. You can look at culling rates but culling rates are driven by so many other factors. Culling rates are often a pile-on effect. She's not pregnant, she gets mastitis, she's lame, she's got to go.
Erin: Do you have benchmarks for recurrence and percent culture loss?
Pam: For recurrence, again, it's going to be highly pathogen dependent. If you've got no gross, you're going to have about a 5% to 10% recurrence rate. If you've got a huge rate of exposure, say a manure solids herd, you could be up to a 40% recurrence rate. The data we have, which we've collected on a bunch of herds, shows an average recurrence rate is about 20%, and that's after 14 days. You'd want about 85%, 90% of those cows to be back in the milking herd or eligible to be back in the milking herd by the end of their milk withholding period, somewhere around day seven to eight.
Cell count, you've got to know your pathogen type, but you'd probably want -- I'd have to look at that but 70%, 75% of those cows to be headed toward a healthy level.
Joe: I think compliance is always something we struggle with and trying to do that from the veterinary side, but then also if you are a farmer with employees, doing that on that end as well, making sure that on your end, the protocol is being followed that you've laid out for employees to follow because it drifts whether it's miscommunication or something else going on.
Then I think looking at these same things whether we're looking at the percent of somatic cell normalizing or returning to previous levels, recurrence rates, days of milk discard, any of those things can also point to some of those other things we talked about on the farm. Maybe the protocol is being followed to perfection, but there's something else that's adding into that complexity, whether it's Klebsiella or some of these other bugs that we've talked about already.
I think even just monitoring those to make sure that you have your farmers' back and you're watching out for them as well. Last call for questions. Emily, any last fan girl moments? Anything?
[laughs]
Emily: No, I've been quiet this episode. I'm just really star-struck.
[laughter]
Joe: Good deal. Erin, anything that you need?
Erin: No, I got all the good stuff. That was really fun, Pam. Thank you.
Pam: It was fun. I really enjoyed this.
Joe: Oh, good. I would welcome you to come back anytime, Erin, we'll have to talk a little more. Pam, you're welcome to come back anytime.
[laughs]
Emily: Erin, you're welcome to come back anytime too. This isn't the Joe show.
Joe: Emily is the boss, so.
Pam: I don't know. You've got to correct that University of Minnesota Madison, though. [laughs]
Joe: I don't know where that came from. Maybe it was just this hope that you'd come to Minnesota instead. I don't know what it was.
[laughter]
Emily: Come to us.
Erin: We would love to be able to claim Pam.
Joe: Absolutely, 100%. All right, with that, we'll wrap it up. Thanks again to Pam and Erin for being here. Hope everybody enjoyed this episode. If you have questions, comments, scathing rebuttals, which there might be after today to anything we said, please send them to themoosroom@umn.edu.
[music]
Emily: That's T-H-E-M-O-O-S-R-O-O-M@umn.edu.
Joe: If you want more information about anything else we've talked about related to milk qualities today, definitely jump on YouTube and search for Pam's YouTube channel, UW Milk Quality.
Erin: If you're interested in mastitis treatment, we are going to be offering a mastitis treatment short course as part of our Minnesota Dairy Health Conference webinar series in the spring and summer. You can find more information about that at dairyhealthconference.umn.edu
Joe: Pam, anything else you want to plug?
Pam: You can follow me on Twitter, I'm @topmilk.
Joe: @topmilk, I will do that right now for The Moosroom because we're on Twitter as well. Thank you for listening, everybody. We really appreciate it. We'll probably have these two back in the future. I don't think we can avoid it at this point.
Erin: Awesome.
[laughs]
Joe: All right. Bye, everybody.
Emily: Bye.
Pam: Thanks, guys.
[cow mooing]
[00:27:40] [END OF AUDIO]

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