The Clinical and Laboratory Standards Institute (CLSI) has updated their main veterinary testing standards document: VET01SEd7E Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals, 7th Edition. Check out earlier posts for an overview of the relevant changes, and more specifics about the standards for staphylococci and chloramphenicol.

Today’s topic is about fluoroquinolones, a drug class with which I have a love-hate relationship. They’re great drugs, I just wish we’d massively decrease how much we use them, so they can keep being great drugs for animals and people for a long time. If we’re going to use a drug class like fluoroquinolones, we need to use it right. The news CLSI guidance will help with that, once we figure out how to get it actually rolled out.

There are three major changes in the latest update regarding fluoroquinolones:

  • changes in breakpoints for susceptible, intermediate and resistant bugs
  • introduction of dose-dependent breakpoints
  • removal of disk diffusion breakpoints

Changes in breakpoints

The mean inhibitory concentration (MIC) breakpoints for fluoroquinolones have been lowered, meaning some bacteria that would have been reported as susceptible using the older breakpoints will now be reported as resistant. Fluoroquinolones will therefore be an option in fewer cases, but when they are an option (i.e. when a bug is reported as susceptible), we should be more confident that they will be effective.

Susceptible, dose dependent (SDD) breakpoints

A major change in this update of the lab standards is the introduction of susceptibility reporting that is based on dose. Since we can safely increase the dose of fluoroquinolones quite a bit in most situations (enrofloxacin in cats being the main exception, and probably also any fluoroquinolone in very young animals), it makes sense to consider the dose when determining susceptibility. If we can get 2X or 4X the amount of drug at the site of infection, we can sometimes treat bacteria that would not have been inhibited with normal dosing.

A quick rundown is below.

Here’s a quick comparison of the changes regarding enrofloxacin for staphylococci and Enterobacterales in dogs:

GuidelineSusceptibleIntermediateSDD 10 mg/kgSDD 20 mg/kgResistant
6th edition< 0.5 ug/ml1-2  > 4
7th edition<0.06 ug/ml 0.120.25> 0.5

As with chloramphenicol, we have to figure out how to deal with this now, as labs make the necessary changes to their testing and reporting protocols.

  • A big barrier to this is the limited range of drug concentrations that most labs test. If the main commercial plates used by the labs don’t test low enough concentrations of the antimicrobials, we can’t interpret the results easily using the new guidelines.

In the interim, we need to look at the MIC values on the lab reports, not just where it says “S,” “I” or “R” (since S, I and R may be based on the old guidelines).

For enrofloxacin:

  • If the MIC is >0.5 ug/mL, the bug is resistant. Don’t use this drug.
  • If the MIC is 0.25 ug/mL, the bug should be susceptible if we use a dose of 20 mg/kg.
  • If the MIC is 0.12 ug/mL, the bug should be susceptible if we use a dose of >10 mg/kg.
  • If the MIC is <0.06 ug/mL, it’s susceptible at >5 mg/kg (although in dogs, I’d rather not go below 10 mg/kg and in cats, I basically never use enrofloxacin because of safety issues).

However, if the lab reports MICs of <4, <2, <1 or <0.5 ug/ml, you can see we’re kind of screwed. We need to know that the bug has an MIC of no greater than 0.25 ug/mL, and none of those higher MIC breakpoints tell us that clearly. For any of those, the bacterium could be susceptible, susceptible but only at a higher dose, or resistant. I would not use enrofloxacin in those cases if I can’t tell what, if any dose, will be effective.

Marbofloxacin is pretty similar. The new breakpoints are lower, and they’ve incorporated one susceptible, dose-dependent (SDD) breakpoint. They also removed the recommendations for disk diffusion testing (one of the other methods for antimicrobial susceptibility testing, vs broth microdilution).

GuidelineSusceptibleIntermediateSDD 5.5 mg/kgResistant
6th edition< 12 > 4
7th edition<0.125 0.25> 0.5
  • If the MIC is >0.5 ug/mL, the bugs is resistant. Don’t use this drug.
  • If the MIC is 0.25 ug/mL, the bug should be susceptible if we use a dose of 5.5 mg/kg.
  • If the MIC is <0.125 ug/mL, the bug should be susceptible at a dose of >2.75 mg/kg.

If the lab reports MICs of <4, <2, <1 or <0.5 ug/mL, we don’t know if if the bug is actually susceptible or resistant (so I’d stay away from this drug to be safe).

What about cats?

For cats, the breakpoints have changed as for dogs, but there are no susceptible dose dependent (SDD) breakpoints. Presumably that’s because we don’t have enough data to determine SDD breakpoints for cats. For enrofloxacin, it’s a non-issue for me, since I’d never use 10 or 20 mg/kg of this drug in a cat. For marbofloxacin, it’s a reasonable consideration since we can safely use higher doses. I wonder whether we’ll see labs report things for cats as they do for dogs. It’s not unreasonable, it just has less supporting data.

Yesterday, I wrote a post about a new version of CLSI’s Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals. There are some major changes in this update, and I sympathize with the diagnostic labs that now have to update their testing and reporting. It won’t happen overnight, because some may need to develop different testing panels to account for some of the different breakpoints, and they’ll need to change their reporting systems.

While we want to push labs to update their methods and reporting ASAP, we still have to manage patients in the interim. My next few posts will explain how I’ll be looking at interpretation of antimicrobial susceptibility testing results in the meantime.

I’ll start with chloramphenicol and staphylococci in dogs. Our typical methicillin-resistant Staphylococcus pseudintermedius (MRSP) tends to be resistant to multiple antimicrobial classes beyond beta lactams, and therefor has limited treatment options, so chloramphenicol susceptibility often gets included in reports for this bug.

The old breakpoints for chloramphenicol and staphylococci in dogs were:

  • Susceptible < 8 ug/mL
  • Intermediate 16 ug/mL
  • Resistant > 32 ug/mL

The *new* breakpoints for chloramphenicol and staphylococci in dogs are:

  • Susceptible < 2 ug/mL
  • Intermediate 4 ug/mL
  • Resistant > 8 ug/mL

I don’t think the intermediate category means much here, since chloramphenicol isn’t a drug for which we can safely increase the dose. So, practically speaking, the bacterium must have an MIC < 2 ug/mL for chloramphenicol to have a chance at being effective.

One big problem the labs will have is that at least one of the plates commonly used for susceptible testing of bacterial isolates from dogs won’t be able to differentiate susceptible from resistant to chloramphenicol based on these new guidelines, because the lowest concentration it contains is 8 ug/mL of chloramphenicol.

  • If there’s no growth in the 8 ug/mL well, then the bug was inhibited at that concentration and we know the MIC is 8 ug/mL or lower; but we won’t know if the true MIC is 8 ug/mL (resistant), 4 ug/mL (intermediate) or < 2 ug/mL (susceptible).
  • If the bacterium grows in the 8 ug/mL well, then the MIC is clearly greater than 8 ug/mL, meaning the bug will be clinically resistant to chloramphenicol.

Labs will need new plates with (at a minimum) 1, 2, 4 and 8 ug/mL chloramphenicol wells.

So, what do we do in the interim? We have to look at lab reports to see if an MIC is reported.

If your lab reports MICs:

  • Look at the MIC, not just S/I/R category.
  • If the MIC is 4-8 ug/mL, the bug is resistant, even if the report still lists it as “susceptible.”
  • If the MIC is “<8 ug/mL” or “<4 ug/mL,” we have no way to tell if the bug is resistant or susceptible. Since a large percentage of S. pseudintermedius from dogs will have MICs that fall in the 4-8 ug/mL range, odds are pretty good that treatment will fail if all we know if that the MIC is <8 ug/mL, so I’d consider it resistant to be on the safe side (see examples below).

If your lab does not report MICs:

  • I’d consider the bug resistant to chloramphenicol, since most staphylococci are resistant to this drug.
  • Ask your lab to start reporting MICs. As we learn more and get better guidelines, MICs are becoming more useful, and therefore important to include on antimicrobial susceptibility reports.

Diagnostic testing is a cornerstone of veterinary medicine that helps us optimize patient care, but there’s a lot of science behind it that people often forget. We collect a sample, send it off for testing and magically get the results, often without putting a lot of thought into what happens at the lab. Labs (should) follow standard guidelines for performing tests of all kinds that are developed to help ensure they provide relevant and accurate results. As with most things (medicine or otherwise), guidance changes over time as we learn more and as new issues are identified. Keeping up with those changes is critical.

The Clinical and Laboratory Standards Institute (CLSI) is an organization that sets standards for microbiology testing in humans and animals. The standards are updated regularly, with some updates being more impactful than others. Hot off the presses (just today!) is the latest update to the main veterinary testing standards document: VET01SEd7E Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals, 7th Edition. This is a major update with some changes that will have significant impacts on how lab results are reported and interpreted, including changes to some of the interpretive breakpoints for susceptibility of certain bacteria to specific antimicrobials.

A core part of antimicrobial susceptibility testing is determining the minimum inhibitory concentration (MIC) of an antimicrobial for a particular bacterial isolate. The MIC always needs to be interpreted in the context of each patient in the context of how much of the antimicrobial we can expect to get at the site of infection when the animal is treated. A bug could be susceptible to low concentrations of a drug (low MIC), but if drug levels we get in the infected tissue are even lower, it might not be effective. Conversely, a bug might has a fairly high MIC, but if the drug reaches the site of infection at even higher levels, it might still work.

Breakpoints consider how much drug is required to inhibit the bacterium and how high the concentration of drug is expected to reach in the body. The breakpoint is the MIC where things tip between susceptible and resistant (or susceptible, intermediate and resistant).

New “susceptible, dose dependent” (SDD) category

One major change in the updated lab standards is that they now provide guidance for a susceptible, dose dependent (SDD) category for certain bug/drug combinations. This goes beyond the familiar susceptible, intermediate or resistant classification. The SDD category considers the potential to use higher drug doses and how that impacts the bacterium’s susceptibility. That’s relevant for some drugs where we can use higher (but still reasonable and safe) doses.  

Take for example the guidance regarding enrofloxacin and both staphylococci and Enterobacterales (i.e. E. coli and relatives) in dogs.

The previous version of the lab standards said:

  • MIC <0.5 ug/mL: susceptible
  • MIC 1-2 ug/mL: intermediate
  • MIC >/=4 ug/mL: resistant

Two things have now changed. One is that the breakpoints have been lowered a bit. The other is that they’ve come up with dose-dependent interpretive breakpoints:

  • MIC <0.06 ug/ml: susceptible at a dose of 5 mg/kg once a day (FYI I pretty much never use a dose that low for enrofloxacin because of concerns about efficacy and development of resistance)
  • MIC 0.12 ug/ml: susceptible at a dose of 10 mg/kg once a day
  • MIC 0.25 ug/ml: susceptible at a dose of 20 mg/kg/day
  • MIC >/=0.5 ug/ml: resistant

The lower breakpoints mean we’ll see a lot more of these bugs reported as resistant to enrofloxacin. The dose-specific guidance will help figure out when we can still use enrofloxacin to treat some of these middle-ground MIC bugs, and hopefully reduce ineffective use of this important antimicrobial.

Communicating this to veterinarians will be a challenge, since it’s a completely new concept for most.

Other breakpoint changes

Some other breakpoints have changed in addition to the reduction of the enrofloxacin breakpoints mentioned above. One is the reduction of the susceptible breakpoint for chloramphenicol and staphylococci in dogs from <8 ug/ml to <2 ug/ml. Bacteria with MICs of 4-8 ug/ml previously would have been called susceptible to chloramphenicol, but now will be reported as resistant. That’s relevant because there are a lot of staphylococci with MICs in that range, and we now consider them non-susceptible to this drug. So, we’ll see a lot more reported chloramphenicol resistance.

More species-specific breakpoints

The updated standards have also added numerous species-specific breakpoints. Unfortunately we don’t have breakpoints for all bug/drug combinations in every species. In these cases, we either have no guidance or we extrapolate from humans or other animals (better than nothing, but not ideal since there can sometimes be big differences between species). Over time, as more data become available, we eventually get to the point where we can make more specific recommendations.

Urinary breakpoints

Another subtle but important change is modification of how site-specific breakpoints are reported. Most of these are based on serum drug levels, since that’s what should be present throughout most of the body, and we tend to have the most data about serum levels. However, we know that some drugs are excreted at high levels in urine, and those high levels can make bugs that are resistant to a drug in serum susceptible to it in urine.

For that reason, there are separate serum and urine breakpoints for some drug/bug combinations (e.g. E coli and amoxicillin). Urine breakpoints are higher because more drug ends up in the urine and will be able to inhibit some bacteria that would tolerate the lower concentrations of drug in other parts of the body. Previously, this was called a “UTI” (urinary tract infection) breakpoint. The problem was urine levels are only relevant for lower urinary tract infections (cystitis), not upper urinary tract infections (e.g. pyelonephritis). For an infection in the kidney, we need to rely on the drug that’s in serum, not in urine, so the UTI terminology has lead to confusion and misreporting. Now it’s clearer as the the updated standards call those breakpoints “(lower) urinary tract (ur).“ Hopefully that will result in fewer pyelonephritis samples being interpreted with urine breakpoints and leading to suboptimal antimicrobial treatment decisions.

Labs vary in how quickly they make changes when these standards are updated. Some are on the ball right away. Some are really slow. Some never adopt all the guidelines. (I saw a lab report yesterday from the US using an old guidance that was changed 10 years ago, leading to a bad treatment choice.) Veterinarians asking labs if/when they’re going to adopt the changes may help spur them on. It’s a hassle for labs to make the changes and communicate why things are now different in the lab reports, but it’s important to get this done for obvious reasons.

I spend a lot of time talking about antimicrobial misconceptions and dogmas. They are a big issue, because they often lead to unnecessary or excessive duration of antimicrobial use, use of more invasive routes of administration (e.g. intravenous over oral), or use of higher-tier antimicrobials than necessary.

I’ll just address one of these misconceptions today: Doxycycline should be avoided in young growing animals because of teeth staining and bone development.

Nope.

The concern about using doxycycline in young animals relates to calcium binding. Tetracycline and some of the older drugs in this class have substantial calcium binding and use of some tetracyclines has been shown to impact the development of teeth in various species, including dogs. It’s even sometimes used in wildlife rabies vaccine baits as a way to help determine if an animal ingested a bait when it was younger, because the tetracycline will cause detectable staining of the teeth.

Doxycycline is different. It doesn’t bind calcium to the same degree as other drugs in this class, so we can’t assume that what happens with other tetracyclines also applies to doxycycline.

Staining of teeth is a major concern in humans, so we can look there for some guidance. They’ve had the same dogma (i.e. avoid doxycycline in kids) for decades, but it’s been challenged and efforts are underway to refute it.

  • A review and commentary about kids and malaria stated, “It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age” because it is “a cheap drug with a broad therapeutic spectrum and very little evidence of serious adverse events.”
  • The American Academy of Pediatrics states “Although data are limited, evidence does not support dental staining as a consequence of doxycycline use in young children.” They recommend doxycycline for a variety of conditions in young kids, particularly tickborne diseases.

So, while we’re lacking data for dogs, information from other species shows that we shouldn’t be concerned about staining teeth or related effects in young animals, and we should therefore use doxycycline when it’s indicated even in young patients, as it is a lower-tier, safe and effective antimicrobial.

Unsubstantiated (or clearly disproven) dogmas persist in medicine (human and veterinary) and they’re really hard to address. However, we have to try to address them because they can cause harm.

This may be my last update on this topic in the short term (unless things change, of course).

The good news:

The bad news:

  • Well, it’s not really bad news, but we still don’t know what actually happened. That’s far from surprising, because with waxing and waning endemic disease conditions like CIRDC, we rarely have a clear picture of what happened and why.
  • Everything for me continues to point to a gradual increase in the rate of infectious respiratory disease in dogs over the past couple of years, with the usual intermittent local and regional peaks and valleys. This year’s issues were probably somewhat higher peaks overlaid on a higher baseline, making the issue more obvious and drawing more attention.

What was the cause of the increased cases of CIRDC?

I’m sticking to “the usual suspects, doing their usual thing, just at higher rates.” There’s been a lot of investigation looking for new pathogens and, as far as I know, nothing convincing has come to light. Given the number and quality of the research groups that have been looking, it’s pretty convincing that we don’t have a specific new pathogen that’s caused an outbreak of disease in dogs across North America.

What do we do now?

As with any outbreak, we try to learn some things from the experience:

1. Surveillance

This situation was a reminder that we don’t have a good surveillance system in place for CIRDC (or most other companion animal diseases). There’s no easy fix for that, especially with no money, so we need to continue to try to leverage the information that is available to better understand disease patterns. We need to do that on an ongoing basis, not just when there’s concern about increased cases, because when we’re concerned about an outbreak, we need to know the normal rates of disease to put things into context.

2. Vaccination

While we only have vaccines for a few of the important causes of CIRDC (Bordatella, parainfluenza, influenza), they are good vaccines, and we need to optimize their use in dogs that have a reasonable risk of exposure and/or a higher risk for severe disease.

3. Thinking about severe disease

The risk of severe disease in some dogs during outbreaks doesn’t get as much attention as it should; hopefully we’re changing that. In most dogs, CIRDC is a short term, self-limiting problem that’s fairly mild, just like upper respiratory infections in people. However, some dogs get really sick, and some even die. We can’t predict every dog that will have a severe outcome, but we know that there are groups that are at higher risk, particularly older dogs, dogs with pre-existing heart or lung disease, and brachycephalic dogs (i.e. flat-faced breeds). We need to think about minimizing exposure and maximizing vaccine coverage in these groups.

We also need to get people thinking about function over appearance in dogs they are breeding and buying. There is currently a disturbingly high number of anatomically disastrous dogs out there, because people have bred reasonably-functional brachycephalic breeds into extremely flat-faced dysfunctional dogs that have myriad respiratory issues, even without infectious diseases to complicate the situation (see the pictures below). As the French bulldog has shot to the top of the list of the most common breeds in the US, we’re going to see more dogs die from respiratory disease. Not all Frenchies are a mess, but there are enough of them that we see infectious and non-infectious complications in them all the time.

The recent situation with CIRDC also might get people thinking more about their dogs’ social networks and risks, and how to minimize those while having limited impacts on important or enjoyable aspects of dog ownership. We’ll be doing some work on dog social networks later this year, so stay tuned.

Image from: https://pedigreedogsexposed.blogspot.com/2017/08/the-frenchies-that-win-by-nose.html

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I’ll take a break from writing about widespread canine infectious respiratory disease complex (CIRDC) in North America to talk about a single case of a rare disease in a dog. Wageningen Veterinary Research has reported a case of Bluetongue infection in a dog in the Netherlands, a disease of significant consequence to livestock that’s recently been found again in the country.

Bluetongue is a viral disease caused by the unoriginally named bluetongue virus (BTV), which is endemic in many parts of the world, especially tropical and subtropical countries. However, a lot of countries put in significant effort to control this virus and maintain disease-free status, because it has major impacts on food animals. The infection often kills sheep, and while it doesn’t usually kill cattle, infection can cause a major drop in milk production. A single case of bluetongue in a previously disease-free country can result major livestock export restrictions. The Netherlands managed to control bluetongue since their last outbreak in 2007, but it was found again in the country earlier this year; based on the strain, it’s suspected the virus may have been imported from Italy.  

The bluetongue-affected dog in this report was a 3.5-year-old pregnant dog from a Dutch dairy farm. The dog had severe signs of illness, including shortness of breath, pulmonary edema, severe emaciation and lethargy. It’s interesting that someone considered bluetongue and tested the dog, especially since the disease wasn’t known to be present in cattle on the farm, though it was subsequently identified in two cattle after the dog’s diagnosis. Thanks to an astute vet and access to testing, a diagnosis of bluetongue was made through detection of BTV by PCR. Not surprisingly, it was the same strain of BTV that’s been circulating in sheep and cattle in the Netherlands.

There’s no mention of whether the dog survived and/or if it was treated. For something like this, we’d be focusing on supportive care and treating the consequences of the infection, while the dog hopefully fought off the virus itself, since we don’t have a specific antiviral treatment for BTV (or at least not one that we know is safe and effective in a dog).

This isn’t the first case of bluetongue in a dog, but it’s a very rare diagnosis. Interestingly, most of the reported canine cases have been in pregnant dogs. We don’t know why that is, but it could be for a number of potential reasons, or a combination thereof, including:

  • Just a coincidence
  • Greater likelihood of testing a sick pregnant dog
  • Increased susceptibility of dogs to infection during pregnancy

How was the dog infected with BTV?

Livestock-to-livestock transmission of BTV is mainly by biting midges (little insects), so the virus can move with infected sheep and cattle, infected midges (blown off course by storms or hitching a ride in a vehicle), or contaminated raw food items that somehow end up being fed to livestock (e.g. food scraps).

How this dog was infected isn’t clear. Contact with or ingestion of colostrum, fetal fluids or fetal membranes, raw meat or blood from an infected ruminant are considered the most likely routes of transmission. However, spread by infected midges can’t be ruled out. This dog lived on a dairy farm, had direct contact with cattle and their environment, and may have had access to high-risk tissues like placentas, so there were a variety of potential sources of exposure.

Does/did this dog pose a risk to other animals?

Presumably not. It’s assumed that dogs are “dead end hosts” for BTV. Dead end hosts can have serious disease but usually don’t produce or excrete enough virus to pass infection on to others. But that is an assumption here, and especially with a rare infection like BTV in a dog, we can’t have complete confidence in assumptions.

Does this case change anything in the big picture?

Probably not much. It’s a reminder of the unpredictability of infectious diseases, the need to consider the whole human/animal/environment ecosystem (versus having tunnel vision about certain species), and that spillover of infections from the main host to others probably occurs a lot more than we recognize for a wide range of infectious diseases.

No, I’m not talking about a need for Facebook for Dogs. I’m talking about the interaction and contact networks that dogs have, which are important for understanding and mitigating infectious disease risks. Let’s use my dogs as an example.

Dog 1: Ozzie

  • PITA (pain in the…) 1 year old Labrador.
  • Healthy, young, low risk for severe respiratory disease.

Dog 2: Merlin

  • 12 year old Labrador with chronic lymphoid leukemia who’s been on chlorambucil and prednisone for close to 2 years.
  • Otherwise healthy (for an old dog with leukemia), but presumably at higher risk for severe disease should he get a respiratory infection.

Ozzie and Merlin’s normal social network:

Their social network is pretty small. It’s predominantly just the two of them. We live in the country and they have very few random encounters with other dogs. They go for walks around our property and sometimes at the local agreement forest, so there’s always some chance for an encounter with another dog, but that’s a rare occurrence (and direct contact with another dog would be rarer still). Every week or so, Heather takes them for a walk with a friend and her dog, who has a similarly cloistered lifestyle.

They have few contacts with other dogs, the limited contact they have outside the household is a known, regular contact that’s low risk. Their risk of exposure to an infectious disease is pretty low (but never zero).

So the cost:benefit calculation is easy for me here. I don’t see a need to or benefit of disrupting their social network based on the current circulation of canine respiratory pathogens. Their network is small, low risk and the contacts are beneficial (for both the dogs and people). If one of the dogs was sick, I have no doubt any visits would be cancelled.

The “holiday effect” on their social network:

Here’s where things get more complicated. When we visit Heather’s family and the whole gang is there, it’s a bit of a gong show. We have Ozzie and Merlin, plus Maggie (adult Golden Retriever), Otis (adult behemoth of a Bernese Mountain dog) and Charlie (adolescent Labrador). That’s actually less than it could be, because Phoebe doesn’t make the trip… probably her own good as a small dog in the otherwise big dog frenzy). Otis and Charlie are from separate households in the same area of the US.

So, we have five dogs from three cities in two countries. They’re all well cared for and none have high risk lifestyles, but Otis and Charlie add a lot of unknown factors to the mix.

Is this a higher risk situation than our normal one? Yes.

Is it particularly high risk?

  • Probably not. It’s short term contact with a known but geographically distinct group of dogs.
  • We know the health status of the dogs and, as far as I know, none of them have any high risk exposures.
  • If there was rampant canine infectious respiratory disease (especially a new pathogen or severe disease) in the area from where any of these dogs came, I might reconsider getting them all together, but that would be case-by-case, since there are important family benefits of getting together (including the dogs).

Last summer’s social network

We rent a cottage for a couple of weeks every year. This year, we realized that “Ozzie + 24 hours at a cottage = not a lot of relaxation.” So, he went to a local day care for part of the day (a tired Ozzie is a much more enjoyable Ozzie). It was a typical day care, with about 20 dogs tearing around a compound. It was great for him, great for us, but absolutely higher risk for spread of respiratory disease, because it involved a lot of dogs that we know nothing about. It was a good day care and they required kennel cough vaccination, which reduces some of the risk, but doesn’t eliminate it.

So, Ozzie got a Bordetella / parainfluenza / adenovirus vaccine, and a lot of potential exposure. Merlin and the rest of us got a break from Ozzie, and we accepted the added degree of risk.

I didn’t give Merlin a kennel cough vaccine, although I considered it. Since he’s higher risk for severe disease, my threshold to get him vaccinated is lower, and it would have been reasonable to do to protect him in case something broke through Ozzie’s vaccine and he brought it home. This summer, if we’re in the same situation, I’d assess Merlin’s health status and the disease status, and decide whether or not to vaccine him too (I’d probably lean toward vaccinating him now).

The cost:benefit calculation was quite different here:

  • We greatly increased our dogs’ social networks and therefore risk of exposure to infectious diseases. However, my risk assessment deemed it worthwhile, for both the dogs and us.
  • If things were going off the rails from a disease standpoint, Ozzie wouldn’t have gone to the day care, dropping our risk back down to baseline.

There’s no standard formula to assess risk and what’s tolerable. We can’t take “x” number of contacts and “y” situations and come up with a magic number. Well, I guess we can, but it’s not going to be useful. However, sketching out a dog’s social network is useful to visualize the risks that are present and to assess each one.

  • Sometimes, you might say “that contact is not really important, it’s high risk and I can change things to avoid it.
  • Sometimes, you might say, “that’s a risk we have to take.

If you need to send your dog to day care to go to work, send your dog to day care. Just pay attention to where it is.

If you’re going on vacation, you may need to board your dog. If it’s a high risk dog and a high risk area, you may still have no choice, as a boarding kennel might be the best option. However, you might also be able to find a smaller well-run facility, in-home care or a willing friend to take your dog. There are often other options if you know where to look, and no one-size-fits-all solution.

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There’s still not really a lot to report with the current canine infectious respiratory disease situation in North America, which is probably good news. As ever, we’re largely flying blind because we have no coordinated surveillance for canine infectious respiratory disease, so we’re try to figure out as much as we can through a variety of sources.

Current status:

The hype is dying down. We’re seeing a far fewer reports of disease in dogs, and I’m getting fewer calls from veterinarians. The question is whether that’s because there’s less disease, or because people have gotten bored with reporting or have simply adapted to the current situation. The news cycle is pretty short, as are attention spans, so in the absence of fairly dramatic changes, social media and traditional media usually move on fairly quickly. My somewhat educated guess is that we still have an elevated baseline level of canine infectious respiratory disease complex (CIRDC)(which has been gradually increasing over the last couple of years), and some local outbreaks (as we always have), and decreasing rates of CIRDC in places that reported higher numbers this past fall. Those are all things we expect with the normal waxing and waning of endemic disease.

Where is this disease present?

CIRDC is everywhere, as always.

I get a bit annoyed seeing reports about “the disease” being present or absent in a particular area or those that try to give it a new name like “atypical CIRDC.” Canine infectious respiratory disease has been around as long as dogs have been around. Various respiratory viruses and bacteria are circulating in the dog population all the time, everywhere. When people ask “is it here?!” they’re really referring to an increase in CIRDC (or an increase in awareness of it), not introduction of some specific pathogen. Maps showing where the disease “is” cause confusion, and they’re purely made up.

Increased rates of disease absolutely occur in different areas at different time. When that happens, sometimes it’s missed, sometimes it’s high profile. Almost invariably, rates come down again after a few weeks, as things revert to normal.

Is there a new “mystery virus” causing disease in dogs?

Many good laboratories are doing deep sequencing to look for any new pathogens. The longer we go without anyone reporting something potentially relevant, the less likely it is that something new is involved. It’s possible that (but would be really disappointing if) a laboratory has found something they’re not reporting, but given the number of laboratories that are working on this, if there was a widespread new virus, I’m pretty sure we’d know by now.

My theory is still that the increase in CIRDC is being caused by our regular respiratory pathogens (e.g. canine parainfluenza virus, Bordetella bronchiseptica, canine respiratory coronavirus, canine pneumovirus, Mycoplasma) doing their regular things, just at higher levels in some areas.

What about that weird Mycoplasma-like bug from the laboratory in New Hampshire?

Not much new has been reported on this finding either. It’s good that they’re still working on it, but we’re not hearing similar reports from other laboratories, so it’s probably not a key player. If this bug is a cause of disease in dogs, I’d guess it’s something that’s been a cause of disease all along, but we just didn’t know about it, versus it being a new organism that’s emerged and is spreading in the dog population.

Do our “kennel cough” vaccines still work?

Yes (and no). We have good mucosal (i.e. intranasal, oral) vaccines for some respiratory pathogens in dogs that work quite well. The problem is that they don’t work against all causes of canine infectious respiratory disease. We have vaccines that will cover one or more of Bordetella, canine parainfluenza virus and adenovirus; while they don’t protect against other pathogens, protection against those three is important (especially the first two).

We also have a vaccine against canine H3N2 influenza virus. It’s been in short supply because of production issues over the past couple of years. Canine flu is a sporadic (but locally dramatic) cause of disease in dogs in the US. Like any flu vaccine, the canine flu vaccines are moderately effective and best for prevention of severe disease (versus prevention of infection), and are lower on my priority list for the average dog.

What do we do now?

  • Dog owners should relax. Think about your dog’s exposure risk and susceptibility to severe disease, and make some modifications to their routine if indicated. Talk to your veterinarian about respiratory disease vaccines. And did I mention relax?
  • As for me – Wait. Watch. Continue to collect as much data as we can. Continue to try to walk the fine line between increasing peoples’ awareness of CIRDC and avoiding paranoia/panic.

Why don’t we have a good canine disease surveillance system?

Money, specifically lack thereof. That’s not the whole issue but it’s a lot of it. The broader issues include:

  • Animal disease control and regulation has historically been developed for food animals. Animal health is usually under the purview of agriculture or food safety agencies. So, there is often little or no mandate to cover companion animals, and less expertise. There are often inadequate resources to cover core mandates with livestock species, let alone something peripheral like dogs. It’s not that these groups aren’t interested, it’s mainly that they don’t have the time, staffing or mandate to do much.
  • Limited veterinary infectious disease expertise. The veterinary infectious disease world is pretty small. There aren’t many of us and we have a finite degree of bandwidth.
  • Testing for CIRDC is scattered amongst various private, academic and government laboratories. Those system aren’t currently able to communicate effectively, and there are often various barriers to data sharing.  For effective surveillance, we need a coordinated, real-time system with integration of data across these sources. That’s probably a long way away.
  • There’s very little funding for companion animal infectious diseases, both for surveillance systems and targeted research. I think we get a lot of bang-for-buck with the limited money that flows to the area, but it’s really hard to get any money to investigate things like this. That means we don’t get the data we need and we don’t train more experts in the area.
  • Detailed study of disease situations like this requires collaboration with primary care veterinary clinics. That’s really tough because of the workload that they currently have – they’re swamped. Adding more work (usually unfunded) isn’t something for which most clinics are up, at least on a long-term basis. We can get little targeted studies done with some clinics, but it’s hard to do the broad work that’s needed with financial and IT support to make it viable over time.  

Am I optimistic or pessimistic for where we’ll be with CIRDC heading into 2024?

I’m fairly optimistic. I’ve felt this situation was overblown from the start, with some real disease issues over-amplified by media and social media. I’m not dismissing the real impacts in some areas and on some dogs, but I’ve never been convinced that we have a massive, broad outbreak. There have been real impacts, real concerns, as well as excessive fear, and there’s been a lot of good work done trying to sort this out. Increasing awareness about CIRDC in dogs and disease prevention is always good. As we head into 2024, hopefully we’ll see a continued die-down in reports of (and actual) disease, and improvements in infection prevention.

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The World Organization for Animal Health Health (WOAH, formerly the OIE) has issues a call to countries to live up to their commitments to phase out the use of antimicrobials for growth promotion in animals. This is low-hanging fruit in terms of antimicrobial stewardship that you’d think would have been addressed by now, but is still an issue in some countries (but was phased out in the US in 2017 and in Canada in 2018).

Let’s review some of the language and terminology around how antimicrobials are used:

In animals, antimicrobials can used to treat existing clinical infections (therapy), to prevent infections in high-risk situations (prophylaxis), and to treat animals that are at high risk of already being infected but are not yet sick (metaphylaxis). Those are all considered veterinary uses for antimicrobials, and they’re all justifiable under the right circumstances (though there are still concerns about overuse, particularly with metaphylaxis and prophylaxis).

Unfortunately, antimicrobials are also still used in some places to promote growth of food-producing animals. That kind of use has nothing to do with prevention or treatment of disease. Instead antimicrobials are used in these cases to alter the intestinal microbial populations of the animals, which can result in better growth rates. From a production standpoint, that can be good, but it increases the risk of antimicrobial resistance developing, which can impact animals, humans and the environment.

Another key term is “medically important” antimicrobials, which are those that are the same drug or in the same drug class as antimicrobials used in humans.  If resistance to these drugs develops through their use in animals, that could pose risks to humans. So we definitely do not want medically important antimicrobials used simply for promoting animal growth; they need to be reserved for when they’re really needed (in either animals or people).

The World Health Organization (WHO) categorizes all antimicrobials as either medically important or not medically important, and classifies the medically important antimicrobials into different priority levels (a revision of this classification will be released soon). Pretty much all of the antimicrobials that are used for treatment, prevention or metaphylaxis in animals are medically important, and some of these are also used for growth promotion. There are also various not-medically important drugs that are used for growth promotion. Resistance concerns regarding the use of the latter are low, but not zero, as there’s still potentially an environmental impact (pretty much completely unknown at this point), and we can rarely say there’s absolutely no risk of cross-resistance or co-selection of resistance to an unrelated medically important drug.

In 2016, WOAH member states agreed to stop the use of “highest priority critically important antimicrobials” (HPCIAs) for growth promotion in animals and phase out the use of all antimicrobials for growth promotion “in the absence of a risk analysis.

What’s happened since then? Not enough:

  • 20% of member countries still report the use of antimicrobials for growth promotion in livestock.
  • It’s estimated that 76% of those countries have not done a risk analysis to try to identify risks and justify their antimicrobial use.
  • At least 50% of these countries have no regulatory framework to regulate use of antimicrobials for growth promotion.
  • In some countries, antimicrobial-containing feeds are not labelled, so farmers and veterinarians may not always know that they are feeding antimicrobials to their livestock (which raises a variety of issues)
  • 11% of member countries reported still using HPCIAs for growth promotion in livestock. This includes the use of colistin, an ol antimicrobial that’s become a drug of last resort for some life-threatening, highly drug-resistant infections in people. That’s a big concern.

Phasing out antimicrobials for growth promotion should be a no-brainer, particularly phasing out such use of medically important antimicrobials. WOAH’s new statement is pretty clear:

WOAH calls on its Members to restrict the use of antimicrobials solely to veterinary medical use and to actively engage in dialogue with the concerned parties to achieve a total ban on the use of antimicrobials as growth promoters, starting with those that are critically important for human health.”

Is improving animal production important? Yes, particularly in developing countries. Yet, there are better and more sustainable ways to do that than feeding animals antimicrobials for no other reason than improving their growth.

The US Food and Drug Administration (FDA)’s 2022 Summary Report on Antimicrobials Sold or Distributed for Use in Food Producing Animals has been released. It includes some good signs and some bad signs in terms of curbing antimicrobial use (AMU) in the US, but it’s clear we still have a lot of room to improve.

Here are a few highlights from the report (all referring to the US, of course):

  • Antimicrobial use in food animals, based solely on sales and distribution, decreased on a mass (kg) basis by 36% since 2015 (which was the last peak in this measure of AMU).
  • Antimicrobial use increased 4% from 2021-2022.

Comparing to the 2015 historical high and saying “we’re doing a great job” isn’t really a good approach. It’s useful for context, but the year-to-year increase from 2021-2022 is more of a concern, as we really should be aiming for substantial year-to-year decreases in AMU.

For any 2020-2023 data, we always need to ask the question “what was the effect of COVID-19?” We really don’t know in this case, but there could have been impacts on sales and use because of changes in animal management and access to veterinary services. So, I wouldn’t read too much into the 2021 blip; it’s not a great sign, but it’s possibly something we’ll see corrected given some time. We’ll see.

  • The increases antimicrobial sales in 2022 were largely driven by increased sale of tetracyclines, the most common drug class used in livestock, and the one that is probably most ripe for reduction because of its frequent use for prophylaxis.
  • Sales of penicillins decreased by 1%, while sales of aminoglycosides increased by 10%, macrolides increased by 8%, and lincosamides increased by 11% (see figure below).

This raises some concern. From an antimicrobial stewardship standpoint, we’d like to see decreases in sales and use of higher-tier drugs. Here, we’re seeing the opposite: a decrease in sales of lower-tier penicillins with increases in sales of some higher-tier drug classes.

  • The swine industry was the leading consumer, accounting for 43% of total antimicrobial sales for use in animals, closely followed by cattle at 41%.
  • The poultry industry continues to use relatively limited amounts of antimicrobials, with chickens accounting for 2% and turkeys for 12% of sales.

This is unsurprising, and also highlights where we can have the biggest impacts in terms of reducing AMU. It also shows how poultry farmers have lead the way by reducing AMU aggressively and voluntarily.

The graph below shows the different antimicrobial classes used in each species, which is an important consideration. It highlights the dominance of tetracyclines, particularly in swine and cattle. While massive amounts of antimicrobials are used in animals, most of the use is lower-tier drugs like tetracyclines. These drugs are still important in people, but are not as critical as other drug classes as tetracyclines are not typically key treatments for serious disease in humans. The WHO has a prioritization process to categorize different antimicrobial drug classes to help with assessments like this (and an updated version is due to be released imminently).

At the same time, we need to remember that mass isn’t everything, especially when it comes to AMU. In many ways, I’m less concerned about that big fraction of tetracyclines than I am the small fractions of cephalosporins and fluoroquinolones. The latter are important drug classes in humans, and we know that use in animals can contribute to antimicrobial resistance (AMR) in human pathogens. So that small degree of use in animals might have a disproportionate impact on AMR overall. It’s one of the reasons that crude mass-based metrics like this aren’t good a good way to set targets for AMU, but they get used because they’re the easiest to measure.

  • All medically important antimicrobial were used for “therapeutic indications,” as a result of the ban of use of antimicrobials for growth promotion in 2017 (see figure below).

That’s good. Non-veterinary/non-therapeutic use of medically important antimicrobials isn’t needed, so it’s low hanging fruit when it comes to reducing AMU. However, we have to acknowledge that “therapeutic use” is a designation, not necessarily what was actually done, as there’s still massive overuse of antimicrobials in animals in situations where there’s no evidence that there would be a therapeutic effect (including prophylaxis).

Ultimately the FDA report provides some mixed signals overall. We’ll need to see how things develop over the next few years to determine if there was a COVID-19 effect on these data. Regardless, it’s abundantly clear that we still have a lot of room to improve, and we need to act now.

Zero antimicrobial use in animals isn’t a realistic goal. We need to use antimicrobials for animal health and welfare purposes, but we need to use them better.

I’d guess that a substantial amount of antimicrobials that are purchased for use in animals are actually used to “treat” people: they make the user feel better for doing something, while doing little or nothing to actually make the animal feel better in many cases. We have lots of situations where antimicrobials are needed in animals, but we still have massive overuse that needs to be eliminated.