The UK’s FIP Advice Team has released new antiviral drug treatment guidelines for feline infectious peritonitis (FIP).

A major change is introduction of twice daily dosing of oral GS-441524, based on the observation that inter-cat variations in drug absorption and metabolism might account for some of the treatment failures that are seen with once daily dosing.

There’s also more emphasis on using oral GS-441524 as the sole treatment, without an initial injectable course of remdesivir. Combination therapy (starting with injectable remdesivir and then transitioning to oral GS-441524) should be reserved for cases where the cat is critically ill and there’s reasonable concern that the cat will not absorb oral medications well.

The new information for veterinarians and pet owners will be online soon, and I’ll post an update here when it’s available (currently I just have is the pdfs, but this platform isn’t as good for sharing those).

And finally a little reminder from the Canadian perspective:

  • Canadian veterinarians who have access to our Dropbox with the guidance for the Emergency Drug Release (EDR) process to access remdesivir and GS-441524: the treatment guidance document in the folder has been updated accordingly.
  • Canadian veterinarians looking for access to these guidance documents: email me or contact me through the Worms & Germs Blog contact link at the top of the page.
  • Canadian cat owners: these drugs for treating FIP can only be legally imported by veterinarians. If you have a cat with FIP, discuss the treatment options with your veterinarian, but there is no longer any need to resort to questionable black market drugs for your cat.

Now that Canadian veterinarians can legally import antiviral drugs for treatment of feline infectious peritonitis (FIP), there’s no (good) reason for people in Canada to be sourcing these drugs on the black market. However, there are still many countries (e.g. the US) where it’s still tough or impossible to get these drugs legally, so the black market for them will likely continue to thrive. That’s a problem for many reasons, one of which is the highly questionable quality of black market drugs, and a recently published study (Kent et al. J Am Vet Med Assoc 2024) highlights that particular concern.

The researchers collected leftover drugs from people who had purchased FIP antiviral drugs on the black market to treat their cats. They ended up with 127 drug samples. The results were not surprising, but not good.

Black market injectable remdesivir and GS-441524:

  • 95% of samples contained more drug than the label stated – on average 39% more.
  • Only 2/87 products were within 95-105% of the stated concentration, the range that is required for licensed drugs produced under Good Manufacturing Practices (GMPs).
  • The average pH of the drugs was 1.3 – that’s really acidic. The acidity is needed to keep the drug in solution, but it shows why injection site problems are so common.

Black market oral GS-441524:

  • These samples were all over the board. Fourty-three percent (43%) contained more drug than stated on the label (on average 75% more), and 58% contained less durg that stated on the label (on average 39% less). One product contained only 18% of the amount of drug that was stated on the label.
  • Only 3/40 samples were within the 95-105% range of the stated concentration.

One injectable and two oral products that were supposed to be GS-441524 were actually remdesivir.

Even interpreting the labels on these samples was a challenge. As black market products, there’s no requirement for any standard (or accurate) labeling. The paper mentions that “It is known within the FIP treatment community that producers report the strength of the pills based on what is thought to be bioavailable to the cat. Therefore, the strength of the pill expressed on the label reflects the producer’s estimation of the equivalent SC dose. This is presumably done to make the process of switching between injectable and oral formulations easier for lay owners.”

  • Some labels stated the amount of drug that was (supposed to be) there, while some basically said “we put in X amount but expect only part of it to absorbed by the cat, so we’ll estimate that it actually means Y amount” …presumably with no real data to back up their estimate.

So, it’s possible the products contained more drug that they indicated based on the assumption of lower bioavailability (less drug making it into the cat’s system after it’s given orally). However, that doesn’t account for the more than 50% of samples containing less drug than stated on the label. The fact that the authors had to make various guesses makes some of the percentage calculations debatable (that’s not a criticism, there’s really no good way to do it), and highlights challenges for cat owners who order the drug and treat their cats themselves. If these researchers struggled to guess how much drug should have been there, what can the average cat owner discern?

They also tested a product that said it was something else, but which is known to actually be GS-441524 (Xraphconn). The labels said the tablets were 50 or 100 mg of “MT-0901,” but they were, as expected, GS-441524, with 18 or 47 mg per tablet, respectively. This highlights yet another black market “buyer beware” issue.

A quote from the paper highlights even more concerns with these drugs: “Due to the unlicensed nature of this industry, packages misrepresenting the contents and intended use of these GS-441524 products are common. Products are shipped in boxes labeled as facial masks, serums, or cat nutrients, possibly to curb suspicion during shipment.  Additionally, some products are marketed vaguely as FIP cures with active ingredients other than GS-441524. For example, the brand OM markets their products as containing 50 mg of sea sponge extract, and Mutian products are advertised to also contain vitamin B12. Mutian lists its active ingredient as MT-0901 and is described by the company as an adenosine nucleside analogue. While the LC-MS/MS technique used here was unable to determine whether sea sponge extract, B12, or any other adenosine nucleoside analogues were present in the samples, all 127 samples did contain GS-441524.

So what do we need?

In countries where effective FIP drugs are legally available, we need to use those drugs.

  • Approved products manufactured by reputable companies are made with strict quality control and testing practices, which gives us confidence that the products contain the drug that is supposed to be there at very close to the stated concentration.
  • Black market drugs and drugs compounded from non-pharmaceutical grade compounds do not provide the same level of assurance, so there is more risk.
  • In Canada, there’s absolutely no reason anymore to use black market drugs or otherwise formulated drugs not from a reputable company with robust quality control practices.

In countries where effective FIP drugs aren’t legally available, legal access needs to be facilitated.

  • These drugs save cats’ lives, and there’s no downside to allowing legal importation. It’s otherwise occurring illegally, and it’s far better for cats, owners and veterinarians to have access them under a controlled process where product quality can be assured.

Candida auris is an emerging infectious disease threat. This fungus causes disease almost exclusively in immunocompromised people, with infections most often acquired in hospital. While infections are rare, it’s a bit problem because mortality rates tend to be very high (20-60%), it can cause outbreaks in healthcare facilities, it can live on the skin of healthy people, antifungal resistance is common and routine disinfectants don’t always work very well.

That’s a perfect combination for a nasty hospital-associated infection, and when something is a problem in hospitals, we have to consider whether that will spill into the community. Since infections are most often in highly compromised patients the community risk is probably low, but since it’s an emerging disease, we need to pay attention.

Below is a map of human Candida auris cases in 2022 from the US Centers for Disease Control (CDC).

As I often say, when we see a new disease threat in people, we need to look at the risk to (and from) animals as well. Not to blame them, and not to freak people out, but to understand the risks. More often than not, the animal side of the equation is completely ignored, or there’s overreach and unnecessary blame on an animal source. A logical middle ground is needed, whereby we look and try to understand, addressing any potential problems proactively, and without panic or sensationalism.

What do we know about C. auris in animals?

Very little so far. A study of 87 dogs in India (Yadav et al. 2023) reported detection of C. auris in the ear of 3 dogs and the skin of 1 dog. It’s a bit hard to follow the results of that paper, and not all the infections are well described, but at least one of those dogs had chronic skin and ear infections, and had been previously treated with antibiotics and antifungals. Candida auris was identified on two samples from that dog taken a month apart; that’s important information as we need to understand whether animals can be long-term carriers, short-term carriers or are largely resistant to infection (in which case a positive test result is simply the result of transient contamination, not carriage or infection).

Another study of 251 shelter dogs in Kansas (White et al. 2024) found C. auris in an oral swab from 1 dog, a two-year-old Labrador cross that had recently been surrendered. When they looked at the genetic makeup of the C. auris, it was the same clade (group) as C. auris isolates that have been found in people in a couple of places in the US, including Chicago.

  • The isolate was resistant to fluconazole, amphotericin B and terbinafine, but susceptible to voriconazole, itraconazole and caspofungin. So, it was resistant to some common antifungals but not others, but that degree of resistance is still a concern, since our antifungal treatment options are even more limited than our antibacterial treatment options.
  • It’s hard to say where the dog got infected. It could have been acquired in the shelter or before the dog was surrendered. No one at its previous home was immunocompromised, and the dog didn’t visit human hospitals (those are the first two risk factors for which I’d look). No shelter workers were known to have been infected, but the staff weren’t tested. The dog hadn’t traveled, had no previous medical issues and had not been treated with antifungals. No other dogs in the shelter tested positive for C. auris, including the littermate with which the affected dog was surrendered. The dog was subsequently adopted, and 2 years later,neither she nor the other dog in her new household were positive for C. auris. (Why was the dog only re-tested 2 years later? Probably because the C. auris was a secondary finding from the original study, and it took that time for the side-work to be done, plus the confirmatory testing).

When we’re thinking about emerging diseases like C. auris in animals, there are two main aspects to consider:

  1. Can animals be a source of infection for people? i.e. is the disease zoonotic?
  2. Can the pathogen cause disease in animals? Sometimes this animal health component is overlooked.

Actually, we should probably add one additional consideration: can animals be infected by people?  While it’s usually overlooked, we have ample precedent of infectious diseases emerging in human healthcare and spilling over into animals, particularly companion animals (e.g. methicillin-resistant Staphylococcus aureus (MRSA) and various other multidrug-resistant bacteria).

While it’s rare, it’s clear that dogs can be infected with C. auris, at least temporarily. It’s fair to expect that that applies to other species too.

So, that leads to the big question… can animals infected with C. auris infect people?

  • Who knows, but probably.

It’s logical to assume that an infected dog could infect a susceptible person, just like an infected person could infect another susceptible person. Fortunately, this organism tends to infect highly immunocompromised people, and most dogs don’t have much contact with those individuals. The risk would be greatest from a dog that had direct contact with an infected person and then contact with another high-risk person (or a dog that lived with an infected person who was successfully treated, but could then potentially be a source of re-infection for that same high-risk person).

What is the risk of C. auris to and from hospital visitation dogs?

Hospital visitation dogs are a unique group with which I’ve worked on and off. We know that these dogs are at increased risk of picking up a variety of infectious agents during hospital visits (e.g. high rates of (albeit transient) MRSA acquisition). A similar situation could potentially occur with C. auris. Fortunately, the risk of exposure of dogs is going to be much lower than with many other hospital-associated pathogens, since C. auris is still very rare even in people. However, this should be yet another reminder of the need to follow appropriate guidelines for canine hospital visitation programs, and to take efforts to reduce the risk of exposure of dogs during such visits.

When MRSA first emerged in dogs, we tended to see it most in pets of healthcare workers and dogs that visited hospitals. Visitation dogs are at the forefront of exposure to a variety of things that are concentrated in human healthcare facilities. If we’re going to see an animal spreading C. auris to people, this is a prime way for that to occur.

We need to think about potential human-animal and animal-human aspects of C. auris, and use basic infection prevention and control measures to reduce the risk of transmission, in either direction. We shouldn’t over react since we have no evidence of a problem, but we also shouldn’t wait for definitive proof before taking reasonable precautions.


A fatal Alaskapox virus infection in a person in (unsurprisingly) Alaska has once again focused a lot of attention on this rather obscure virus. When I last wrote about Alaskapox virus in 2020, we had a lot of unanswered questions about it, yet today we’re not that much further along, largely because this virus is still really rare. Rare viruses are hard to study since there aren’t many natural infections from which to learn, and they usually don’t attract much funding to allow for in-depth research. That’s particularly true when infections don’t seem to have very serious consequences, as was the case until this latest infection.

Alaskapox virus is a member of the Orthopoxvirus genus, which includes poxviruses such as smallpox, mpox (previously known as monkeypox) and cowpox. Some poxviruses are very host-specific, meaning they only infect one species. For example, smallpox only infected people, but others are more promiscuous, circulating in a reservoir species but also able to spill over into other species, as with mpox.

Based on the genetic makeup of Alaskapox virus, part of its genome seems to come from the ectromelia virus, a mouse poxvirus, suggesting the two viruses are somewhat related. Given what we know about the reservoirs of many poxviruses (which are often rodents), the genetic makeup of Alaskapox virus, and the rarity of human disease (which supports human infections being spillovers from a separate reservoir species), rodents have been assumed to be the natural reservoir. It’s been stated that the virus has been found in a variety of rodent species, including red-backed voles, shrews and red squirrels, although I can’t find actual research papers describing that.

Alaskapox was first identified in 2015, and there have been 7 confirmed human infections to date. Until now, they were all mild and got better on their own. The most recent case has gotten attention both because this is a rare disease, but more importantly because the patient died. That understandably amplifies concerns about the virus, but it’s important to keep things in perspective: There’s no indication that this virus or anything related to it has changed. It seems this is simply another rare spillover infection, but it unfortunately occurred in a person with a compromised immune system, and therefore had much more dire consequences.

The affected individual was undergoing cancer treatment, putting him at much greater risk of acquiring infections and developing serious illness from things that would normally make a person significantly sick. The patient first developed signs of Alaskapox in September, starting with a tender lesion around his armpit. It gradually got worse, probably because his cancer treatment impact his body’s ability to eliminate what would normally be a pretty mild infection. He continued to deteriorate and died in January, with a variety of problems including kidney and respiratory failure.

How the person got infected has generated a lot of discussion, and some overreach. Since this is a rodent-associated virus, direct contact with rodents would be a likely source. If there’s no known direct contact with rodents, then we have to think about environmental exposure (e.g. contact with rodent feces) or, more likely, contact through an infected intermediary. Cats jump to the top of that list, as they can have a lot of contact with rodents and people. Cats are susceptible to some rodent poxviruses, like cowpox, so the concern is that a cat could have caught an infected rodent, become infected (with signs of disease or not), and then passed the virus on to a person.

It’s a logical thought process, but it’s just a thought process at this point.

Two common factors are present in human Alaskapox infections: the people lived in wooded areas, and they had contact with dogs or cats that could have encountered wildlife. Those are important things to note, but they also probably apply to a pretty large percentage of the population in Alaska. In this case, the infected person lived in a wooded area and cared for a stray cat that hunted small mammals. He had direct contact with the cat, as it would sometimes come in his house and often scratched him. (That’s a whole other issue… cat scratches create risk for various infections, especially in a high-risk person like a cancer patient. There needs to be better awareness of that and discussion of the importance of first aid after cat scratches). Officials in Alaska have taken a reasonable line, saying the cat was a possible source, but not more than that.

We need to understand the role of cats in Alaskapox virus transmission, just like we need to understand the role of animals in various other emerging diseases. Too often, it’s one extreme or the other: either the role of animals is ignored, or people jump to conclusions (e.g. virus infects mice > cats catch mice > cats hang out with people > ergo the human infection is the cat’s fault). We need to consider the role of animals and take reasonable precautions to avoid potential disease transmission, but at the same time, we need to actually investigate those potential routes of transmission, and not stop at “this seems to make sense.”

As I mentioned, rare viruses are hard to study, and it’s really hard to get funding for any infectious disease work with companion animals, but a good start would be testing cats for the presence of antibodies against Alaskapox virus, focusing on cats that have access to rodents. That would give us an idea of how commonly cats get infected, and a starting point for understanding their role (or not) as a bridging host for this virus. For this case, since the potential source cat is known, it would be very useful if it could be caught and tested. If the cat has antibodies against the virus, it provides more support that the cat was the source, but we’d still want to know more about how common exposure to Alaskapox is in the general cat population to put things into better context.

How much time, effort and money to put into a rare disease is always a controversial topic. Some people want to be proactive. Some want a clear business case, which is tougher to make for a rare disease. However, a little effort into more rodent surveillance, testing of cats to see how much spillover occurs into this species, and testing people for antibodies to see how many infections might be occurring under the radar would be a relatively inexpensive but informative start.

Hot off the press (at long last), here is the latest version of the World Health Organization’s Medically Important Antimicrobial List.

What is the WHO Medically Important Antimicrobial List?

It’s a document that categorizes all the classes of antimicrobials that are used in people and/or animals by how important they are to human medicine, and assesses the human health risks associated with use of these drugs in animals.

How’s is the list made?

The process is driven by an expert panel that includes people with a wide range of expertise from across the world. I was Chair of this revision, and it was a great group. Discussions weren’t always easy (which is often a good sign), but they were productive.

Please note that the comments below are my personal opinions, not necessarily those of the working group.

What is this list meant to achieve?

The document’s subtitle is “A risk management tool for mitigating antimicrobial resistance due to non-human use.” That’s a bit overstated, as we didn’t assess risks of antimicrobial use in plants or crops (but hopefully that will be rolled into future revisions), but it does highlight the overall goal: to assess the risks posed by antimicrobial use in animals, and use this as the basis for thinking about how we use and monitor antimicrobial use in animals.

The assessment is based on a few things, including the human diseases different drugs are used to treat, and any evidence of use in animals leading to increased antimicrobial resistance in human infections.

A brief description of the process for creating the list:

Step 1 was sorting out which drug classes are used in humans only, animals only, or both (something that takes a surprising amount of work and digging).

Step 2 was assessing each drug class through the appropriate pathway in the figure below:

The criteria for each of the boxes in the diagram are explained below:

C1: The antimicrobial class is the sole, or one of limited available therapies, to treat serious bacterial infections in people.

 C2: The antimicrobial class is used to treat infections caused by bacteria 1) possibly transmitted from non-human sources, or 2) with resistance genes from non-human sources.

Prioritization factor 1 (PF1): The class contains at least one antimicrobial that is BOTH on the WHO Essential Medicines List  and is classified as Watch or Reserve list of the AWaRe classification of antibiotics.

Prioritization factor 2 (PF2): The antimicrobial class is used to treat infections in people for which there is already extensive evidence of transmission of resistant bacteria (e.g., non-typhoidal Salmonella spp.) or resistance genes (e.g., E. coli, Klebsiella spp., S. aureus and Enterococcus spp.) for the particular antimicrobial class from non-human sources, and these infections are frequent causes of invasive and life-threatening infections in people.

Ultimately, each antimicrobial class ends up in one of six categories:

Medically important (in descending level of importance)

  • Authorized for use in humans only
  • Highest priority critically important antimicrobials (HPCIA)
  • Critically important antimicrobials (CIA)
  • Highly important antimicrobials (HIA)
  • Important antimicrobials (IA)

Not medically important

  • Drugs that are authorized for use in animals only and which have no evidence of cross-resistance or co-selection of resistance with medically important antimicrobials.

There’s a section in the document that outlines the changes from the previous version of the list. I’ve listed the changes here:

  • Addition of new categories for human only and animal only antimicrobials (details above).
  • Changes to PF1 and PF2 (details below).
  • Downgrading macrolides from HPCIA to CIA.
  • Downgrading aminopenicillins from CIA to HIA.
  • Upgrading phosphonic acid derivatives (fosfomycin) to HPCIA.
  • Upgrading nitroimidazoles from IA to HIA.
  • Separation of ketolides from macrolides, and separation of fidaxomicin from other macrolides, since they’re so different.
  • Separation of eravacycline and omadacycline from the tetracycline class, since there are major differences in resistance mechanisms and concerns with these drugs.
  • Separation of plazomycin from aminoglycosides for similar reasons.

A few questions commonly come up about the revision:

Why create the human use only category?

This was required to ensure that important, new human drugs are appropriately categorized. Part of the prioritization process is looking at the evidence that use in animals contributes to resistance in people (PF2). If we have new drugs that are not used in animals, there’s no way new drugs could hit that bar. So, a precautionary approach is needed.

  • If the drug class is not licensed in animals, it gets in its own category, with the implication that it’s importance is at or above that of the HPCIA group. If we didn’t do that, important drug classes like carbapenems (that are used in critically ill humans) wouldn’t be able to hit the bar to be “highest priority” unless we started using them a lot in animals and found a resistance link… at which point we’re already too late. We need to be proactive and protect these important drugs, so they got a new category.

Why create the animal use only category?

In the past, there was an Annex to the list that listed animal-only drug classes, but they didn’t undergo a formal review and the list was incomplete. While drug classes not used in humans are reasonably considered not to be medically important, bacteria don’t read guideline documents, so it’s still important to properly assess these drugs. The new process built in an assessment of the animal-only antimicrobials to see if there was any real or plausible evidence that their use could co-select for resistance to medically important drugs (e.g. could resistance to the animal only drug also confer resistance to a drug used in people).

Why change the prioritization factors?

There were two prioritization factors in the previous version, but there was a lot of overlap between them and a lot of confusion about what they meant. There was also a need for a bit more specificity.

  • PF1 was changed to incorporate the newer WHO AWaRe document, that categorizes antimicrobials in humans into Access, Watch and Reserve. Since there was a rigourous process used to determine how important a drug is for humans for that list, it made sense to build that into this assessment too.
  • PF2 was tinkered to add in consideration of the severity of human disease. Resistance to any bacterium that causes disease in people is a concern, but the concern is greatest for diseases that are common and severe.

Why downgrade some drugs, even when they’re used a lot in people?

Downgrading the category of certain drug class doesn’t mean “go ahead and use it at will.” It means they are less of a concern than drugs in the higher categories. We have concerns about all medically important drugs, but we can’t just put them all in the same high category. If we did that, there’d be no guidance and we’d be saying “we don’t care if you use a new fluoroquinolone versus an old penicillin” – but we most certainly do care about a decision like that. There needs to be separation of categories for this document to be useful in risk assessment, surveillance and guideline development.

  • For example, macrolides were controversial as HPCIAs in the last version of the list. On one hand, they hit the criteria to be an HPCIA at the time. On the other, I’d much rather use a macrolide in an animal than HPCIA drugs like 3rd generation cephalosporins and fluoroquinolones. By having them all as HPCIAs, it basically says the risk of use is comparable and it doesn’t matter which one we use. I think most people in antimicrobial stewardship circles would agree that we’re much less concerned about macrolide use and resistance compared to those other classes.
  • The downgrading came as a result on the new PF2, which incorporates severity of disease into the evaluation. While macrolides are important for treating campylobacteriosis in people (the main driver for the “yes” for PF2 previously), most cases of this disease are self-limiting, antimicrobial therapy is not usually required, and Campylobacter spp. are infrequent causes of invasive, life-threatening human disease.

A document like this isn’t meant to be the final word on how we use antimicrobials in animals, but it’s an important part of the equation. We need to consider this list along with other things like the WHO Essential Medicines List, various treatment guidelines, and drug accessibility. This list is a foundational document for considering how we use and monitor antimicrobial use in animals.  


Great news for Canadian veterinarians, cat owners and cats: We now have legal access to drugs that can treat feline infectious peritonitis (FIP), a disease that’s historically been considered almost invariably fatal in cats, prior to the discovery of these very treatments.

I’ll keep this short (-ish… since Moe keeps complaining about my long posts).

We’ve known for a few years that the antiviral drugs remdesivir and its close relative GS-441524 (and to a lesser degree molnupiravir) can be highly effective for treating FIP, with really high cure rates, although the drugs are extremely expensive.

But the biggest problem has been drug access. None of these drugs are licensed for animals in Canada.

The two drugs licensed for use in humans (remsidivir and molnupiravir) technically could be imported for veterinary use based on an Emergency Drug Release (EDR) if purchased directly from a manufacturer, but the manufacturers would not agree to this. So for the past few years, people have been purchasing and illegally importing black market drugs and using them to treat their cats themselves, because without these drugs most cats with FIP will die. Sometimes owners were lucky to have some veterinary support, sometimes they did not. Veterinarians can’t recommend or give an illegal product to a patient, but in some cases could at least provide some supportive care through the process. It’s a really tough situation for everyone involved.

Legally compounded remdesivir and GS-441524 have been available in Australia, the UK and South Africa, but we were not able to access those products either – until now. Working with Health Canada’s Veterinary Drugs Directorate (VDD), we’ve been able to get their approval to import legally compounded versions of both these drugs from the UK. Veterinarians have to request permission to import the drug via an EDR every time they want to use it (i.e. they can’t import a supply to keep in the clinic for when they need it, it needs to be requested for each patient), so there are still some logistical hoops to jump through, but ultimately they’re not a big deal. The drugs still aren’t cheap either, but probably cheaper than what I’m hearing most people are paying for the illegal versions (that also have no assurance of quality control or safety).

To veterinarians:

  • We’ve developed guidance documents about treatment regimens and the EDR process to help make these treatments more widely accessible. Contact me directly or through the blog’s contact link (in the menu bar at the top of the page) to get access to those. We’ll try to keep everyone up-to-date on changes to treatment regimen recommendations as we go, as this is a fairly new and therefore dynamic field.

To cat owners:

  1. These drugs need to be imported by a veterinarian who has a veterinarian-client-patient relationship (VCPR), meaning the veterinarian who is your cat’s healthcare provider. They cannot be imported by cat owners, and they cannot be imported by veterinarians for sale to non-clients, or for use on cats that are not their patients.
  2. We will be working with veterinarians to help them treat cats with FIP, but we cannot work directly with cat owners. If you have a cat that might have FIP, you need to work with your local veterinarian, or ask for a referral to a veterinarian who can offer the treatment.
  3. If you’re in the US, Canadian veterinarians cannot import this drug to ship to the US. It is for cats being treated by Canadian veterinarians. As far as I know, there is still no ability to import these products into the US (hopefully that will change soon too).

This is a great example of what needs to be done to tackle infectious diseases, especially in minor species (particularly non-food animals) and smaller markets (like Canada) where lack of access to important treatments, vaccines or other products in general is a much broader issue, but one that’s been flagged repeatedly as an important area to address. This is a small but important example of what can be done when companies, veterinarians and regulators work together to find solutions.

When we talk about vaccines of dogs*, we tend to split them into “core” and “non-core” vaccines.

(*The same applies to cats. I use dogs by default for posts like this, which sometimes gets me an earful, but I’m not actually ignoring cats.)

Core vaccines are those that every animal should get (e.g. rabies vaccine in areas where rabies exists, canine parvovirus in areas where dogs exist). Non-core vaccines are those that aren’t required by every dog, or that are less convincingly needed in every case.

Non-core vaccines are also often referred to as “lifestyle vaccines,” because the nature of the dog’s (or cat’s) lifestyle can put the animal at more or less risk of exposure to a disease, which affects the relative need for vaccination. Respiratory diseases are a great example. All dogs are at some degree of risk, but the risk is much higher in dogs whose lifestyles create more dog-dog contact (e.g. going to daycare, boarding, off-leash dog parks). That’s a good way to think about how to prioritize vaccination for an individual dog, but it misses a big part of the disease prevention equation.

When I’m assessing the need for vaccination in a pet, I think about two main things:

  1. Risk of exposure. The lifestyle aspect covers this.
  2. Risk of serious disease. This often gets ignored.

Some dogs are at higher risk of severe disease or death from respiratory infections. I’d put senior dogs, brachycephalics (i.e. flat-faced breeds), pregnant dogs, dogs with pre-existing heart or lung disease and dogs with compromised immune systems on that list. I’m more motivated to protect them because the implications of infection are higher, even if their risk of exposure may be fairly low.

Take my two dogs as an example (again):

Ozzie is 1.5 years old and healthy. If he gets a respiratory infection, most likely he’ll have transient disease and, while it will be annoying (for him and us) and I’d like to prevent it, odds are quite low he’ll suffer any serious consequences.

In contrast, Merlin is an 11 year old dog with chronic lymphoid leukemia who’s been getting chemotherapy for about 2 years. He’s doing really well, but he has a significant chronic disease and he’s old. If he gets a respiratory infection he’s at much greater risk of dying than Ozzie.

If we look at lifestyle of these two dogs, they’re similar, since they do everything together. The exception is in the summer when we go to a cottage for 2 weeks. Since 2 weeks with Ozzie at a cottage isn’t much of a vacation for us or Merlin, he went to a local day care for part of the time. (An exhausted Ozzie is a good Ozzie, and he often came home close to comatose, which was perfect.) So Ozzie has a major additional lifestyle risk factor, therefore he’ll get a respiratory vaccine again this summer (both because of the risk and because the day care requires it).

Merlin doesn’t have that same direct exposure risk, but he has some added risk through being exposed to Ozzie. Should he get a respiratory vaccine? If we just look at his lifestyle, we’d say no, he’s pretty low risk for exposure. However, his higher risk for severe disease increases my motivation to vaccinate him, and he’ll likely get a respiratory vaccine this summer at the same time Ozzie does.

Lifestyle is definitely important to consider, but we need to make sure we don’t just focus on the dog’s lifestyle and consider the dog (or cat) as a whole.

I debated writing about this now since it’s an ongoing situation with a very unclear outcome, but that’s medicine. We also don’t have a lot of camelid content on the blog, and there’s an infectious disease component to this case, so figured it was worthwhile.

Mickey (photo right) is an older male alpaca, part of my small group.

Why do I have alpacas? Here’s the short version:

  • I had a flock of rare breed sheep.
  • Coyotes starting picking off the sheep so I got a llama (Dolly) for predator control.
  • Dolly sucked at her job, so I was soon left with no sheep and a llama.
  • I then got some alpacas to keep the llama company.

This past Saturday, we found Mickey down on his side and couldn’t get up. I had thought that he looked a little weak in the hind legs earlier that week and this was presumably a progression of that problem. He was bright, alert and a pretty textbook spinal disease case. Specifically, his signs were consistent with a spinal lesion between the 3rd thoracic and 3rd lumbar vertebrae (T3-L3), given the severity of his hind limb abnormalities but pretty normal front limbs.

The two leading causes for this condition in an alpaca are:

  1. Parasite migration through the spinal cord due to infection with the deer meningeal worm Parelaphostrongylus tenuis (P. tenuis).
  2. Spinal trauma. Mickey and the boys chase each other around at times and it’s been icy. I didn’t appreciate anything in his back that would suggest a spinal fracture or other traumatic event, but sometimes it can be hard to tell.

While I couldn’t rule out trauma, parasitic migration made more sense, and P. tenuis is a major issue for camelids (like alpacas, llamas) and moose in some regions. Like many parasites, it has an unusual life cycle (see illustration below):

  • P. tenuis normally lives in white tailed deer, which are abundant around here. The adult parasites live in the subdural space and associated tissues in the central nervous system. Females lay eggs in blood vessels, and the eggs travel through the blood to the lungs where they develop into larvae (L1 stage). The larvae penetrate the small air sacs (alveoli) in the lungs and are coughed up and swallowed. They’re then passed in the feces, and subsequently infect slugs and snails, developing to their L3 larval stage.
  • If an animal ingests infected slugs or snails, the larvae move from the intestinal tract and somehow find their way to the central nervous system. In white tailed deer (the definitive host), they develop in gray matter of the spinal cord and then migrate to the subdural space, mature to adults and the life cycle starts again, usually without causing any problems for the deer. However, in other species like alpacas, the larvae don’t mature, and instead stay in the gray matter, causing inflammation and significant damage. Usually this damage predominantly affects control of the hind limbs, but depending on the location(s) to which the parasites migrate, damage to other parts of the spinal cord or brain can occur, so it’s on my list for any neurological disease in a camelid.

Back to Mickey. Given the odds of parasitic disease, the lack of any additional treatment I could possibly providefor trauma and the limitations of field imaging (e.g. x-rays), I’ve been treating him as a presumed P. tenuis larva migrans case with antiparasitics, anti-inflammatories and nursing care. I could have done a spinal tap to try to confirm my suspicion, but if it was unremarkable I still wouldn’t rule out P. tenuis, so I’d still treat him. Given the hassles of performing a spinal tap and the limited likelihood that I’d find a different cause, I didn’t bother. (If he was in hospital where it was easier and more convenient, I’d likely have done it, as it would be interesting to know the results.)

Drugs are part of the treatment for this disease, but nursing care is a huge component. Any down large animal is always a concern, as they can damage their muscles and nerves lying down for too long simply because of their weight. Fortunately, alpacas are much lower risk for complications from short term recumbency given their smaller size. However, I still need to keep him in a well bedded area and move him around so that he’s changing positions and not laying in wet (urine soaked) bedding. That also helps reduce the risk of pressure sores, another major concern in recumbent animals.

Over the past few days, he’s been up and down (figuratively and literally). Most days, I can get him up with some assistance and he’ll take a few steps with me supporting and steering him by holding his tail. Some days have been better than others.

With any neurological disease, the first thing I want to see is that the animal stops deteriorating. If the animal just keeps getting worse, the prognosis is really bad. Mickey plateaued pretty early, which was a good start.

Yesterday, I tried him in an ad hoc sling I made from a repurposed hammock. It wasn’t much of a success since he didn’t try to stand. A sling can be good to get an animal off their feet and let them use their limbs, with support. But Mickey didn’t use the sling like that, he just hung there, so there was a risk the sling would just cause more damage. It was a nice try, but I abandoned it, at least for now.

This morning, Mickey got up with assistance and took the most steps he’s made so far, walking from the barn to a run-in shed/barn. Movement is good, but walking on ice is bad. However, there was a pretty good path for him and the shed is well bedded, so I let him lead the way and that was his spot for a while.

The video below is from this afternoon – his strongest effort yet, but still with some pretty obvious major abnormalities.

What’s the prognosis for Mickey?

I keep waffling on that. Milestone #1 was when he stopped deteriorating. Now we need to see how he improves. Neurological damage is slow to improve, and the degree of improvement is hard to predict. As long as he keeps improving, there’s hope. Once that initial improvement plateaus, I don’t expect major improvement after that. Animals with neurological damage can still improve a bit at that stage, probably in part by learning how to compensate for their deficits, but we don’t expect to see a dramatic improvement later on.

I’d like to think he’s still in the improvement phase. It’s hit and miss; he’ll look good one time and then bad a little later… that’s life managing neurological disease. But he’s showing enough improvement and is otherwise stable enough that he’s worth treating. The video from today is by far the best he’s been so that’s encouraging.

He didn’t like me much before and he’s definitely not a fan now given all the poking, prodding and medicating, but that’s life with livestock. More updates to come (good or bad).

Life cycle figure from:

As awareness of canine infectious respiratory disease complex (CIRDC, formerly known as “kennel cough”) has spiked recently, there are more discussions happening about respiratory vaccines in dogs. A large number of different bacteria and viruses play a role in CIRDC. We can vaccinate against a few of them including parainfluenza virus (the most commonly diagnosed contributor to CIRDC), the bacterium Bordetella bronchiseptica (typically number 2 or 3 on the list of diagnosed contributors), canine adenovirus (pretty uncommon) and canine influenza (very sporadic).

We also have different ways to vaccinate dogs, specifically use of injectable versus mucosal (oral or intranasal) vaccines.

  • Injectable vaccines tend to induce a better systemic antibody responses. Mucosal vaccines provide a better local immune response at the mucosal surface. For respiratory infections, the local immune response is probably the most effective. There’s reasonable evidence that mucosal vaccines are superior to injectable vaccines for Bordetella. We don’t have good data for parainfluenza, but I’d assume the same applies. (We only have injectable influenza vaccines for dogs.)
  • Mucosal vaccines are modified live organisms – versions of Bordetella and parainfluenza that are still alive (i.e. functional) but have been attenuated so that while they can elicit an immune response, there is negligible risk of causing disease in the animal. We never say a modified live vaccine (MLV) is 100% guaranteed not to cause disease, but the risk is really low, and the protection is really good, so overall they’re beneficial for vaccination in “normal” animals. However, we tend to avoid MLVs in immunocompromised animals because low virulence organisms might be more likely to cause disease in an individual with a compromised immune system.

That’s the dog side. But, we have to remember that each dog is attached to one or more people too. When we vaccinate a dog with a mucosal vaccine, it sheds the modified bacterium/virus for a while, and might have a large load of the vaccine strain in their nose or mouth right after the initial administration.

That means people can be exposed to the vaccine strains as well. Generally, that’s not a big deal, and it’s really only a potential issue for Bordetella (because canine parainfluenza and canine adenovirus of any form don’t infect people). I get asked about this a lot, by both veterinarians and pet owners, and I write a similar post to this one every few years, but each time we have a bit more data.

Why is there concern about human exposure to Bordetella in canine vaccines?

  • Bordetella bronchiseptica can cause infections in people. They are rare, but they occur. So, if the “normal” Bordetella bronchiseptica can cause disease in people, we have to think about whether the vaccine strains can cause disease too.
  • The answer is “yes,” with a big “but” (actually, a series of “buts”).

Yes, there have been a couple of reports of human infections with canine vaccine-strain Bordetella, some of which are more convincing that others.

A recent report (Kraai et al. 2023) described vaccine-strain Bordetella bronchiseptica infection in a 43-year-old woman who was taking immunosuppressive medication.

  • She developed bronchitis with malaise and a mild fever two weeks after her dog had received an intranasal vaccine.
  • Bordetella bronchiseptica was isolated from her sputum. When it’s gene sequence was assessed, it was consistent with the vaccine strain.
  • She had mild disease and responded to antimicrobial treatment.

Clearly there is some risk with human exposure, that’s certain. Some groups have said to avoid MLVs in animals living with immunocompromised people. But let’s thing about that critically for a moment. All vaccination decisions require consideration of the costs (risks) versus benefits:

  • The risk to humans from canine vaccines is really low. Millions of doses of mucosal vaccines are given to dogs every year, yet human infections are still extremely rare.
  • Disease that has been reported in people who do get sick is mild.
  • Mucosal vaccination is superior to parenteral vaccination, and prevention of disease in dogs can also reduce the risk of exposure to the “wild type” (non-attenuated) strains of Bordetella in humans.

Broad “don’t use modified live vaccines in animals owned by high risk people” statements overlook a few big-picture issues:

  • The big one is the vaccine strain is much less likely to cause disease than the circulating (non-attenuated, disease causing) strains. A person is much more likely to be infected with the Bordetella from a naturally infected dog than from a vaccinated dog, so I’d rather prevent the dog from getting infected by vaccinating with the most effective method available.
  • Natural Bordetella infection (unlike vaccination) also tends to make the dog cough, which increases human exposure to any number of bugs in the dog’s respiratory tract.
  • If that dog needs treatment with antimicrobials, we run the risk of the person being exposed to antimicrobial resistant bacteria, some of which can pose additional risks to people.
  • Antimicrobials also increase the risk of the dog developing diarrhea, which can greatly increase human exposure to disease-causing bacteria in feces (especially if the dog poops on the floor).

Some more food for thought:

If I have a dog that was recently vaccinated with a mucosal vaccine, and I was asked to rank the top 5 zoonotic pathogens that are in the dog, vaccine-strain Bordetella wouldn’t even crack that list. There’s a mix of potentially disease-causing bacteria in every dog, all the time. Getting tunnel vision about one in particular, especially one that’s really quite low risk, is not helpful.

What about killed, injectable Bordetella vaccines?

Injectable killed Bordetella vaccines (which contain no live organisms, as the name suggested) do work, they just don’t work as well. If there’s significant concern from the owner, or some other unusual circumstance that makes use of a mucosal vaccine undesirable, then by all means, use an injectable vaccine. I’d consider that to be a rare situation.

Also bear in mind that killed “kennel cough” vaccines are just for Bordetella. They don’t include anything for parainfluenza virus, the most common cause of CIRDC. Parainfluenza is part of common combination “core” vaccines (e.g. DA2PP), but those vaccines don’t do a great job of protecting against paraflu. So, while an injectable Bordetella vaccine removes the risk of exposure to vaccine-strain Bordetella, it offers less protection against Bordetella and none against paraflu, so we have greater risk of disease in the dog overall, and the implications described above that come with it.

Let’s be clear: There’s never a zero risk situation when it comes to exposure to infectious bugs (from vaccination or pet ownership in general). We have to consider the risks and benefits in every situation.

But, almost always, for high risk households, I support vaccination whenever the dog’s lifestyle and risk factors indicate that Bordetella vaccination is warranted. I’d stick with mucosal vaccines for respiratory diseases whenever possible, since they provide much better protection and we can easily mitigate the very low risk from the vaccine. Those mitigation measures include:

  • Keeping the owner outside of the exam room when the dog is vaccinated.
  • Wiping the dog’s nose/mouth after vaccination to remove any major external contamination.
  • Recommending that the owner avoid direct contact with the dog’s oral and nasal secretions. That’s particularly important for the first 24 hours after vaccination, but it’s something I’d recommend for a high risk owner to always avoid.
  • Being diligent about routine hygiene practices (e.g. handwashing), especially after contact with the dog’s face (again, something that’s actually always important for a high risk owner).

Photo credit: Dr. Kate Armstrong (from Weese & Evason, Infectious Diseases of the Dog and Cat, A Color Handbook)

In the first two parts of this series, I explained a lot of the changes that have been made to the CLSI veterinary antimicrobial susceptibility testing guidelines, specifically those related to staphylococci and Enterobacterales (which includes E. coli and friends).  There’s less to say about Pseudomonas, but these changes will impact our use of the already limited range of available antimicrobials for this vexing bacterial genus.

New antimicrobial susceptibility breakpoints for Pseudomonas

Most veterinarians don’t realize that we don’t have established, species-specific breakpoints for many bug/drug combinations. The breakpoints veterinary labs use to call a bug susceptible or resistant to an antimicrobial are often extrapolated from other species and/or drugs. That probably works reasonably well most of the time, but not all the time. Species-specific breakpoints that are based on an understanding of the drug pharmacokinetics in that species are needed to have more confidence in the antimicrobial susceptibility testing results.

Breakpoints for enrofloxacin and marbofloxacin are now available for Pseudomonas isolates specifically from dogs. Previously, labs presumably chose a breakpoint for these isolates based on human fluoroquinolone breakpoints, the canine levofloxacin breakpoints, or the feline enrofloxacin breakpoints.  All of those are higher than the new canine breakpoints for these drugs. As a result, some bacterial isolates that would have previously been reported as susceptible will now be reported (more accurately) as resistant. This will seemingly reduce treatment options in some cases, but it’s actually a good thing, because we can have more confidence using these drugs for infections that are reported as susceptible, and should have fewer treatment failures.

New susceptible, dose dependent (SDD) breakpoints for Pseudomonas in dogs

This new breakpoint classification approach has been implemented for Pseudomonas and enrofloxacin and marbofloxacin. It’s based on recognition that we can often safely use higher doses of these drugs (at least in dogs), which we can use to overcome some degree of resistance:

Canine breakpoints for enrofloxacin and Pseudomonas

CategorySusceptible (5 mg/kg)SDD: 10 mg/kgSDD: 20 mg/kgResistant
MIC<0.06 ug/ml0.120.25> 0.5
  • 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, the bug is susceptible at a dose of >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)

If the MIC is <0.5 ug/mL, I’d only treat at 20 mg/kg. The bug might be susceptible to a lower dose, but we don’t know.

If the MIC is reported as <4, <2, <1 or <0.5 ug/mL, we’re screwed. We need to know that the bug has an MIC or no greater than 0.25 ug/mL in order for treatment with enrofloxacin to be effective, and none of those MICs tell us that clearly – the bacterium could still be susceptible or resistant. I would not use enrofloxacin in these cases.

Canine breakpoints for marbofloxacin and Pseudomonas (pretty similar)

CategorySusceptible (2.75 mg/kg)SDD: 5.5 mg/kgResistant
Minimum inhibitory concentration (MIC)<0.120.25> 0.5
  • 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 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 MIC is <0.5 ug/mL, only treat using a dose of 5.5 mg/kg. The bug might be susceptible to 2.75 mg/kg, but we don’t know.

If the MIC is reported as <4, <2, or <1 ug/mL, we don’t know if the bug is actually susceptible or resistant, so I would not use marbofloxacin.

There are also no disk diffusion breakpoints for these drugs and Pseudomonas, so we need the MIC data (which is based on broth microdilution) to determine susceptibility.

These changes will be disruptive but are important, because under the old guidelines labs are reporting a lot of bugs as susceptible when they really aren’t, or when higher drug doses are needed to treat effectively. It will take time for labs to implement the changes to their testing and reporting. In the interim, we need to look at the actual MIC, not just whether the lab classified the bug as susceptible or resistant under the old guidelines. Since labs may not test a wide range of drug concentrations, we’re going to have situations where we can’t properly interpret the results, at least until the labs make the necessary changes.