Change is tough. Repeated changes are even tougher, especially when it takes a lot of time and effort for each one to be understood and implemented. But change is also good – and important – when it improves how we do things.

In 2024, the Clinical and Laboratory Standards Institute (CLSI) changed some important breakpoints for antimicrobial susceptibility testing in dogs. Breakpoints are what labs use to to report whether a bacterial isolate is susceptible or resistant to different antimicrobials. As we learn more about the bugs and the drugs and how they interact, sometimes those breakpoints need to be adjusted, so that the veterinarian receiving the report is getting the most accurate information possible to make better treatment decisions for the animal. That’s good. But it also involves change, which can be slow. It’s taken close to two years for some labs to fully implement the 2024 changes.

Now we have data suggesting more things need to change. CLSI hasn’t updated any mrore breakpoints (yet), but published data indicate that we should probably be rethinking how we’re interpreting certain antimicrobial susceptibility test results for cats.

A recently published study (Papich et al. 2025) came to the conclusion that that breakpoints for fluorquinolone antibiotics for some bacterial isolates from cats should be lowered. That means some bacteria that would currently be reported as susceptible should actually be considered resistant. It’s very similar to the changes that were made in 2024 for isolates from dogs; I suspected at the time a similar change would eventually be needed for feline isolates, but it hadn’t yet been studied enough.

The researchers examined pharmacokinetic data, pharmacokinetic-pharmacodynamic (PK/PD) analysis and susceptibility data from a large number of bacterial isolates to determine the appropriate breakpoints for enrofloxacin and marbofloxacin when it comes to Enterobacterales (E. coli and related bacteria), Pseudomonas aeruginosa, Staphylococcus spp., Pasteurella multocida and Streptococcus. Skipping to the punchline, what they found indicated that we should be using lower breakpoints for these bug-drug combinations in cats. The current breakpoints would classify certain isolates as susceptible to these drugs, when in fact the likelihood of achieving adequate inhibitory drug levels in the target tissues using standard dosing was very low.

Here is a summary of the old (technically still current) and suggested new breakpoints for these bug-drug combinations in cats:

They also suggested a “susceptible dose dependent” (SDD) breakpoint, as was done for dogs. This means that the bacterium can be considered susceptible when a higher dose of the drug is used in the patient. For marbofloxacin, isolates that meet the SDD breakpoint are only considered susceptible when the cat is dosed at 5.5 mg/kg (the high end of the label dose for this drug). There are no SDD breakpoints for enrofloxacin because we don’t want to use higher doses in cats due to the risk of causing blindness (retinopathy). Personally, I have no use for enrofloxacin in cats at all because of this risk. but if it’s going to be used, we don’t want to go beyond 5 mg/kg regardless, so there’s no SDD breakpoint.

What do we do now?

• We have data suggesting that we need new breakpoints, but the CLSI standards haven’t yest been changed.
• Personally, I’ll start using the new breakpoints right away. I trust the research group and the data, and the new breakpoints are consistent with the change that was made for canine isolates.
• When we get MIC data directly on our lab reports, it’s easy to apply the breakpoints ourselves. The challenge is when labs only test a narrow range of drug concentrations or don’t report MICs (i.e. the report doesn’t provide the number, just susceptible intermediate or resistant (S-I-R)). Then we’re a bit stuck, and my confidence in using enrofloxacin or marbofloxacin would decrease.

Pradofloxacin, the newest licensed fluoroquinolone in cats (and dogs in some countries), was not included in this study. The breakpoints for this drug were not changed for dog isolates in 2024 either. Whether that’s because the newer breakpoints for pradofloxacin are fine, or there isn’t enough data to re-assess them, or it was just lower priority to study isn’t clear, but it raises questions. If I see an isolate that is resistant to marbofloxacin and enrofloxacin based on the new breakpoints in dogs (or the suggested new breakpoints in cats), and it’s classified as “susceptible” to pradofloxacin but right at the breakpoint, I’d be wary of using it. It might work perfectly fine, but it gives me a bit of pause, and I’d be inclined to look at other options.

I’ve been meaning to write about this for a few days, but a case from today prompted me to finally do it. It was a cat with an E. coli infection that was reported as susceptible to fluoroquinolones, but looking at the MICs and this paper, I’m not confident that it actually is. So, I recommended a different drug. I actually would have recommended the different drug anyway, since it was a lower tier option that should nonetheless be effective, but this paper changed my assessment; had my options been more limited, I would have searched for a non-fluoroquinolone option.

This paper and the new suggested breakpoints add more complication to an already complicated area, but while it can be a hassle, and change is still tough, it’s important progress. It will help veterinarians provide more effective patient care and improve antimicrobial stewardship, by avoiding using drugs that aren’t likely to be effective against specific infections in cats.