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

Category	Susceptible (5 mg/kg)	SDD: 10 mg/kg	SDD: 20 mg/kg	Resistant
MIC	<0.06 ug/ml	0.12	0.25	> 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)

Category	Susceptible (2.75 mg/kg)	SDD: 5.5 mg/kg	Resistant
Minimum inhibitory concentration (MIC)	<0.12	0.25	> 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.