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.