New antimicrobial resistance challenges continue to emerge. In the veterinary field (especially in small animals), we have the advantage of seeing what’s happening in human medicine first, since that’s often an early warning system for what we’re going to encounter. We’ve seen a variety of resistant bacteria first became a problem in people, and then became a problem in animals, either because of spread of the bacterium from people to pets, or because of the same inciting cause (antibiotic use) leading to development of similar issues.

Lately, we’ve been working on a lot of resistant Gram negative bacteria like E. coli. In particular, we’ve been studying E. coli (and other bacteria from the Enterobacteriaceae family) that produce extended spectrum beta-lactamases (ESBLs). These are enzymes that break down a range of antibiotics in the very commonly-used penicillin and cephalosporin classes. The bacteria also tend to become resistant to other antibiotics at the same time (by acquiring other resistance mechanisms), making them potentially even harder to treat. A common solution for for infections involving ESBL bacteria is to use drugs from the carbapenem class, such as meropenem.

Unfortunately (but not surprisingly), more use leads to more resistance. Carbapenemase-producing Enterobacteriaceae (CPE) are now a big problem in human medicine as they can be very difficult to treat, especially since some have developed resistance to other last resort drugs as well.

We’ve been looking out for these in veterinary medicine. I’ve seen a few cases, all from the US so far. We don’t use meropenem much (although it can be overused), so there’s less selection pressure in our veterinary patients. However, with more antibiotic use of any sort, rare use of meropenem and the potential spread of CPE from humans to their pets, we’ve known it’s coming.

Our concerns are highlighted but a cluster of 15 cases of CPE infection at the University of Pennsylvania’s small animal hospital. Here’s a summary of the cases from the hospital:

Fourteen dogs and one cat were diagnosed with CPE in the past year.  That’s a pretty astounding and concerning number.

  • A cluster of 6 cases was identified in their ICU in July 2018. A second cluster of 3 cases was identified in September and an additional 6 were identified through June 2019 (it’s not clear to me whether the latter group was a cluster or independent cases).
  • Infected animals were isolated as per hospital protocols.
  • Carbapenem resistance in these cases was due to a gene called NDM-5. Finding the same uncommon gene in multiple isolates of the same bacterial species suggests that these are all linked, but it’s hard to say how the different clusters relate (or if they do).
  • 13/15 infected animals were discharged from the hospital and two were euthanized because of unrelated problems. CPE is usually treatable if the diagnosis is made and a appropriate antimicrobial (and adjunct) therapy is started in a timely manner.

From a population standpoint, I’d be happy to hear that these were all linked infections. That’s not something we want to see in a hospital, but 15 linked cases would be better than 15 individual cases, since the latter would suggest there’s a lot of CPE in the community. CPE are no more likely to cause disease than susceptible Enterobacteriaceae, they’re just harder to treat when they do. Diagnosed infections presumably represent the minority of infected dogs and cats, since the bug most often lives harmlessly in the intestinal tract (and gets passed in the feces, thus creating exposure risk for other animals and people).

One concern here is what happened after discharge from the hospital. An animal with a CPE infection probably also has the bacterium living in its intestine. It’s been shown that dogs infected with ESBL-producing Enterobacteriaceae can shed the bacterium for months. We don’t know much at all about CPE shedding in dogs and cats, but it’s likely that some of these animals have been (or still are) shedding CPE.

This won’t be the last we hear about CPE in dogs and cats. Hopefully it remains a rare issue but we’re trying to figure out more about these bugs and how to limit their spread.