One Health, wicked problems, and carbapenem-resistant E. Coli: Penn Vet weathers the perfect storm

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When researchers at the University of Pennsylvania Matthew J. Ryan Veterinary Hospital (Penn Vet) shipped off a set of animal isolates to the US Food and Drug Administration (FDA) for testing at the end of 2018, it was business as usual.

The results they got back were anything but: In April of 2019, the FDA’s Veterinary Laboratory Information and Response Network (Vet-LIRN) informed Penn Vet that among those isolates were samples from a family of carbapenem-resistant Enterobacteriaceae (CRE) that includes Escherichia coli (E. coli) taken from a handful of dogs and one cat they’d treated the previous summer.

This was unusual because none of the infected animals had ever been treated with carbapenems, which led the Penn Vet team to suspect that Vet-LIRN might eventually find a carbapenem-resistance gene in the E. coli isolate.

Penn Vet is part of a network of veterinary labs across the country that regularly submits animal isolates to the FDA’s Vet-LIRN for antibiotic-resistance surveillance and genome sequencing.

And Vet-LIRN found a gene, but not one anybody was expecting.

Vet-LIRN identified the gene as New Delhi metallo-beta-lactamase-5, or NDM-5, a gene that confers elevated resistance to carbapenems. In the US, the gene has been detected in only a few human E. coli infections and never in companion animals. In fact, only a handful of cases in dogs have ever been reported worldwide.

Which makes the clutch of cases at Penn Vet something of a puzzle.

NEWStat reached out to Shelley Rankin, PhD, a professor of clinical microbiology and head of Diagnostic Services at Penn Vet to find out more.

Rankin told NEWStat that Penn Vet is no longer in an active outbreak phase. “We rapidly identified cases and performed environmental surveillance to identify a source, or sources,” Rankin said. Penn Vet already had an active infection prevention program in place, and during the outbreak they worked closely with the Philadelphia Department of Public Health to review their policies and procedures and make sure they didn’t miss anything. “We initiated whole-hospital environmental surveillance culturing to try and identify places or things that could be a source of infection and eliminate them.”

It worked: the total number of cases topped out at 15, and all animals are doing fine.

Rankin and her colleagues are still looking for answers. Rankin called the outbreak as “the quintessential One Health wicked problem.” Wicked problems are essentially problems that have no easy solution—solving one part may compound another.

For example:

To begin with, Rankin said, the pathways of infection are complex: these bacteria colonize the gastro-intestinal tract of humans and animals and are transmitted via the fecal/oral route and also by direct and indirect contact, Rankin said. That means both humans and animals are discharging CRE into the environment as sewage waste and as trash (just picture the typical pet owner casually tossing their pet’s poop bag in the nearest dumpster).

Never mind the possibility that humans and animals are contaminating the environment via infected hands, shoes, paws, and clothing.

Rankin said the sheer number of unknowns can be daunting: “We have no real knowledge of transmission rates between animals, in the hospital or in the street; between humans, in the hospital or in the community; or from animals to humans [and] humans to animals.”

“Bacteria that are resistant to all antimicrobial classes are very difficult to control or eradicate,” Rankin added. “How do you practice good antimicrobial stewardship for an organism that is resistant to all of your choices?”

Meanwhile, Rankin and her team are working hard to figure out where the animals acquired the CRE, although the answer is proving elusive.

“We have no idea yet how the first animal became colonized with this unique NDM-5 E. coli,” she said, but adds that “We’ve performed a case control study and have identified a likely source of transmission within the hospital, and also some risk factors.” But for the moment, Rankin’s keeping that information under her hat: Her team will present their analysis at the Society of Healthcare Epidemiology of the Americas (SHEA) Conference in Atlanta in March. “We look forward to sharing those results with the veterinary community.”

In the meantime, Penn Vet continues to screen for the infection, testing all animals admitted to the hospital for 24 hours or more and testing again upon discharge.

“We screen feces from animals using the gold-standard PCR [polymerase chain reaction] test for the detection of carbapenem-resistance genes. Results are available within an hour,” Rankin said. “All animals who screen positive for GI colonization are confirmed by culture, and we’ve been doing whole genome sequencing on the organisms isolated in collaboration with Vet-LIRN.

Meanwhile, Rankin says the profession should brace itself for the possibility of this particular CRE popping up other places.

Rankin points out that veterinary medicine is a complex healthcare network that sees animals moving between hospitals for many different reasons, as do humans associated with the profession. And that’s a lot of potential avenues of transmission: “I think it is likely that animals infected or colonized with CRE will be found across the country, if we look for them.”

Photo credit: © iStock/Sproetniek