Two investigations reveal how resistant bacteria may have spread from pets to people
The paper describes two separate investigations that were
ultimately linked through epidemiologic and molecular detective work. One
investigation began at a veterinary teaching hospital in Worcester County,
Massachusetts, where a cluster of carbapenemase-producing Escherichia
coli infections were detected in cats and dogs in late 2022, a first
for the practice. The other involved a cluster of human infections that
occurred months later in the same county, caused by the same bacteria.
For months, there were no known links between the two
investigations. But molecular analysis of bacteria samples from the two
investigations eventually uncovered links that would reveal a hidden One Health
connection.
"Once we put the isolates into the same database,
that's when we discovered that they all clustered together," coauthor
Stephen Cole, DVM, an assistant professor of clinical microbiology at the
University of Pennsylvania's School of Veterinary Medicine, told CIDRAP News.
A growing veterinary problem
Carbapenemase-producing Enterobacterales (CPE) are
multidrug-resistant pathogens that are known to primarily cause
difficult-to-treat and sometimes deadly infections in hospital patients.
They've been labeled a high-priority pathogen by both the
World Health Organization and the US Centers for Disease Control and Prevention
(CDC). A recent report by the CDC highlighted the increase in CPE hospital
infections in the United States over the last 5 years, with a dramatic increase
observed in CPE-carrying NDM (New Delhi metallo-beta-lactamase) genes.
But there is concern that CPE have begun to spread beyond
hospitals and into community settings, because the carbapenemase enzymes that
inactivate carbapenem antibiotics are carried on mobile genes that can be
shared between bacterial strains and species, enabling increased transmission.
There have also been sporadic reports of pets with CPE colonization and
infections.
Coauthor Ian DeStefano, DVM, an assistant clinical professor
at Tufts University's Cummings School of Veterinary Medicine who was involved
in the veterinary investigation, said he believes CPEs are an emerging problem
in veterinary medicine. But the average veterinarian knows little about them
and has likely never come across one.
"I think there are also instances where vets find
isolates that probably are CPEs and just don't know that's what they're looking
at," he said.
At the veterinary teaching hospital where the CPE outbreak
was identified, further investigation conducted in coordination with the
Massachusetts Department of Public Health (MDPH) identified environmental
contamination on hospital surfaces and colonization in hospitalized
animals.
Once we put the isolates into the same database, that's
when we discovered that they all clustered together.
Isolates from hospital surfaces, dogs, and cats were then
sent to Cole and colleagues at the University of Pennsylvania's Carbapenem
Resistant Enterobacterales Animal Testing and Epidemiology (CREATE) lab for
further testing. Whole-genome sequencing (WGS) of the isolates was performed by
the Minnesota Department of Health.
Months later, a separate investigation by the Massachusetts
State Public Health Laboratory was undertaken to examine potential links
between three people who had urinary tract infections caused by the same type
of CPE identified at the veterinary hospital—blaNDM-5-harboring E
coli. The three case-patients (a 79-year-old woman, a 63-year-old man,
and a 23-year-old woman) all lived in Worcester County but had no epidemiologic
links such as common healthcare exposure, recent foreign travel, or medical
tourism.
"There seemed to be three human isolates that were
super related to one another, but it was unclear how the people were,"
DeStefano said.
The answer became clear after the sequenced isolates from
the two investigations were uploaded to the National Center for Biotechnology
Information (NCBI) Pathogen Detection database and the results were analyzed at
the CREATE lab. The human, animal, and environmental isolates all clustered
within 0 to 10 single-nucleotide polymorphisms—an indication they were highly
related to one another.
"There was a whole-genome sequencing project over here
on people and another over here on animals," said Cole. "And our
ability to data share really helped us identify this sort of cryptic connection
between the two that you wouldn't have found without doing that."
Though initial interviews of the three patients with CPE
infections failed to identify any epidemiologic links between them, the
sequencing results prompted follow-up interviews, which found that all three
patients had pets in their homes who had received care at the veterinary
hospital in the months leading up to their infections.
Although the animals were never screened for CPE, DeStefano
said the genetic results, interviews, and timeline of events indicate they had
received care at the veterinary teaching hospital when it was experiencing its
CPE outbreak. They likely became colonized with the bacteria at the hospital
and then spread it to their owners.
"The timeline fits with them being hospitalized at the
same time that we were having a CPE problem, and that predated the pet's owner
then becoming sick or having some sort of CPE isolate later found,"
DeStefano said. He also noted that, since transmission can go both directions,
it's possible that the CPE outbreak at the veterinary hospital originated with
a pet whose owner was colonized with CPE.
"To me, it's the definition of One Health," he
added.
Collaboration needed across human, veterinary health
sectors
Previous studies have suggested the potential for
transmission of resistant bacteria between companion animals and their owners.
A 2019
study that analyzed bacteria samples from Dutch pet owners and
their pets found a handful of households where drug-resistant E coli isolates
carried by dogs and their owners were nearly identical.
But Cole says most of those studies involve colonization and
often lack epidemiologic context. Their paper, on the other hand, describes a
targeted investigation that revealed the hidden epidemiology behind clinically
relevant bacteria that were causing infections. And both he and DeStefano
believe that it highlights the need for the human and veterinary health sectors
to work together to limit the spread of a significant public health threat.
"Given the contact between large numbers of animals at
dog parks, veterinary hospitals, and boarding facilities, the potential for
amplification of pets and humans exposed [to CPE] is significant and could
result in sporadic cases, clusters, or outbreaks," they and their
colleagues wrote in the paper.
To me, it's the definition of One Health.
What would this look like in practice? For one, it would
require more real-time surveillance of CPE in veterinary settings and the
environments that pets and their owners share and collaborations between state
public health departments and animal health authorities to leverage testing
infrastructure. They also suggest that human health practitioners include
companion animals when considering possible sources of drug-resistant
infections.
"We know that this is not an isolated incident, and
unfortunately, I don't see this problem going away," said DeStefano.
That sentiment is shared in an accompanying editorial by
researchers from the University of Bern in Switzerland, who say the findings
from this investigation and others "underscores an alarming One Health
concern from the veterinary clinics which needs to be addressed rapidly."
"Incremental efforts across this and other sectors may
contribute to curbing the rapid dissemination of CPE into the human and animal
populations and prevent the uncontrolled rise of avoidable infections,"
they wrote.
Although he acknowledges that such efforts will require a
level of funding and support for public health that's currently in short supply
in most states, Cole said he sees a "golden opportunity" to protect
human and animal health.
"We know pets help us live happier, healthier lives in
general," he said. "So AMR [antimicrobial resistance] is not just a
threat to the health of people, it's a threat to the health of our pets, too.
And we can combat it."
