Human CRE infections are 'untreatable,' experts say

This spring, the director of the U.S. Centers for Disease Control and Prevention (CDC) called carbapenem-resistant Enterobacteriaceae (CRE) a "nightmare bacteria." "Our strongest antibiotics don't work, and patients are left with potentially untreatable infections," said Tom Frieden, MD, MPH, in a press release.

In the first half of 2012, nearly 200 U.S. healthcare facilities treated at least one patient infected with this new super breed.1 In a National Public Radio interview, the CDC's Michael Bell, MD, said, "This particular type of resistance has seemed to spread from one type of bacteria to another. It's able to hand off its blueprint for resistance to other types of bacteria, which raises the possibility that this kind of untreatable infection could become much more commonplace."

These types of bacteria don't get into human patients simply because of compromised immune systems, said Brad Spelberg, MD, of Harbor-UCLA Medical Center, in the same broadcast. "It's because we're providing very intensive care: putting plastic catheters into their bloodsteams so we can give life-saving medicines, inserting tubes into their lungs so we can have mechanical ventilators breathe for them or placing tubes in their bladders," he said. "When you break those types of anatomical barriers, it allows bacteria that normally don't get into those parts of your body to get in there."

Veterinary concerns

Fortunately, CRE have not been reported in dogs and cats to a great extent, if at all, says Jane E. Sykes, BVSc (Hons), PhD, DACVIM, of the University of California Davis School of Veterinary Medicine. Sykes is a member of the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases (ISCAID). "To our knowledge, we have never detected them here in our companion animal patient population at UC Davis."

However, the rate of resistance in other bacteria that infect dogs and cats has increased to scary proportions. In particular, Sykes has seen a dramatic rise in multidrug-resistant Staphylococcus pseudintermedius infections and infections by Enterobacteriaceae (Escherichia coli, Klebsiella) and Pseudomonas aeruginosa. "Methicillin-resistant Staphylococcus pseudintermedius infections can be resistant to almost every orally administered drug available, and these can be particularly serious when they cause orthopedic infections, such as tibial plateau leveling osteotomy infections," she says.

Some of these resistant bacteria, especially the gram-negative organisms, may also have the potential to colonize humans that are in contact with these pets, Sykes continues. "More than ever before, veterinarians need to be prudent in regard to antibiotic use and hospital infection-control protocols," she says.

Taking precautions

In terms of preventing antibiotic-resistant organisms from infecting pets, veterinarians should institute the same basic precautions they would use for any infectious disease, says Mark Papich, DVM, MS, of North Carolina State University's College of Veterinary Medicine. When they identify an infection within an animal, veterinarians and their staff need to be cautious about spreading it from one animal patient to another or to themselves. "Basically, they should practice good normal hygiene," Papich says. "Routine hygiene, washing of hands, is probably the biggest component."

Patients known to be infected with multidrug-resistant bacteria such as CRE should be treated with strict isolation protocols to prevent spread within the hospital environment.

"We always recommend judicious use of the antibiotics that practitioners prescribe," Papich says. "Don't use an antibiotic when it's not indicated, and don't use antibiotics for longer than necessary. That's just part of good antibiotic stewardship and is essential to practicing good-quality veterinary medicine."

Sykes offers some key thoughts regarding antimicrobial selection and use:

1. Test. Whenever possible, verify the presence of a bacterial infection using cytologic examination and bacterial culture before starting antibiotic treatment.

2. Identify primary conditions. Always attempt to identify and treat the underlying cause of a bacterial infection—such as allergic dermatitis in dogs with superficial pyoderma or recessed vulva in dogs with recurrent urinary tract infections (UTIs)—rather than just treating the infection with antibiotics. Treatment with antibiotics without addressing the underlying cause can select for resistance.

3. Target treatment. Select the most narrow-spectrum antibiotic based on cytologic examination, bacterial culture and susceptibility results or a knowledge of organisms that normally cause infections at a particular site. Choose an antibiotic known to be active at the site of the infection.

4. Follow protocol. Be diligent about hand washing (wash all surfaces of the hand and wrist for at least 15 seconds) and wear gloves for procedures involving non-intact skin to prevent nosocomial infections. Using hand sanitizer can help improve compliance. These routine precautions should be practiced before and after handling each patient.

Sykes' Antimicrobial Working Group is working on guidelines for treating common bacterial infections in companion animals because of the emergence of multidrug-resistant bacteria. The UTI guidelines can be found on the society's website at iscaid.org.

Because of heavy antimicrobial use in treating canine and feline UTIs, veterinarians must be aware of how inappropriate treatment contributes to the emergence of multidrug-resistant pathogens, the working group says. At the same time, prudent (and therefore rare) use of certain drugs would constitute a minuscule fraction of overall use. As such, using critically important antimicrobials in companion animals can be justified as long as their use is prudent and proper and based on bacterial culture and susceptibility data as well as patient care and welfare factors. In particular, the use of vancomycin, the carbapenems and linezolid is not justified unless the following criteria are met, the working group says:2

(1) Infection is documented based on clinical bacterial culture results and cytologic abnormalities. (2) Resistance to all other reasonable options and susceptibility to the chosen antimicrobial are documented. (3) The infection is potentially treatable. The use of critical drugs in situations in which there is little realistic chance of eliminating the infection (e.g., failure to remove the underlying cause) is not supported. (4) Consultation with an infectious disease and antimicrobial therapy expert has been obtained to determine if there are any other viable options.

A matter of time

Sykes thinks it's just a matter of time before CRE is recognized in animals. Because she and her colleagues are seeing more multidrug-resistant gram-negative bacteria, they're starting to use carbapenems such as meropenem more in companion animal medicine. "It's my concern that, as a result, we could select for CRE in veterinary patients as well," she says. "But there's a possibility that the other pathway will occur, which is that they'll become so much more prevalent in humans that we'll start seeing them colonizing pets too."

Papich says it's hard to predict how long it might take for CRE to affect veterinary patients. "Bacteria don't see any boundaries between species," he says. "Eventually these highly resistant pathogens infecting humans get transferred to our animals, and we end up with a similar problem."

J. Scott Weese, DVM, DVSc, DACVIM, of the University of Guelph's Ontario Veterinary College, says he has received anecdotal reports of sporadic CRE infections in animals, mainly out of the southern United States. "The saving grace for us at the moment is that CRE has not established much of a foothold yet in people in the community, but if or when it does, that means there will be exposure of animals," he says. "And given the broad range of bugs that can acquire resistance genes and their potential as enteric commensals, it certainly could spread in the animal population."

Papich says veterinarians who suspect CRE should use a laboratory that adheres to standards established by the Clinical Laboratory Standards Institute (CLSI; see clsi.org). "Although we do not have specific guidelines for testing animals at this time, laboratories should use the human testing standards," Papich says. At a CLSI meeting this month, a special workshop will meet to develop guidelines for veterinary diagnostic laboratories.

Take-home message

Whatever happens, the emergence of CRE has given the veterinary community an opportunity to discuss the importance of rational antibiotic use and hospital infection control practices. "We have to remember that indiscriminate antibiotic use in an individual patient, when it is done by thousands of other veterinarians and over the course of time in many animals, can actually be to the detriment of all of our patients in the future," says Sykes.

Papich agrees. "It is an important concern because we have so few antibiotics left to treat these infections," he says. "We do use the carbapenem antibiotics in companion animals. They have such a good spectrum of activity that veterinarians rely on them when there are few other antibiotics that are effective."

References

1. CDC warns of 'nightmare' bacteria killing hospital patients. Available at: www.everydayhealth.com/healthy-living/cdc-warns-of-nightmare-bacteria-killing-hospital-patients-7185.aspx.

2. Weese JS, Blondeau JM, Boothe D, et al. Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. Vet Med Intl 2011.

Suggested reading

CDC. Guidance for control of Carbapenem-resistant Enterobacteriaceae (CRE). 2012 CRE Toolkit. Available at: www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdf.