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Why carbapenemase-producing CRE raise the bar

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Anne Ford

March 2018—When Stephen Brecher, PhD, compares MRSA to carbapenem-resistant Enterobacteriaceae, the figures of speech come fast and furious.

“We are not in Kansas anymore,” he said. “The bar has been raised. I consider MRSA a picnic compared to CP-CRE [carbapenemase-producing CRE].”

Detection of carbapenemases

Dr. Brecher is director of microbiology and “chief of staph,” as he puts it, at the VA Boston Healthcare System and an associate professor of pathology and laboratory medicine, Boston University School of Medicine. Microbiology laboratories are the radar system needed to detect and prevent the spread of CP-CRE, Dr. Brecher says, and failure to do so would be catastrophic. There are concerns about using new, expensive tests, he acknowledges. But “the most expensive test is the one that does not work or takes too long to work.” Go to administration: “Plead your case to get the best technology available to do your job,” he says.

carbapenemase_Fig1Dr. Brecher spoke last fall on CP-CRE (carbapenemase-producing carbapenem-resistant Enterobacteriaceae), beta-lactamases, and antibiotic breakpoints in a webinar hosted by CAP TODAY and made possible by an educational grant from Cepheid. His co-presenter, Lars Westblade, PhD, of NewYork-Presbyterian/Weill Cornell Medical Center, spoke on the phenotypic and genotypic tests used to detect CP-CRE. (See page 16.)

Carbapenemases are enzymes that break down the structure of carbapenem antibiotics, of which there are four on the market: imipenem, mero­penem, doripenem, and ertapenem. “We now have at least 500 different carbapenemases,” Dr. Brecher said, noting that resistance can be mediated by mechanisms other than through the carbapenemases.

Some places in the United States have had a lot of CP-CRE, but many places have seen very little. “Our goal has to be to keep it that way,” he said.

Consider this: With MRSA, there is one organism and one main resistance gene (mecA). It is relatively easy to grow Staphylococcus aureus and relatively easy to detect resistance, large segments of the population can be screened with a comparatively noninvasive anterior nares swab, and there are FDA-cleared chromogenic agars and nucleic acid amplification tests.

In contrast, “With CP-CRE, we have multiple organisms and multiple resistance genes. Although the organisms are usually easy to grow, it’s not always easy to detect resistance. When we do have carriers—and we don’t even know the actual carrier rate—detection is from a rectal swab, which is clearly more invasive than an anterior nares swab. There are no FDA-approved screening agars. There is an FDA-approved nucleic acid test” for about 90 of the most common of these genes in five main groups—KPC, NDM, VIM, OXA, and IMP. Antibiotic treatment can vary by class/type of carbapenemase.

The Centers for Disease Control and Prevention defines CP-CRE as Enterobacteriaceae that are resistant to imipenem, meropenem, doripenem, or ertapenem, or documentation that the isolate possesses a carbapenemase. “I respect the CDC but have a problem with their definition because it includes ertapenem,” Dr. Brecher said. “Ertapenem can be a marker for CP-CRE, but it has poor specificity and you’re going to get false-positives. That translates into time, money, and infection prevention dollars.”

The 2017 Veterans Affairs guidelines focused on E. coli, Klebsiella, and Enterobacter and left ertapenem and other Enterobacteriaceae out of the definition. “I am interested in other organisms as well, but just as thieves rob banks because that’s where the money is,” Dr. Brecher said, “our efforts really have to be at the big three.”

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