The terms carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant organism (CRO) are inadequate in light of new therapies, according to the authors of a paper published in Clinical Infectious Diseases,

For 25 years after imipenem’s launch in 1985, carbapenems were the most commonly used class of antibiotics for infections involving multiresistant gram-negative bacteria. However, there is a significant difference between CRO and CRE: the latter is specific to one family of bacteria. But both terms are used frequently, and often interchangeably by government and agency reports but neither are well-defined.

The study authors highlighted that it is unclear whether they include Proteeae with inherent imipenem resistance, porin-deficient Enterobacterales resistant to ertapenem but not other carbapenems, Enterobacterales with OXA-48-like enzymes that remain carbapenem susceptible at breakpoint, and Pseudomonas aeruginosa that merely lack Opr D. The researchers noted that though these bacteria are CROs, there is not as severe a clinical complication as the term connotes, unless there are other concomitant antibiotic resistances.

The study authors proposed that the terms carbapenemase-producing Enterobacterales/organisms (CPEs or CPOs) are more precise terminologies for these bacteria. However, even this they argue is still insufficient, “because different carbapenemases have differing treatment implications, particularly for new β-lactam/β-lactamase inhibitor combinations.”

The introduction of a variety of new therapies and the proliferation of diverse carbapenemases mean it is no longer acceptable to term carbapenem resistant and carbapenemase-producing bacteria as single entities. Therefore, the study authors stressed, referees and editors all have roles in ensuring clarity along with licensing and international agencies.

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“Not only in the literature, but also in routine practice it is increasingly important to detect carbapenemase production rather than carbapenem resistance and – wherever possible – to identify the enzyme family present,” concluded the researchers, adding that the terms carbapenemase-producing or non-carbapenemase-producing should be encouraged in the common vernacular.

Reference

Livermore DM, Nicolau DP, Hopkins KL, Meunier D. ‘CRE, CRO, CPE and CPO’: terminology past its ‘sell-by-date’ in an era of new antibiotics and regional carbapenemase epidemiology [published online February 6 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa122.