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.
“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.
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.