Distinctive Features of Ertapenem-Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study

Background: Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem "mono-resistant") represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods: We analyzed surveillance data from 9 CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem "mono-resistant"cases to "other"CRE cases (resistant to ≥1 carbapenem other than ertapenem) and analyzed risk factors for mortality. Results: Of 2009 cases, 1249 (62.2%) were ertapenem-mono-resistant and 760 (37.8%) were other CRE. Ertapenem-mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs 19.5%; P < .0001) and female (67.9% vs 59.0%; P < .0001). Ertapenem-mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs 15.4%; P < .0001) but less likely to be isolated from a normally sterile site (7.1% vs 11.7%; P < .01) or to have a carbapenemase gene (2.4% vs 47.4%; P < .0001). Ertapenem-mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio, 1.93; 95% CI, 1.30-2.86). Conclusions: Ertapenem-mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available.