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. 2021 Dec 29;9(1):ofab643.
doi: 10.1093/ofid/ofab643. eCollection 2022 Jan.

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

Max W Adelman  1   2 , Chris W Bower  2   3   4 , Julian E Grass  5 , Uzma A Ansari  5 , Elizabeth A Soda  5 , Isaac See  5 , Joseph D Lutgring  5 , Jesse T Jacob  1   2   6   7
Affiliations

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

Max W Adelman et al. Open Forum Infect Dis. .

Abstract

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.

Keywords: antibiotic resistance; carbapenem-resistant Enterobacterales; carbapenemase; ertapenem.

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Figures

Figure 1.
Figure 1.
Flow diagram of CRE cases included in analysis, 2016–2017. Ertapenem-mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Abbreviations: CRE, carbapenem-resistant Enterobacterales; MIC, minimum inhibitory concentration.
Figure 2.
Figure 2.
Proportion of ertapenem-mono-resistant CRE vs other CRE isolates with specific carbapenemase genes. Ertapenem-mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Testing for carbapenemase genes was performed by real-time polymerase chain reaction at the CDC. Abbreviations: CDC, Centers for Disease Control and Prevention; CRE, carbapenem-resistant Enterobacterales.
Figure 3.
Figure 3.
Proportion of ertapenem-mono-resistant CRE vs other CRE isolates susceptible to selected antibiotics. Ertapenem-mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Classification of an isolate as susceptible, intermediate, or resistant was determined for minimum inhibitory concentrations of selected antibiotics according to CLSI criteria based on testing performed at clinical laboratories [18]. If an isolate was not tested against a certain antibiotic, it was not included in this figure. ∗P < .05. Abbreviation: CRE, carbapenem-resistant Enterobacterales.
Figure 4.
Figure 4.
Survival analysis comparing patients with CRE that are ertapenem-mono-resistant to other CRE (ie, resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (ie, sterile site vs urine) (B); and comparing patients with CRE that have carbapenemase genes, either total (C) or stratified by isolate site (D). Presence of carbapenemase gene and sterile isolate site was associated with differences in survival, but ertapenem-mono-resistant CRE were not associated with a mortality difference compared with other CRE. Abbreviation: CRE, carbapenem-resistant Enterobacterales.
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