Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure

Nicholas Rebold, Abdalhamid M. Lagnf, Sara Alosaimy, Dana J. Holger, Paige Witucki, Andrew Mannino, Michelle Dierker, Kristen Lucas, Ashlan J. Kunz Coyne, Amer El Ghali, Kaylee E. Caniff, Michael P. Veve, Michael J. Rybak

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an “urgent” health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were $18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

Original languageEnglish
JournalMicrobiology spectrum
Issue number1
StatePublished - Jan 2023

Bibliographical note

Funding Information:
Editor Joanna B. Goldberg, Emory University School of Medicine Copyright © 2023 Rebold et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to Nicholas Rebold, Nicholas.rebold@wayne.edu, or Michael J. Rybak, m.rybak@wayne.edu. *Present address: Nicholas Rebold, Department of Clinical & Pharmacy Sciences, Howard University College of Pharmacy, Washington, DC, USA. §Present address: Sara Alosaimy, Seres Therapeutics, Cambridge, Massachusetts, USA. ^Present address: Dana J. Holger, Department of Pharmacy Practice, Nova Southeastern University College of Pharmacy, Fort Lauderdale, Florida, USA. The authors declare a conflict of interest. S.A. is an employee of Seres Therapeutics as of the completion of this manuscript. M.J.R. has received funds for research and consulting or participated in speaking bureaus for Abbvie, Contrafect, Entasis, Ferring, Melinta, Merck, Paratek Pharmaceuticals, Shionogi, Spero, Tetraphase, and T2 Bioscience and is partially supported by National Institute of Allergy and Infectious Diseases R01 AI121400 and R21 AI163726. Received 11 July 2022 Accepted 29 November 2022 Published 9 January 2023

Publisher Copyright:
© 2023 Rebold et al.


  • beta-lactams
  • carbapenem resistance
  • carbapenems
  • ceftazidime-avibactam
  • clinical failure
  • clinical therapeutics
  • CRE
  • dialysis
  • Enterobacterales
  • Enterobacteriaceae
  • Klebsiella
  • meropenem-vaborbactam
  • risk factors

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • Immunology and Microbiology (all)
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases


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