Impact of a Rapid Molecular Test for Klebsiella pneumoniae Carbapenemase and Ceftazidime-Avibactam Use on Outcomes After Bacteremia Caused by Carbapenem-Resistant Enterobacterales

Michael J. Satlin, Liang Chen, Angela Gomez-Simmonds, Jamie Marino, Gregory Weston, Tanaya Bhowmick, Susan K. Seo, Steven J. Sperber, Angela C. Kim, Brandon Eilertson, Sierra Derti, Stephen G. Jenkins, Michael H. Levi, Melvin P. Weinstein, Yi Wei Tang, Tao Hong, Stefan Juretschko, Katherine L. Hoffman, Thomas J. Walsh, Lars F. WestbladeAnne Catrin Uhlemann, Barry N. Kreiswirth

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

BACKGROUND: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new β-lactam/β-lactamase inhibitors may improve outcomes. METHODS: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. RESULTS: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). CONCLUSIONS: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.

Original languageEnglish (US)
Pages (from-to)2066-2075
Number of pages10
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume75
Issue number12
DOIs
StatePublished - Dec 19 2022

Keywords

  • Klebsiella pneumoniae carbapenemase
  • carbapenem-resistant Enterobacterales
  • ceftazidime-avibactam
  • rapid diagnostics

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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