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

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.

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [e-mail].

Déclaration de conflit d'intérêts

Potential conflicts of interest . M. J. S has received grant/contract support from Affinity Biosensors, Allergan (payments were made to his institution through an investigator-initiated grant [CAZ-IT-21]), BioFire Diagnostics, and Merck; served as consultant to Shionogi; and served on a Data Safety Monitoring Board for Spero Therapeutics. Y.-W. T. is an employee of Cepheid. T. J. W. has received grant support from Allergan, Amplyx, Astellas, Leadiant Biosciences, Medicines Company, Merck, Scynexis, Shionogi, T2 Biosystems, Tetraphase, and Viosera and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Karyopharm, Leadiant Biosciences, Medicines Company, Merck, Methylgene, Partner Therapeutics, Pfizer, Scynexis, Shionogi, and T2 Biosystems. L. F. W. has received grant support from Accelerate Diagnostics, BioFire Diagnostics, and Roche Molecular Systems and has served as consultant to Roche Molecular Systems, Shionogi, and Talis Biomedical. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.