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

• Published in: Clinical infectious diseases 2022-12, Vol.75 (12), p.2066-2075
• Main Authors: Satlin, Michael J, Chen, Liang, Gomez-Simmonds, Angela, Marino, Jamie, Weston, Gregory, Bhowmick, Tanaya, Seo, Susan K, Sperber, Steven J, Kim, Angela C, Eilertson, Brandon, Derti, Sierra, Jenkins, Stephen G, Levi, Michael H, Weinstein, Melvin P, Tang, Yi-Wei, Hong, Tao, Juretschko, Stefan, Hoffman, Katherine L, Walsh, Thomas J, Westblade, Lars F, Uhlemann, Anne-Catrin, Kreiswirth, Barry N
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - therapeutic use; Azabicyclo Compounds - therapeutic use; Bacteremia - drug therapy; Bacterial Proteins - genetics; beta-Lactamase Inhibitors - therapeutic use; beta-Lactamases - genetics; Carbapenems - pharmacology; Ceftazidime - therapeutic use; Drug Combinations; Humans; Klebsiella Infections - drug therapy; Klebsiella pneumoniae; Major; Microbial Sensitivity Tests
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciac354

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. In this multicenter observational study of bacteremias caused by carbapenem-resistant Enterobacterales, use of a molecular assay that detects the Klebsiella pneumoniae carbapenemase gene directly from positive blood culture broths was associated with shorter delays in appropriate therapy and decreased mortality.