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

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 2016-2018 at eight 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 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 = 0.009) compared to other patients (n = 86) and decreased 14-day (16% vs. 37%; P = 0.007) and 30-day (24% vs. 47%; P = 0.007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio 0.37; 95% confidence interval: 0.16-0.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = 0.08). 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.

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure

“…Chronic dialysis may also be an area for further investigation with antibiotic dosing to improve outcomes among CRE infections due to its especially high association with clinical failure. Rapid diagnostics and aggressive antibiotic use early in disease may be warranted for these high-risk characteristics among CRE infections, with recent research in CRE bacteremia showing positive outcomes ( 25 ). Research should continue on carbapenem-resistant Enterobacterales infections in large, randomized cohorts and case-control studies to further identify best practices to promote treatment success.…”

Mortality-Related Risk Factors and Novel Antimicrobial Regimens for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review

“…In total, 28 eligible studies were included. 11,13,21,26,31,32,36,[38][39][40][41]43,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] The characteristics of the studies are presented in Table 4. Only studies that reported mortality as a treatment outcome were presented.…”

Early and Appropriate Use of Ceftazidime-Avibactam in the Management of Multidrug-Resistant Gram-Negative Bacterial Infections in the Indian Scenario

“…Overall, this may lead to a decrease in mortality, shorter hospital stays, and a reduction in hospitalization costs [44][45][46][47]. Rapid diagnostics is associated with early intervention with effective antimicrobial therapy which may lead to improved clinical outcomes and decreased mortality [48].…”