Impact of a rapid molecular test for Klebsiella pneumoniae carbapenemase and ceftazidime-avibactam use on outcomes after bacteremia caused by carbapenem-resistant Enterobacterales Journal Article


Authors: Satlin, M J.; Chen, L.; Gomez-Simmonds, A.; Marino, J.; Weston, G.; Bhowmick, T.; Seo, S. K.; Sperber, S. J.; Kim, A. C.; Eilertson, B.; Derti, S.; Jenkins, S. G.; Levi, M. H.; Weinstein, M. P.; Tang, Y. W.; Hong, T.; Juretschko, S.; Hoffman, K. L.; Walsh, T. J.; Westblade, L. F.; Uhlemann, A. C.; Kreiswirth, B. N.
Article Title: 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 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 (bla KPC) 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 bla KPC 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. bla KPC 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, bla KPC 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.
Keywords: aged; sequence analysis; odds ratio; confidence intervals; drug combinations; descriptive statistics; middle age; klebsiella; treatment outcomes -- evaluation; drug resistance, microbial; nonexperimental studies; microbial culture and sensitivity tests; human; male; female; carbapenem-resistant enterobacteriaceae; bacteremia -- drug therapy; molecular diagnostic techniques -- methods; klebsiella infections -- drug therapy; bacteremia -- mortality; ceftazidime -- therapeutic use; beta-lactamases -- antagonists and inhibitors; beta-lactamases -- therapeutic use; polymyxins -- therapeutic use; carbapenems -- pharmacodynamics
Journal Title: Clinical Infectious Diseases
Volume: 75
Issue: 12
ISSN: 1058-4838
Publisher: Oxford University Press  
Date Published: 2022-12-15
Start Page: 2066
End Page: 2075
Language: English
DOI: 10.1093/cid/ciac354
PROVIDER: EBSCOhost
PROVIDER: cinahl
PUBMED: 35522019
PMCID: PMC10200298
DOI/URL:
Notes: Accession Number: 160869673 -- Entry Date: 20221228 -- Revision Date: 20221230 -- Publication Type: Article; research; tables/charts -- Journal Subset: Biomedical. -- Source: Cinahl
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  1. Susan Seo
    120 Seo
  2. Yi-Wei Tang
    188 Tang