Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia

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The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88–42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65–21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30–31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003–0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02–0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.

Original languageEnglish
Article number106250
JournalInternational journal of antimicrobial agents
Issue number2
Publication statusPublished - 2021 Feb

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)


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