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

Abstract

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.