Fighting the spread of AmpC-hyperproducing Enterobacteriaceae: beneficial effect of replacing ceftriaxone with cefotaxime

Abstract

Objectives: Considering the hypothesis that the high biliary elimination of ceftriaxone could be responsible for the selection of Enterobacteriaceae harbouring high-level AmpC β-lactamase (HL-CASE), the use of ceftriaxone was discontinued in our hospital in 2006 and replaced with cefotaxime.

Methods: Antibiotic consumption, expressed as defined daily dose (DDD)/1000 patient-days (PD), and HL-CASE incidence, expressed as the number of patients carrying HL-CASE/1000 PD, were compared between the pre-intervention period (Period 1, 2001-05) and the post-intervention period (Period 2, 2006-12) using an interrupted time series analysis.

Results: The incidence of HL-CASE increased significantly from 0.32 to 0.69/1000 PD during Period 1 (coefficient = 0.082, P < 0.01). A significant inflection of the slope in the incidence curve occurred in Period 2 (coefficient = -0.061, P = 0.05), mainly owing to the stabilization of the HL-CASE incidence of Enterobacteriaceae harbouring chromosomally inducible cephalosporinase (Period 1, 0.27 to 0.64/1000 PD; Period 2, 0.58 to 0.61/1000 PD) and especially for Enterobacter cloacae (Period 1, 0.09 to 0.30/1000 PD; Period 2, 0.26 to 0.27/1000 PD). This deceleration was observed despite a significant increase in the slope of cefotaxime consumption over Period 2 (coefficient = 2.97, P < 0.01).

Conclusion: Despite the disadvantages of using cefotaxime compared with ceftriaxone (administration three times daily versus once a day), the ecological benefits of this substitution seem sufficiently convincing to preferentially use cefotaxime. Control of HL-CASE incidence is crucial to limiting carbapenem use and preventing the selection of carbapenemase-producing Enterobacteriaceae.

Keywords: antibiotics; bacterial resistance; cephalosporins.