Clinical syndromes and treatment location predict utility of carbapenem sparing therapies in ceftriaxone-non-susceptible Escherichia coli bloodstream infection

Ouli Xie*, Kathryn Cisera, Lucy Taylor, Carly Hughes, Benjamin Rogers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications. Methods: We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent. Results: There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam. Conclusions: All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.

Original languageEnglish
Article number57
JournalAnnals of Clinical Microbiology and Antimicrobials
Volume19
Issue number1
DOIs
Publication statusPublished - Dec 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Merck Sharp & Dohme (MSD) Australia (Grant Number IIS 57091) who provided funding for a portion of the laboratory work in this study. MSD Australia was not involved in the study design, analysis, writing, or decision to submit for publication. In-kind support for consumables was also received; Ceftolozane/Tazobactam Etests (MSD Australia) and Cefiderocol discs (Shionogi, via a third party).

Publisher Copyright:
© 2020, The Author(s).

Keywords

  • Bacteremia
  • Ceftriaxone
  • Drug resistance
  • Escherichia coli infections
  • Meropenem

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