Abstract
BackgroundCefiderocol, 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.MethodsWe 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.ResultsThere 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.ConclusionsAll 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.
Highlights
Escherichia coli is one of the leading causes of community onset and nosocomial bloodstream infection [1, 2]
This study aimed to determine the potential for ceftolozane-tazobactam, ceftazidime-avibactam, IV fosfomycin, cefiderocol and plazomicin to be used as an alternative to carbapenem-based therapy for patients with bloodstream infection caused by E. coli that are non-susceptible to ceftriaxone by analysis of a real-life patient cohort
Susceptibility testing for ceftolozane/tazobactam, ceftazidime/avibactam (Liofilchem) and plazomicin (Liofilchem) were performed by minimum inhibitory concentration (MIC) strips according to manufacturer instructions [16,17,18]
Summary
Escherichia coli is one of the leading causes of community onset and nosocomial bloodstream infection [1, 2]. E. coli harbouring extended-spectrum beta-lactamases (ESBL) or AmpC beta-lactamases are resistant to oxyiminocephalosporins such as ceftriaxone and have emerged. While Australia has low rates of resistance by global standards, the proportion of E. coli harbouring ESBLs have increased between 2013 and 2017 to more than 10% of isolates [2]. Carbapenems are the current treatment of choice for ESBL or AmpC producing E. coli bloodstream infections. Rising carbapenem use has been associated with the emergence of carbapenem resistant infections [5]. Amongst other infection control measures, carbapenem sparing strategies offer significant appeal in reducing the emergence of carbapenem resistance. 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. Available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications
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