In vitro activity of cefiderocol and comparators against Gram-negative bacterial isolates from a series of surveillance studies in England: 2014-2018

Vanya Gant; Abid Hussain; Malcolm Bain; Christopher Longshaw; Anne Santerre Henriksen

doi:10.1016/j.jgar.2021.07.014

In vitro activity of cefiderocol and comparators against Gram-negative bacterial isolates from a series of surveillance studies in England: 2014-2018

J Glob Antimicrob Resist. 2021 Dec:27:1-11. doi: 10.1016/j.jgar.2021.07.014. Epub 2021 Jul 27.

Authors

Vanya Gant¹, Abid Hussain², Malcolm Bain³, Christopher Longshaw³, Anne Santerre Henriksen⁴

Affiliations

¹ University College London Hospitals NHS Foundation Trust, London, UK. Electronic address: vanyagant@nhs.net.
² University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. Electronic address: abid.hussain3@uhb.nhs.uk.
³ Infectious Diseases, Shionogi B.V., London, UK.
⁴ Maxel Consulting ApS, Jyllinge, Denmark; contractor for Shionogi B.V., London, UK.

PMID: 34329792
DOI: 10.1016/j.jgar.2021.07.014

Abstract

Objectives: The prevalence of Gram-negative bacteria (GNB) demonstrating extensive, multiple antimicrobial resistance is increasing in England, leaving few treatment choices. Cefiderocol is a novel siderophore cephalosporin approved in Europe for the treatment of aerobic GNB infections in adults with limited treatment options. We report pooled data for a clinical isolate set collected in England between 2014-2018.

Methods: MICs were determined by broth microdilution according to International Organization for Standardization guidelines. Cefiderocol susceptibility was tested using iron-depleted cation-adjusted Muller-Hinton broth. Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/pharmacodynamic breakpoints were used.

Results: Of 1886 isolates from England [74.1% Enterobacterales (18.7% Escherichia coli, 17.2% Klebsiella pneumoniae), 25.9% non-fermenters (18.4% Pseudomonas aeruginosa, 3.7% Acinetobacter baumannii)], 98.7% were cefiderocol-susceptible. Cefiderocol susceptibility in Enterobacterales (99.0%) was significantly (P < 0.01) greater than ceftolozane/tazobactam (94.3%), but similar to meropenem (99.3%) and ceftazidime/avibactam (99.4%). Overall, cefiderocol susceptibility (98.0%) in non-fermenters was significantly (P < 0.01) higher than comparators (range, 84.5-92.4%). Susceptibility to cefiderocol was 98.3-99.6% by infection source and was significantly (P < 0.01) greater than comparators for isolates from patients with nosocomial pneumonia (cefiderocol, 98.3%; comparators range, 79.8-93.8%). Excluding intrinsically meropenem-resistant Stenotrophomonas maltophilia, 47/1846 isolates (2.5%) were meropenem-resistant. A high proportion of meropenem-resistant P. aeruginosa were susceptible to cefiderocol (95.0%). All S. maltophilia isolates (40/40) were cefiderocol-susceptible.

Conclusion: A substantial proportion of clinical isolates from England, representing a wide range of pathogens across multiple infection sources, was cefiderocol-susceptible. Cefiderocol retained activity against meropenem-resistant strains.

Keywords: Carbapenem resistance; Epidemiology; Gram-negative; Resistance; Surveillance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents* / pharmacology
Cefiderocol
Cephalosporins* / pharmacology
Gram-Negative Bacteria
Humans
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Cephalosporins