In vitro activity of the novel siderophore cephalosporin, cefiderocol, in Gram-negative pathogens in Europe by site of infection

Objectives: We assessed the activity of the novel siderophore cephalosporin, cefiderocol and selected other antibacterial agents against Gram-negative bacterial isolates in Europe. Methods: Isolates were obtained between 2013 and 2018 from European countries participating in the SIDERO-WT and SIDERO-Proteeae multinational surveillance studies. Isolates were categorised by infection site, focusing on bloodstream infections, hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections and complicated urinary tract infections. Cefiderocol activity was compared with ceftazidime-avibactam, ceftolozane-tazobactam, colistin and meropenem using standard susceptibility testing methods. European Committee on Anti-microbial Susceptibility Testing (EUCAST) breakpoints were used to interpret susceptibility data. Results: Isolates (n = 20 911) were collected from 145 sites in 24 countries in Europe, the highest proportion (34%) being from patients with HABP/VABP. Enterobacterales (66.6% of isolates) were more frequent than glucose non-fermenting species (33.4%) overall, with some differences between infection sites. Across all infection sites, the MIC50/MIC(90)( )for cefiderocol was <= 0.5/<= 2 mg/L for Enterobacter spp., <= 0.25/<2 mg/L for Klebsiella spp., 0.12/2 mg/L for Acinetobacter spp., <= 0.25/1 mg/L for Pseudomonas aeruginosa and <= 0.12/<= 0.5 mg/L for Stenotrophomonas maltophilia. Across all infection sites, cefiderocol MICs were <= 2 mg/L for >= 96% of Enterobacter spp., >= 95% of Klebsiella spp., >= 90% of Acinetobacter spp. and >= 99% of Pseudomonas aeruginosa and Stenotrophomonas maltophilia isolates. Cefiderocol maintained high activity in carbapenem-resistant isolates, and the difference in activity between carbapenem-resistant (percentage susceptibility at EUCAST breakpoint: E. coli 77.8%, Klebsiella spp. 69.2%, Pseudomonas aeruginosa 97.5%, Acinetobacter spp. 90.7%, Stenotrophomonas maltophilia 99.6%) and carbapenem-susceptible (percentage susceptibility at EUCAST breakpoint: E. coli 99.4%, Klebsiella spp. 98.0%, Pseudomonas aeruginosa 99.7%, Acinetobacter spp. 94.9%) isolates was lower for cefiderocol than other agents. Conclusions: Cefiderocol had excellent activity against all Gram-negative species, independent of key infection site and carbapenem MIC. Cefiderocol is a useful addition to the therapeutic options available for these difficult-to-treat infections. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.