In-vitro activity of cefiderocol against multidrug-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii isolates from the UK

Background.

Cefiderocol is a parenteral siderophore cephalosporin, with a catechol-containing 3’ side chain. We evaluated its activity against MDR Gram-negative bacteria

Methods.

MICs of cefiderocol, meropenem, ceftolozane-tazobactam, cefepime, ceftazidime, aztreonam, ciprofloxacin, ceftazidime-avibactam, amikacin and colistin were determined in cation-adjusted Mueller-Hinton broth; the medium was iron depleted for cefiderocol only. The panel comprised 305 Enterobacterales, 111 P. aeruginosa and 99 A. baumannii selected for carbapenemases, ESBL production or carbapenem resistance via combinations of porin-loss with AmpC or ESBL.

Results.

The activity of cefiderocol was unrelated to Enterobacterales species. At 4mg/L cefiderocol inhibited 92.1% of all Enterobacterales, with rates of 95-100% for isolates with AmpC+porin-loss, VIM, IMP, OXA-48-like, KPC, GES, SME or IMI. Only isolates with NDM (72.1%) or ESBL+porin-loss (88.5%) had lower rates. No comparator agent inhibited >90% of isolates at EUCAST breakpoint.

Cefiderocol 4mg/L inhibited 86.5% of all P. aeruginosa, with rates of 80-100% for those with VIM, IMP, GES or VEB beta-lactamases. Lower rates were seen for those with NDM (72.7%) and PER (73.3%) enzymes. No comparator inhibited >85% of isolates at breakpoint.

Cefiderocol 4mg/L also inhibited 88.9% of A. baumannii isolates with rates >85% for those with OXA-51, -23, -24, or -58. A lower rate (80%) was seen for those with NDM carbapenemases. A concentration of 16mg/L was needed to inhibit ≥90% of A. baumannii.

Conclusions.

Cefiderocol was widely active at low concentrations against MDR Enterobacterales, P. aeruginosa and A. baumannii. MICs for isolates with NDM enzymes nonetheless were higher than for those with other carbapenemases.