1887

Abstract

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 and 99 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 , 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 .

Conclusions.

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

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/content/journal/acmi/10.1099/acmi.fis2019.po0008
2020-02-28
2020-06-04
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