In vivo efficacy of cefiderocol against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa carrying the AmpC E219K substitution.

Chromosomal AmpC variants selected during ceftolozane/tazobactam or ceftazidime/avibactam therapy may affect cefiderocol activity. We evaluated the impact of the E219K substitution on cefiderocol efficacy using isogenic Pseudomonas aeruginosa pairs in a murine bacteremia model. Cefiderocol achieved greater bacterial reductions in parental isolates than in E219K derivatives, despite susceptible MICs. Cefiderocol failed to achieve stasis against a cefiderocol-resistant isolate. E219K impaired cefiderocol efficacy in vivo, supporting close monitoring of cefiderocol activity against isolates carrying this variant.