Arianna Rodríguez-Coello, Michelle Outeda-García, Andrea García-Pose, Lucía Gonzalez-Pinto, Gabriela Alejandra Báez-Barroso, Paula Guijarro-Sánchez, Andrea Muras, Biel Taltavull, Pablo Fraile-Ribot, Isaac Alonso-Garcia, Antonio Oliver, Juan Carlos Vázquez-Ucha, Jorge Arca-Suárez, Germán Bou, Alejandro Beceiro
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.