In vivo study shows the E219K substitution in Pseudomonas aeruginosa PDC ß-lactamase reduces cefiderocol efficacy despite susceptible MICs, highlighting the need for clinical monitoring.
Chromosomal PDC ß-lactamase modifications emerging during ceftolozane/tazobactam or ceftazidime/avibactam therapy may affect cefiderocol activity. We evaluated the E219K substitution using isogenic Pseudomonas aeruginosa pairs in a murine bacteraemia model. Cefiderocol achieved greater bacterial reductions in pre-treatment isolates (1.55-2.94 log10 CFU/g) than in E219K mutants (0.78-1.39 log10 CFU/g; P<0.01), despite MICs within the susceptible range. A cefiderocol-resistant control isolate failed to reach stasis. E219K reduces cefiderocol efficacy in vivo, supporting careful monitoring and consideration of alternative therapies.
Chromosomal PDC ß-lactamase modifications emerging during ceftolozane/tazobactam or ceftazidime/avibactam therapy may affect cefiderocol activity. We evaluated the E219K substitution using isogenic Pseudomonas aeruginosa pairs in a murine bacteraemia model. Cefiderocol achieved greater bacterial reductions in pre-treatment isolates (1.55-2.94 log10 CFU/g) than in E219K mutants (0.78-1.39 log10 CFU/g; P<0.01), despite MICs within the susceptible range. A cefiderocol-resistant control isolate failed to reach stasis. E219K reduces cefiderocol efficacy in vivo, supporting careful monitoring and consideration of alternative therapies.
Institut d'Investigacio Sanitaria de Palma