OBJECTIVES

This study evaluated the sustained kill and potential for resistance development of exposed to human-simulated exposure of cefiderocol over 72 h in and infection models.

METHODS

Seven isolates with cefiderocol MICs of 0.12-2 mg/L were tested. The sustained bactericidal activity compared with the initial inoculum and the resistance appearance over 72 h treatment were evaluated in both an chemostat and an murine thigh infection model under the human-simulated exposure of cefiderocol (2 g every 8 h as 3 h infusion).

RESULTS

In the model, regrowth was observed against all seven tested isolates and resistance emergence (>2 dilution MIC increase) was observed in five test isolates. Conversely, sustained killing over 72 h and no resistance emergence were observed in six of seven tested isolates . The mechanism of one resistant isolate that appeared only in the chemostat studies was a mutation in the region, which contributes to the energy transduction on the iron transporters. The resistance acquisition mechanisms of other isolates have not been identified.

CONCLUSIONS

The discrepancy in the sustained efficacy and resistance emergence between and models was observed for . Although the resistance mechanisms have not been fully identified, sustained efficacy without resistance emergence was observed for six of seven isolates. These studies reveal the bactericidal activity and the low potential for development of resistance among evaluated under human-simulated exposures.