In vitro and in vivo efficacy of cefiderocol plus tigecycline, colistin, or meropenem against carbapenem-resistant Acinetobacter baumannii.

ABSTRACT

We investigated activities of cefiderocol combination therapy against carbapenem-resistant Acinetobacter baumannii (CR-AB). A total of 123 clinical isolates of CR-AB, including 44 cefiderocol-resistant isolates were tested. Cefiderocol functioned synergistically with tigecycline in most cefiderocol-susceptible isolates (84.8%, 67/79), but not with colistin or meropenem by checkerboard method. Cefiderocol functioned synergistically with tigecycline, colistin, and meropenem in 90.9% (40/44), 47.7% (21/44), and 79.5% (35/44) cefiderocol-resistant isolates, respectively. The time-kill assay and the in vivo Galleria mellonella model confirmed these observations. In summary, cefiderocol combined with tigecycline showed synergistic effects against both cefiderocol-susceptible and -resistant CR-AB, suggesting a potentially valuable combination regimen.