Activity of Cefiderocol Against Meropenem-Nonsusceptible Gram-Negative Bacilli with Defined β-Lactamase Carriage: SIDERO-WT Surveillance Studies, 2014-2019.

We examined the susceptibility of meropenem-nonsusceptible Enterobacterales, , and complex isolates from five consecutive annual SIDERO-WT surveillance studies (2014-2019) to cefiderocol and comparator agents in the context of their carbapenemase carriage. 1,003 Enterobacterales, 1,758 , and 2,809 complex isolates from North America and Europe that were meropenem nonsusceptible (CLSI M100, 2022) were molecularly characterized for β-lactamase content by PCR followed by Sanger sequencing or by whole genome sequencing. Among Enterobacterales, 91.5% of metallo-β-lactamase (MBL)-producing, 98.4% of KPC-producing, 97.3% of OXA-48 group-producing, and 98.7% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among , 100% of MBL-producing, 100% of GES carbapenemase-producing, and 99.8% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among complex, 60.0% of MBL-producing, 95.6% of OXA-23 group-producing, 89.5% of OXA-24 group-producing, 100% of OXA-58 group-producing, and 95.5% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Cefiderocol was inactive against complex isolates carrying a PER or VEB β-lactamase ( = 103; 15.5% susceptible). Ceftazidime-avibactam and ceftolozane-tazobactam were inactive against MBL-carrying and complex isolates; ceftolozane-tazobactam was also inactive against serine carbapenemase-carrying Enterobacterales and . In summary, cefiderocol was highly active against Gram-negative isolates carrying MBLs and serine carbapenemases, as well as carbapenemase-negative, meropenem-nonsusceptible isolates.