In Vitro Susceptibility of Gram-Negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies, 2014 to 2019

Abstract

We report in vitro susceptibility data from five consecutive annual SIDERO-WT surveillance studies (2014 to 2019) for cefiderocol and comparators tested against Gram-negative clinical isolates from North America and Europe. CLSI broth microdilution was used to determine MICs for Enterobacterales (n = 31,896), Pseudomonas aeruginosa (n = 7,700), Acinetobacter baumannii complex (n = 5,225), Stenotrophomonas maltophilia (n = 2,030), and Burkholderia cepacia complex (n = 425). MICs were interpreted by CLSI-approved clinical breakpoints (February 2021). Cefiderocol inhibited 99.8, 96.7, 91.6, and 97.7% of all Enterobacterales, meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/mL (susceptible breakpoint). Cefiderocol inhibited 99.9, 99.8, 100, and 99.8% of all P. aeruginosa, meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/mL (susceptible breakpoint). Cefiderocol inhibited 96.0% of all A. baumannii complex isolates and 94.2% of meropenem-nonsusceptible isolates at ≤4 μg/mL (susceptible breakpoint) and 98.6% of S. maltophilia isolates at ≤1 μg/mL (susceptible breakpoint). B. cepacia complex isolates were tested with a MIC₅₀ of ≤0.03 μg/mL and MIC₉₀ of 0.5 μg/mL. Annual cefiderocol percent susceptible rates for Enterobacterales (North America range, 99.6 to 100%/year; Europe range, 99.3 to 99.9%/year) and P. aeruginosa (North America range, 99.8 to 100%; Europe range, 99.9 to 100%) were unchanged from 2014 to 2019. Annual percent susceptible rates for A. baumannii complex demonstrated sporadic, nondirectional differences (North America range, 97.5 to 100%; Europe range, 90.4 to 97.5%); the wider range for Europe (∼7%) was due to isolates from Russia. Annual percent susceptible rates for S. maltophilia showed minor, nondirectional differences (North America range, 96.4 to 100%; Europe range, 95.6 to 100%). We conclude that clinical isolates of Enterobacterales (99.8% susceptible), P. aeruginosa (99.9%), A. baumannii (96.0%), and S. maltophilia (98.6%) collected in North America and Europe from 2014 to 2019 were highly susceptible to cefiderocol.

Keywords: Acinetobacter baumannii; CRE; Gram-negative bacilli; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; carbapenem-resistant Enterobacterales; cefiderocol.

FIG 1

Cefiderocol MIC distributions for combined North America and Europe isolates of (A) meropenem-susceptible (MIC, ≤1 μg/mL) (white bars; n = 30,875) and meropenem-nonsusceptible (MIC, ≥2 μg/mL) (black bars; n = 1,021) Enterobacterales, (B) meropenem-susceptible (MIC, ≤2 μg/mL) (white bars; n = 5,941) and meropenem-nonsusceptible (MIC, ≥4 μg/mL) (black bars; n = 1,759) P. aeruginosa, and (C) meropenem-susceptible (MIC, ≤2 μg/mL) (white bars; n = 2,415) and meropenem-nonsusceptible (MIC, ≥4 μg/mL) (black bars; n = 2,810) A. baumannii complex. MIC breakpoints for cefiderocol tested against Enterobacterales are as follows: CLSI and FDA, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant, >2 μg/mL. MIC breakpoints for cefiderocol tested against P. aeruginosa are as follows: CLSI, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; FDA, susceptible, ≤1 μg/mL, intermediate, 2 μg/mL, and resistant, ≥4 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant, >2 μg/mL. MIC breakpoints for cefiderocol tested against A. baumannii complex are as follows: CLSI, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant >2 μg/mL. FDA does not publish MIC breakpoints for cefiderocol tested against isolates of Acinetobacter spp.

FIG 2

Cefiderocol MIC distributions for combined North America and Europe isolates of (A) ceftazidime-avibactam-susceptible (MIC, ≤8 μg/mL) (white bars; n = 31,633) and ceftazidime-avibactam-resistant (MIC, ≥16 μg/mL) (black bars; n = 263) Enterobacterales and (B) ceftazidime-avibactam-susceptible (MIC ≤8 μg/mL) (white bars; n = 7,223) and ceftazidime-avibactam-resistant (MIC, ≥16 μg/mL) (black bars; n = 477) P. aeruginosa. MIC breakpoints for cefiderocol tested against Enterobacterales are as follows: CLSI and FDA, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant >2 μg/mL. MIC breakpoints for cefiderocol tested against P. aeruginosa are as follows: CLSI, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; FDA, susceptible, ≤1 μg/mL, intermediate, 2 μg/mL, and resistant, ≥4 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant, >2 μg/mL.

FIG 3

Cefiderocol MIC distributions for combined North America and Europe isolates of (A) ceftolozane-tazobactam-susceptible (MIC, ≤2 μg/mL) (white bars; n = 29,238) and ceftolozane-tazobactam-resistant (MIC, ≥4 μg/mL) (black bars; n = 2,950) Enterobacterales and (B) ceftolozane-tazobactam-susceptible (MIC, ≤4 μg/mL) (white bars; n = 7,237) and ceftolozane-tazobactam-resistant (MIC, ≥8 μg/mL) (black bars; n = 463) P. aeruginosa. MIC breakpoints for cefiderocol tested against Enterobacterales are as follows: CLSI and FDA, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant, >2 μg/mL. MIC breakpoints for cefiderocol tested against P. aeruginosa are as follows: CLSI, susceptible, ≤4 μg/mL, intermediate, 8 μg/mL, and resistant, ≥16 μg/mL; FDA, susceptible, ≤1 μg/mL, intermediate, 2 μg/mL, and resistant, ≥4 μg/mL; EUCAST, susceptible, ≤2 μg/mL, and resistant, >2 μg/mL.