In vitro activity of cefiderocol and comparators against isolates of Gram-negative pathogens from a range of infection sources: SIDERO‑WT‑2014-2018 studies in Spain

J Glob Antimicrob Resist. 2021 Jul 15:S2213-7165(21)00164-8. doi: 10.1016/j.jgar.2021.06.011. Online ahead of print.


OBJECTIVES: The incidence of antimicrobial resistance in Europe is rising. Cefiderocol is approved in Europe for the treatment of aerobic Gram-negative infections in adults with limited treatment options. We report the in vitro activity of cefiderocol versus comparators against Gram-negative clinical isolates from Spain.

METHODS: Minimum inhibitory concentrations were determined by broth microdilution, according to International Organization for Standardization guidelines. Cefiderocol was tested using iron-depleted cation-adjusted Mueller-Hinton broth. Susceptibility rates were based on EUCAST breakpoints; if a species-specific breakpoint was unavailable, pharmacokinetic/pharmacodynamic breakpoints were used.

RESULTS: Of 2,303 isolates (1,502 [65.2%] Enterobacterales, 801 [34.8%] non-fermenters), 2,260 (98.1%) were susceptible to cefiderocol, compared with 80.8-86.9% for comparators. By infection source, susceptibility to cefiderocol ranged from 721/741 (97.3%) in isolates from patients with nosocomial pneumonia to 349/353 (98.9%) in bloodstream infection isolates, and was greater than the susceptibility to comparators (70.7-93.6% across infection sources). Overall, 368/2,303 (16.0%) isolates were meropenem-resistant. A high proportion of meropenem-resistant A. baumannii (169/175 [96.6%]) and P. aeruginosa (48/50 [96.0%]) were cefiderocol-susceptible; similar to colistin (169/175 [96.6%] and 47/50 [94.0%], respectively) but higher than ceftazidime/avibactam (26/175 [14.9%] and 20/50 [40.0%], respectively) and ceftolozane/tazobactam (17/175 [9.7%] and 25/50 [50.0%], respectively). All Stenotrophomonas maltophilia isolates (120/120 [100%]) were cefiderocol-susceptible, including one trimethoprim/sulfamethoxazole-resistant isolate, with fewer susceptible to colistin (86/120 [71.7%]), ceftazidime/avibactam (42/120 [35.0%]) and ceftolozane/tazobactam (35/120 [29.2%]).

CONCLUSIONS: A high proportion of clinical isolates from Spain, representing a wide range of pathogens across multiple infection sources, were susceptible to cefiderocol. Cefiderocol retained activity against meropenem-resistant isolates.

PMID:34274538 | DOI:10.1016/j.jgar.2021.06.011