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

Abstract

The incidence of antimicrobial resistance in Europe is rising. Cefiderocol is approved in Europe for treatment of aerobic Gram-negative bacterial (GNB) infections in adults with limited treatment options. We report the in vitro activity of cefiderocol versus comparators against GNB clinical isolates from Spain. MICs 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. Of 2303 isolates [1502 (65.2%) Enterobacterales and 801 (34.8%) non-fermenters], 2260 (98.1%) were susceptible to cefiderocol compared with 80.8-86.9% for comparators. By infection source, susceptibility to cefiderocol ranged from 97.3% (721/741) in isolates from patients with nosocomial pneumonia to 98.9% (349/353) in bloodstream infection isolates and was greater than susceptibility to comparators (70.7-93.6% across infection sources). Overall, 368/2303 isolates (16.0%) were meropenem-resistant. A high proportion of meropenem-resistant Acinetobacter baumannii [169/175 (96.6%)] and Pseudomonas 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 meropenem-resistant 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%)]. 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.