activity of the siderophore cephalosporin, cefiderocol, against molecularly characterized, carbapenem-non-susceptible Gram-negative bacteria from Europe.

OBJECTIVES

Many carbapenem-resistant (CR) Gram-negative (GN) pathogens exhibit MDR, meaning few therapeutic options are available for CR-GN infections. Cefiderocol, a siderophore cephalosporin, has demonstrated efficacy against CR-GN bacteria. In the SIDERO-CR-2014-2016 surveillance study, European clinical isolates comprising carbapenem-non-susceptible (CarbNS) Enterobacterales and MDR non-fermenters were tested against cefiderocol and comparators.

METHODS

Cefiderocol MICs were determined using iron-depleted CAMHB, and comparators using CAMHB, per recommended CLSI methodology. Carbapenemase gene profiles were determined using PCR.

RESULTS

Isolates (870) from 23 European countries comprised CarbNS Enterobacterales (457), MDR (177) and MDR (236). The most common carbapenemases were KPC (52%), OXA-48-like (19%), VIM (14%) and NDM (8%) in Enterobacterales, VIM (41%) in and OXA-23-like (57%) and OXA-24/40-like (37%) in . Most carbapenemase-producing isolates (65%) co-carried ESBLs. Approximately half of isolates were negative for carbapenemases, compared with 10% of Enterobacterales and 3% of . A similar proportion of Enterobacterales were susceptible to cefiderocol (81.6%; 79.0% of VIM producers; 51.4% of NDM producers; based on EUCAST breakpoint values) compared with comparator antimicrobial agents, including colistin (76.4%; 93.5% of VIM producers; 78.4% of NDM producers) and ceftazidime/avibactam (76.6%; 1.6% of VIM producers; 2.7% of NDM producers). Of isolates, 98.3% were susceptible to cefiderocol (100% of VIM producers), similar to colistin (100%). Against , 94.9% had cefiderocol MIC ≤2 mg/L and 93.6% of isolates were susceptible to colistin.

CONCLUSIONS

Cefiderocol demonstrated potent activity against CarbNS and MDR GN bacteria, including non-fermenters and a wide variety of MBL- and serine-β-lactamase-producing strains.