Abstract
Cefiderocol is a parenteral siderophore cephalosporin, with a
catechol-containing 3′ substituent. We evaluated its MICs against
gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The
panel comprised 305 Enterobacterales, 111 P. aeruginosa and 99 A. baumannii,
all selected for carbapenem resistance and multi-resistance to other
agents. At 2 and 4 μg/ml cefiderocol inhibited 78.7% and 92.1%
respectively of all Enterobacterales tested, with rates of 80-100% for
isolates with all modes of carbapenem resistance except NDM enzymes
(41.0% inhibited at 2 μg/ml, 72.1% at 4 μg/ml) or combinations of ESBL
and porin-loss (61.5% inhibited at 2 μg/ml, 88.5% at 4 μg/ml).
Cefiderocol also inhibited 81.1% and 86.5% of all P. aeruginosa
at 2 and 4 μg/ml respectively, with rates of 80-100% for isolates with
VIM, IMP, GES or VEB β-lactamases and slightly lower rates for those
with NDM (45.5% at 2 μg/ml and 72.7% at 4 μg/ml) and PER (66.7% at 2
μg/ml and 73.3% at 4 μg/ml) enzymes; 63.3% of P. aeruginosa were inhibited at the FDA's 1 μg/ml breakpoint. Lastly, cefiderocol 2 and 4 μg/ml inhibited 80.8% and 88.9% of the A. baumannii
isolates respectively, with rates >85% for isolates with
OXA-51-like, -23, -24, or -58 enzymes and 50% at 2 μg/ml and 80% at 4
μg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam
weakly potentiated cefiderocol against Enterobacterales with MBLs and
serine carbapenemase respectively, indicating incomplete β-lactamase
stability.
Original language | English |
---|---|
Article number | e01582-20 |
Journal | Antimicrobial Agents and Chemotherapy |
Volume | 64 |
Issue number | 12 |
Early online date | 21 Sept 2020 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- Acinetobacter baumannii
- Antimicrobial activity
- Antimicrobial resistance
- Carbapenamase
- Cefiderocol
- Enterobacterales
- Enterobacteriaceae
- Multidrug resistance
- NDM
- Pseudomonas aeruginosa
Profiles
-
David Livermore
- Norwich Medical School - Professorial Fellow
- Epidemiology and Public Health - Member
Person: Honorary, Research Group Member