In vitro activity of cefiderocol in Pseudomonas aeruginosa isolates from people with cystic fibrosis recovered during three multicentre studies in Spain.
J Antimicrob Chemother
; 79(6): 1432-1440, 2024 Jun 03.
Article
in En
| MEDLINE
| ID: mdl-38708553
ABSTRACT
OBJECTIVES:
Despite the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Pseudomonas aeruginosa is still a major pathogen in people with cystic fibrosis (pwCF). We determine the activity of cefiderocol and comparators in a collection of 154 P. aeruginosa isolates recovered from pwCF during three multicentre studies performed in 17 Spanish hospitals in 2013, 2017 and 2021.METHODS:
ISO broth microdilution was performed and MICs were interpreted with CLSI and EUCAST criteria. Mutation frequency and WGS were also performed.RESULTS:
Overall, 21.4% were MDR, 20.8% XDR and 1.3% pandrug-resistant (PDR). Up to 17% of the isolates showed a hypermutator phenotype. Cefiderocol demonstrated excellent activity; only 13 isolates (8.4%) were cefiderocol resistant by EUCAST (none using CLSI). A high proportion of the isolates resistant to ceftolozane/tazobactam (71.4%), meropenem/vaborbactam (70.0%), imipenem/relebactam (68.0%) and ceftazidime/avibactam (55.6%) were susceptible to cefiderocol. Nine out of 13 cefiderocol-resistant isolates were hypermutators (Pâ<â0.001). Eighty-three STs were detected, with ST98 being the most frequent. Only one isolate belonging to the ST175 high-risk clone carried blaVIM-2. Exclusive mutations affecting genes involved in membrane permeability, AmpC overexpression (L320P-AmpC) and efflux pump up-regulation were found in cefiderocol-resistant isolates (MICâ=â4-8â mg/L). Cefiderocol resistance could also be associated with mutations in genes related to iron uptake (tonB-dependent receptors and pyochelin/pyoverdine biosynthesis).CONCLUSIONS:
Our results position cefiderocol as a therapeutic option in pwCF infected with P. aeruginosa resistant to most recent ß-lactam/ß-lactamase inhibitor combinations.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pseudomonas aeruginosa
/
Pseudomonas Infections
/
Microbial Sensitivity Tests
/
Cephalosporins
/
Cystic Fibrosis
/
Cefiderocol
/
Anti-Bacterial Agents
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
J Antimicrob Chemother
Year:
2024
Document type:
Article
Affiliation country:
Spain