The Journal of infectious diseases · 2026
Genomic and Clinical Features Associated With Reduced Susceptibility to Cefiderocol and Cross-Resistance to β-Lactam/β-Lactamase Inhibitors in a Global Cohort of Pseudomonas aeruginosa.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Egge Stephanie L, Kang Donghoon, Pouya Nazanin, Thornton Philip C, Flores Erika, Clarke Karim, Adelman Max W, Rosenbaum Cornelius L, Baptista Rodrigo P, Arias Cesar A, Tam Vincent H, Satlin Michael J, Miller William R
Аннотация
BACKGROUND: Cefiderocol retains high rates of activity against carbapenem-resistant P. aeruginosa (CRPA) and is being introduced as a last resort antibiotic in developing countries. This study assessed the clinical and genotypic characteristics associated with decreased cefiderocol susceptibility among a global collection of CRPA isolates.
METHODS: Clinical isolates (n = 186) selected from 972 patients enrolled from 10 countries as part of the Prospective Observational Pseudomonas (POP) study were characterized by whole-genome sequencing, cefiderocol broth microdilution, and population analysis profile. We compared clinical and genomic characteristics between susceptible isolates and those with reduced cefiderocol susceptibility (defined as heteroresistant by population analysis, or intermediate or resistant using current breakpoints). A hollow fiber infection model was used to evaluate the emergence of resistance under human serum simulated cefiderocol exposures.
RESULTS: Of the 186 isolates, 11 (5.9%) were cefiderocol nonsusceptible and 28 (15.1%) were heteroresistant using CLSI breakpoints. With EUCAST breakpoints, 20 (10.8%) were cefiderocol resistant and 20 (10.8%) were heteroresistant. Reduced susceptibility isolates were present across all geographic regions and harbored changes in PirRS-regulated siderophore receptors, AmpC β-lactamase mutations associated with decreased ceftolozane/tazobactam susceptibility, cpxS mutations, and the β-lactamases blaNDM and blaVEB. Resistance to ceftolozane/tazobactam and ceftazidime/avibactam were independently associated with reduced cefiderocol susceptibility. Cefiderocol resistance emerged in a heteroresistant, but not susceptible isolate at human simulated exposures.
CONCLUSIONS: Decreased cefiderocol susceptibility is present worldwide and is not restricted to a clonal high-risk lineage. This raises concerns about the use of cefiderocol as a salvage regimen in patients with multidrug-resistant P. aeruginosa infection.
METHODS: Clinical isolates (n = 186) selected from 972 patients enrolled from 10 countries as part of the Prospective Observational Pseudomonas (POP) study were characterized by whole-genome sequencing, cefiderocol broth microdilution, and population analysis profile. We compared clinical and genomic characteristics between susceptible isolates and those with reduced cefiderocol susceptibility (defined as heteroresistant by population analysis, or intermediate or resistant using current breakpoints). A hollow fiber infection model was used to evaluate the emergence of resistance under human serum simulated cefiderocol exposures.
RESULTS: Of the 186 isolates, 11 (5.9%) were cefiderocol nonsusceptible and 28 (15.1%) were heteroresistant using CLSI breakpoints. With EUCAST breakpoints, 20 (10.8%) were cefiderocol resistant and 20 (10.8%) were heteroresistant. Reduced susceptibility isolates were present across all geographic regions and harbored changes in PirRS-regulated siderophore receptors, AmpC β-lactamase mutations associated with decreased ceftolozane/tazobactam susceptibility, cpxS mutations, and the β-lactamases blaNDM and blaVEB. Resistance to ceftolozane/tazobactam and ceftazidime/avibactam were independently associated with reduced cefiderocol susceptibility. Cefiderocol resistance emerged in a heteroresistant, but not susceptible isolate at human simulated exposures.
CONCLUSIONS: Decreased cefiderocol susceptibility is present worldwide and is not restricted to a clonal high-risk lineage. This raises concerns about the use of cefiderocol as a salvage regimen in patients with multidrug-resistant P. aeruginosa infection.
Предметные рубрики MeSH
AdultAgedFemaleHumansMaleMiddle AgedAnti-Bacterial Agentsbeta-Lactamase InhibitorsCefiderocolCeftazidimeCephalosporinsDrug Resistance, Multiple, BacterialMicrobial Sensitivity TestsProspective StudiesPseudomonas aeruginosaPseudomonas InfectionsThird Generation CephalosporinsWhole Genome SequencingDrug CombinationsAzabicyclo Compounds