In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations

• DOI: 10.1128/spectrum.03836-23
• Publication Date: 2024-04-02T14:58:50Z
• Authors: Anne Santerre Hen...; Katy Jeannot; Antonio Oliver; John D. Perry; Mathias W. Pletz; Stefania Stefani; Ian Morrissey; Christopher Longshaw; ; Birgit Willinger; David Leyssene; Christian Cattoen; Corentine Alauzet; Pierre Boyer; Véronique Dubois; Katy Jeannot; Stephane Corvec; Jean-Philippe Lav...; Thomas Guillard; Audrey Merens Gon...; Thierry Naas; Holger Rohde; Stefan Ziesing; Can Imirzalioglu; Klaus-Peter Hunfeld; Jette Jung; Sören Gatermann; Mathias Pletz; Gabriele Bianco; Anna Giammanco; Davide Carcione; Giammarco Raponi; Caterina Matinato; Enea Gino Di Dome...; Paolo Gaibani; Anna Marchese; Fabio Arena; Claudia Niccolai; Stefania Stefani; Cristina Pitart; Jose Luis Barrios; Emilia Cercenado; German Bou; Alicia Beteta Lopez; Rafael Canton; Jose Lopez Hontangas; Irene Gracia-Ahuf...; Antonio Oliver; Lorena Lopez-Cerero; Nieves Larrosa; David Wareham; John Perry; Anna Casey; Jasvir Nahl; Daniel Hughes; Michael Coyne; Michelle Lister; Marie Attwood
• Keywords: Acinetobacter baumannii; Sulbactam

ABSTRACT Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats have few approved therapeutic options. Non-‍fermenting Gram-negative isolates were collected from hospitalized inpatients 49 sites in 6 European countries between 01 January 2020 31 December underwent susceptibility testing against cefiderocol β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L), cefiderocol-susceptible analyzed by PCR, cefiderocol-resistant whole-genome sequencing to identify resistance mechanisms. Overall, 1,451 (950 P . ; 501 spp.) collected, commonly the respiratory tract (42.0% 39.3%, respectively). Cefiderocol was higher than ‍β‍-‍l‍a‍c‍t‍a‍m‍/‍β‍-‍l‍a‍c‍t‍a‍mase‍ combinations P. (98.9% vs 83.3%–91.4%), ‍aeruginosa resistant meropenem ( n = 139; 97.8% 12.2%–59.7%), (93.6%–98.1% 10.7%–71.8%), both ceftazidime-avibactam (96.7% 5.0%–‍‍45.0%) or ‍ceftolozane-tazobactam (98.4% 8.1%–54.8%), respectively. sulbactam-durlobactam susceptibilities high (92.4% 97.0%) meropenem-resistant Acineto‍bacter ‍spp. 227; 85.0% 93.8%) but lower sulbactam-durlobactam- ‍= 15; 13.3%) cefiderocol- 38; 65.8%) isolates, Among spp., most common β-‍‍lactamase genes metallo-β-lactamases [30/139; bla VIM-2 (15/139)] oxacillinases [215/227; OXA-23 (194/227)], Acquired β-lactamase identified 1/10 32/38 of pirA -like piuA mutations 10/10 37/38, Conclusion: including those recent first-line treatment non-fermenters. IMPORTANCE This first study which vitro activity non-licensed directly compared meropenem- combination-resistant isolates. A notably large number collected. Meropenem defined according MIC breakpoint for high-dose meropenem, ensuring that data reflect antibiotic would remain clinic. non-fermenters, there no apparent cross combinations, with exception sulbactam-durlobactam. These results provide insights into options infections due indicate how early parallel will allow clinicians choose effective treatment(s) all available is particularly important as current non-fermenters are limited.