4.6 Article

Assessment of In Vitro Cefiderocol Susceptibility and Comparators against an Epidemiologically Diverse Collection of Acinetobacter baumannii Clinical Isolates

Journal

ANTIBIOTICS-BASEL
Volume 11, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/antibiotics11020187

Keywords

Acinetobacter baumannii; antibiotic resistance; carbapenem; MDR; trojan horse; cefiderocol; siderophore; epidemiology

Funding

  1. Plan Nacional de I+D+i 2013-2016, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0010]
  2. 2017 call for Strategic Action on Health [PI17/01932, PI17/01468]
  3. European Development Regional Fund A way to achieve Europe
  4. operative program Intelligent Growth 2014-2020
  5. Departament d'Universitats, Recerca i Societat de la Informacio, of the Generalitat de Catalunya [2017 SGR 0809]
  6. COMBACTECARE project [115620]
  7. Department of Health, Generalitat de Catalunya [SLT002/16/00349]
  8. Spanish Ministry of Science, Innovation and Universities through the Centro de Excelencia Severo Ochoa 2019-2023 Program [CEX2018-000806-S]
  9. Generalitat de Catalunya through the CERCA Program
  10. Shionogi B.V.

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This study investigated the in vitro antimicrobial activity of cefiderocol and other antibiotics against a diverse collection of Acinetobacter baumannii clinical isolates, revealing cefiderocol and colistin as the most active agents. Notably, cefiderocol demonstrated superior efficacy against multidrug-resistant and carbapenem-resistant A. baumannii isolates, suggesting it as a promising alternative treatment option for infections caused by these strains.
Cefiderocol is a catechol-substituted siderophore cephalosporin combining rapid penetration into the periplasmic space with increased stability against beta-lactamases. This study provides additional data on the in vitro antimicrobial activity of cefiderocol and commercially available comparators against an epidemiologically diverse collection of Acinetobacter baumannii clinical isolates. Antimicrobial susceptibility was tested using pre-prepared frozen 96-well microtiter plates containing twofold serial dilutions of: cefepime, ceftazidime/avibactam, imipenem/relebactam, ampicillin/sulbactam, meropenem, meropenem/vaborbactam, ciprofloxacin, minocycline, tigecycline, trimethoprim/sulfamethoxazole and colistin using the standard broth microdilution procedure in cation-adjusted Mueller-Hinton broth (CAMHB). For cefiderocol, iron-depleted CAMHB was used. A collection of 113 clinical strains of A. baumannii isolated from Argentina, Azerbaijan, Croatia, Greece, Italy, Morocco, Mozambique, Peru and Spain were included. The most active antimicrobial agents against our collection were colistin and cefiderocol, with 12.38% and 21.23% of non-susceptibility, respectively. A high proportion of multidrug-resistant (76.77%) and carbapenem-resistant (75.28%) A. baumannii isolates remained susceptible to cefiderocol, which was clearly superior to novel beta-lactam/beta-lactamase inhibitor combinations. Cefiderocol-resistance was higher among carbapenem-resistant isolates and isolates belonging to ST2, but could not be associated with any particular resistance mechanism or clonal lineage. Our data suggest that cefiderocol is a good alternative to treat infections caused by MDR A. baumanni, including carbapenem-resistant strains.

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