Evaluation of Different Techniques for Antimicrobial Susceptibility Tests of Cefiderocol Against Enterobacterales Isolated from Brazilian Hospitals

• Grant number: 24/14053-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2025
• Field of knowledge: Health Sciences - Collective Health
• Principal Investigator: Ana Cristina Gales
• Grantee: Silvio Cardoso Vieira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

The presence of multidrug-resistant Gram-negative bacilli (GNB) is a current concernin the hospital setting due to the difficulty in antimicrobial therapy for infected patients (WHO,2024). Despite the development of many antimicrobials, treatment remains challenging forsome groups, including carbapenem-resistant Enterobacterales, multidrug-resistantPseudomonas aeruginosa, and several other non-fermenting glucose Gram-negative organisms(e.g., Acinetobacter baumannii complex, Stenotrophomonas maltophilia, and Burkholderiacepacia complex) (Tacconelli et al., 2018).Cefiderocol is a new cephalosporin approved by both the United States Food and DrugAdministration (FDA) and European Medicine Agency (EMA). Preclinical and clinical testsindicate that cefiderocol is an important alternative for the treatment of infections caused bycarbapenem-resistant Gram-negative bacilli especially for those producers of metallo-betalactamases (McCreary; Heil; Tamma, 2021). Prior to the use of cefiderocol, it is important toperform a susceptibility test (Kolesnik-Goldmann et al., 2023). The broth microdilution withiron-depleted Mueller-Hinton broth (ID-CAMHB) is the "gold standard" methodology fordetermining susceptibility to cefiderocol by both the Clinical and Laboratory StandardsInstitute (CLSI, 2024) and the European Committee on Antimicrobial Susceptibility Testing(EUCAST, 2024). However, The preparation of a special medium for cefiderocol susceptibilitytesting increases the workload in microbiology laboratories and complicates its implementationin routine procedures (Liu et al., 2023).The disk diffusion (DD) technique for determining susceptibility to cefiderocol is alsorecommended by CLSI and EUCAST. This technique is considered more friendly for routineUniversidade Federal de São Paulo - UNIFESPEscola Paulista de Medicina - EPMDepartment of Medicineuse in clinical laboratories since it does not require iron removal from the medium (Bovo etal., 2023). However, according to EUCAST, it works as a screening test and does not eliminatethe need for BMD when isolates show disk diffusion zones d 23mm. In addition, both tests(BMD and DD) take 18-24 hours to obtain final results (Nayak et al., 2022). Cefiderocol NPrapid test has been suggested as an alternative method for evaluating cefiderocol susceptibility.This test detects bacterial growth in the presence of cefiderocol by a color change providingresults within 3 hours (Nordmann et al., 2022).Due to the lack of studies comparing the sensitivity and specificity of differentmethodologies (BMD, DD, and NP test) for determining cefiderocol susceptibility amongEnterobacterales isolated from Brazilian hospitals, it is crucial to compare these tests. Suchcomparisons are important for identifying their reliability and reproducibility, given theirdifferences in their execution methods and turnaround times. These factors are essential in aclinical context because the speed and accuracy of results can significantly improve patienttreatment outcomes.