Evaluation of cefiderocol activity against Gram-negative bacilli isolated from a university hospital in the city of São Paulo

Abstract

Cefiderocol is a promising antimicrobial approved by the Food and Drug Administration (FDA-USA) and the European Medicines Agency (EMA). It is a last-resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially CR Enterobacterales, metallo-beta-lactamase-producing Pseudomonas aeruginosa and CR Acinetobacter baumannii. However, as it is a new therapeutic option, data on the activity of cefiderocol in low- and middle-income countries, such as Brazil, is still scarce. In this sense, the aim of this project is to investigate the activity of cefiderocol, as well as to compare different susceptibility tests of this antimicrobial drug against Gram-negative bacilli from a university hospital in the city of São Paulo, Brazil. For this purpose, 350 isolates of different bacterial species (Escherichia coli, Klebsiella pneumoniae, P. aeruginosa, A. baumannii and Stenotrophomonas maltophilia) collected from blood samples of patients (previously anonymized) who had bloodstream infection will be tested, as well as from other clinical significant sites in other patients. The isolates used are kept in the Microorganism Biorepository of the Laboratório de Microbiologia Clínica (LEMC) of the Universidade Federal de São Paulo - UNIFESP. The species will be confirmed through the Matrix Assisted Laser Desorption Ionization - Time of Flight - Mass Spectrometry (MALDI-TOF MS) technique. The susceptibility profile of the isolates will be evaluated through the disk diffusion test and broth microdilution with 20 antimicrobial drugs. In addition, a rapid cefiderocol NP susceptibility test will be performed to compare its efficacy and specificity to other sensitivity tests. For isolates that present a carbapenem resistance profile, the carbapenemase-production evaluation will be perfomed by using the Blue-Carba technique and the molecular characterization of the genes encoding ESBL and cabapenemases. Isolates categorized as resistant to cefiderocol will be selected for whole genome sequencing to understand the mechanism leading to cefiderocol resistance.