Assessment of the Anti-Biofilm Effect of Cefiderocol Against 28 Clinical Strains of Multidrug-Resistant Gram-Negative...

Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of MDR Gram-negative bacilli isolated from clinical samples of Pseudomonas aeruginosa (n = 5), Acinetobacter baumannii (n = 11), and Klebsiella pneumoniae (n = 12). We first determined the minimum inhibitory concentration (MIC) of each strain using the microdilution method. We also defined the minimum biofilm inhibitory concentration (MBIC) as a ≥50% reduction in tetrazolium salt (XTT) (as recommended in the 2017 Spanish Microbiology Protocols [SEIMC] for the microbiological diagnosis of infections related to the formation of biofilms). We also analyzed the reduction in the following biofilm variables after an 8 mg/mL FDC treatment: the CFU count, the cell viability, the biomass, the metabolic activity, and extracellular α or β polysaccharides. Results: The MIC₅₀ and MBIC₅₀ of FDC were 0.5 mg/L and 64 mg/L, respectively. We observed a mean (SD) fold increase in the susceptibility to FDC between planktonic and sessile cells for P. aeruginosa, A. baumannii, and K. pneumoniae of 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/mL of FDC was tested, we observed that the best median (IQR) percentage reductions were obtained for cell viability and the extracellular matrix (73.1 [12.4-86.5] and 79.5 [37.3-95.5], respectively), particularly for P. aeruginosa. The lowest percentage reduction rates were those obtained for biomass. Conclusions: We demonstrated that the susceptibility to FDC was significantly reduced when strains were in a biofilm state. The best percentage reduction rates for all biofilm-defining variables were observed for P. aeruginosa. Our results need to be validated using a larger collection of clinical samples.