Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient’s conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed. Overall, 28 patients were included. Ten patients (35.71%) had ventilator-associated pneumonia (VAP), ten (35.71%) had a bloodstream infection (BSI), and eight (28.57%) were only colonized. Recurrent infection occurred in 25% (5/20) of infected patients. Two different strains of A. baumannii were isolated from the index patient of the first outbreak. The first strain belonged to the ST85 and carried the bla_NDM-1 carbapenemase gene, while the second belonged to the ST2 and carried bla_OXA-23, and bla_OXA-66 carbapenemase genes. The phylogenetic analysis revealed that the ST2 strain was the cause of the major outbreak, and mutations in the AmpC gene were related to progressive increasing minimum inhibitory concentration (MIC) and finally, cefiderocol-resistance in one strain. The CRAB isolates from the second outbreak were also identified as ST2. Cefiderocol-resistant strains tests identified by the disc diffusion method were involved in 24% (6/25) of nosocomial infections. Using broth microdilution (BMD) ComASP^® only, 33.3% (2/6) of these strains were cefiderocol-resistant. All-cause ICU mortality was 21.4%. Conclusions: Cefiderocol is the first approved siderophore cephalosporin for the treatment of CRAB infections. Cefiderocol-resistant strains were related with bla_NDM-1 carbapenemase and mutations in the AmpC gene. Cefiderocol-resistant strains or that cannot be properly interpreted by disk diffusion, should be retested using BMD for definitive categorization.

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.