Characterization of Klebsiella pneumoniae Isolates from Croatia Resistant to Cefiderocol

Background/Objectives: We conducted this study to evaluate the genotypic and pheno-typic profiles of carbapenem resistant K. pneumoniae (CRKP)isolates, exhibiting resistance to cefiderocol (FDC) focusing on antibiotic susceptibility, β-lactamase production, genetic environment of blaCARB and blaESBLgenes and molecular epidemiology. FDC is now last line antibiotic for severe infections due to CRKP: Methods: Susceptibility to a wide range of antibiotics including carbapenems was deter-mined by disk-diffusion and broth microdilution method. Carbapenemases were screened by modified Hodge test while carbapenem hydrolysis was investigated by CIM and eCIM test. The screening for β-lactamase and fluroquinolone resistance genes was carried out by PCR. Encoding plasmids were characterized by PCR-based replicon typing (PBRT). Inter array-chip test and whole genome sequencing were applied on selected isolates. Results: All of the 31 tested isolates exhibited high level resistance to amoxicil-lin-clavulanate, piperacillin-tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESC), cefepime, ceftolozan-tazobactam and ciprofloxacin and the majority to gentamicin, and amikacin. Colistin preserved activity against 71% and ceftazidime-avibactam against 87% of the isolates. Combined disk method with clavulanic acid was positive in all but one isolate, indicating production of an ESBL. Twenty-eight isolates carried one single carbapenemase encoding gene whereas three harbored double blaCARB genes. Among studied isolates 61 % carried blaOXA-48, 29% blaKPC and four blaNDM genes... Interarry chip test and WGS identified additional aminoglycoside, sulphonamide and trimethorpim re-sistance genes Conclusion: To our knowledge, this is the first study on FDC resistance in Croatia. The diffusion of FDR resistant isolates was detected in both hospital and outpatient setting emphasizing the need for “One Health” approach.