TY - JOUR
T1 - Characterization of Klebsiella pneumoniae Isolates Resistant to Cefiderocol from Hospitals and Outpatient Settings in Croatia
AU - Bedenić, Branka
AU - Luxner, Josefa
AU - Zarfel, Gernot
AU - Benčić, Ana
AU - Sardelić, Sanda
AU - Anušić, Maja
AU - Vraneš, Jasmina
AU - Dobretzberger, Verena
AU - Barišić, Ivan
AU - Grisold, Andrea
PY - 2025/2/4
Y1 - 2025/2/4
N2 - Background/Objectives: We conducted this study to evaluate the genotypic and phenotypic profiles of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, exhibiting resistance to cefiderocol (FDC), focusing on antibiotic susceptibility, β-lactamase production, the genetic environment of blaCARB and blaESBL genes and molecular epidemiology. FDC is now a last-line antibiotic for severe infections due to CRKP. Methods: Susceptibility to a wide range of antibiotics was determined by the disk diffusion and broth microdilution method. Carbapenemases were screened by a modified Hodge test while carbapenem hydrolysis was investigated using mCIM and eCIM tests. The screening for β-lactamase and fluoroquinolone cluster resistance genes was carried out by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). An inter-array genotyping CarbaResist test and whole genome sequencing (WGS) were applied on selected isolates. Results: All of the 31 isolates studied exhibited high-level resistance to amoxicillin–clavulanate, piperacillin–tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESC), cefepime, ceftolozan–tazobactam and ciprofloxacin and the majority to gentamicin, and amikacin. Colistin and ceftazidime–avibactam preserved activity against 71% and 87% of the isolates, respectively. The combined disk method with clavulanic acid was positive in all but one isolate, indicating the production of an ESBL. Twenty-eight isolates carried one single carbapenemase-encoding gene, whereas three harbored double blaCARB genes. Among the studied isolates, 61% carried blaOXA-48, 29% blaKPC and 12.9% blaNDM genes. The inter-array genotyping CarbaResist test and WGS identified additional aminoglycoside-, sulphonamide- and trimethoprim-resistance genes. Conclusion: To our knowledge, this is the first study on FDC resistance in Croatia. The diffusion of FDC-resistant isolates was detected in both hospital and outpatient settings, emphasizing the need for a “One Health” approach.Keywords: Klebsiella pneumoniae; cefiderocol; OXA-48; KPC; metallo-β-lactamase
AB - Background/Objectives: We conducted this study to evaluate the genotypic and phenotypic profiles of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, exhibiting resistance to cefiderocol (FDC), focusing on antibiotic susceptibility, β-lactamase production, the genetic environment of blaCARB and blaESBL genes and molecular epidemiology. FDC is now a last-line antibiotic for severe infections due to CRKP. Methods: Susceptibility to a wide range of antibiotics was determined by the disk diffusion and broth microdilution method. Carbapenemases were screened by a modified Hodge test while carbapenem hydrolysis was investigated using mCIM and eCIM tests. The screening for β-lactamase and fluoroquinolone cluster resistance genes was carried out by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). An inter-array genotyping CarbaResist test and whole genome sequencing (WGS) were applied on selected isolates. Results: All of the 31 isolates studied exhibited high-level resistance to amoxicillin–clavulanate, piperacillin–tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESC), cefepime, ceftolozan–tazobactam and ciprofloxacin and the majority to gentamicin, and amikacin. Colistin and ceftazidime–avibactam preserved activity against 71% and 87% of the isolates, respectively. The combined disk method with clavulanic acid was positive in all but one isolate, indicating the production of an ESBL. Twenty-eight isolates carried one single carbapenemase-encoding gene, whereas three harbored double blaCARB genes. Among the studied isolates, 61% carried blaOXA-48, 29% blaKPC and 12.9% blaNDM genes. The inter-array genotyping CarbaResist test and WGS identified additional aminoglycoside-, sulphonamide- and trimethoprim-resistance genes. Conclusion: To our knowledge, this is the first study on FDC resistance in Croatia. The diffusion of FDC-resistant isolates was detected in both hospital and outpatient settings, emphasizing the need for a “One Health” approach.Keywords: Klebsiella pneumoniae; cefiderocol; OXA-48; KPC; metallo-β-lactamase
UR - https://doi.org/10.3390/antibiotics14020154
U2 - 10.3390/antibiotics14020154
DO - 10.3390/antibiotics14020154
M3 - Article
SN - 2079-6382
VL - 14
JO - Antibiotics
JF - Antibiotics
IS - 2
ER -