Characterization of Klebsiella pneumoniae Isolates Resistant to Cefiderocol from Hospitals and Outpatient Settings in Croatia

TL;DR

This study characterizes cefiderocol-resistant Klebsiella pneumoniae isolates in Croatia, revealing their antibiotic resistance profiles and genetic traits.

Contribution

This is the first study in Croatia on cefiderocol resistance in Klebsiella pneumoniae, highlighting its spread in both hospital and outpatient settings.

Findings

All 31 isolates showed high resistance to multiple antibiotics, including amoxicillin–clavulanate and cefepime.

61% of isolates carried the blaOXA-48 gene, while 29% and 12.9% carried blaKPC and blaNDM genes, respectively.

Ceftazidime–avibactam and colistin showed preserved activity against 87% and 71% of isolates, respectively.

Abstract

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.