Cefiderocol Comparative Resistance and Clinical Predictors in CRE-BSI: Data from an OXA-48-Endemic Region with Rising...

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) pose a significant global health threat due to limited treatment options.
• Oxacillinase-48 (OXA-48) producing CRE are prevalent in Turkey, with increasing detection of OXA-48/New Delhi metallo-β-lactamase (NDM) co-producers.
• Ceftazidime-avibactam (CAZ-AVI) is effective against OXA-48 but less so against NDM-producing CRE, highlighting the need for new therapeutic agents like cefiderocol.

Purpose of the Study:

• To establish baseline cefiderocol susceptibility rates against CRE-BSIs in Turkey.
• To identify clinical predictors of cefiderocol resistance in this patient population.
• To provide pre-implementation data for cefiderocol, a novel antibiotic not yet available in Turkey.

Main Methods:

• Retrospective analysis of adult patients with CRE-BSIs at a tertiary university hospital in Istanbul (January-December 2023).
• Collection of demographic, clinical, and microbiological data from electronic medical records.
• Determination of in vitro susceptibility to cefiderocol, CAZ-AVI, and colistin using European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 criteria.

Main Results:

• Cefiderocol exhibited the highest susceptibility rate (94%) among 202 CRE isolates, followed by CAZ-AVI (82%) and colistin (70%).
• Cefiderocol resistance (6%) was significantly associated with hematologic malignancy, stem cell transplantation, prior exposure to CAZ-AVI or polymyxins, prolonged hospitalization, and repeated admissions.
• Statistically significant differences (p < 0.001) were observed in susceptibility rates between the tested antibiotics.

Conclusions:

• Cefiderocol demonstrates potent in vitro activity against prevalent CRE-BSI isolates in an OXA-48 endemic region with rising NDM prevalence.
• Cefiderocol resistance is associated with specific high-risk clinical settings and patient factors.
• This study underscores the importance of pre-implementation surveillance and antimicrobial stewardship strategies for cefiderocol in Turkey.