# Cefiderocol Comparative Resistance and Clinical Predictors in CRE-BSI: Data from an OXA-48–Endemic Region with Rising OXA-48/NDM Coproducers

## TL;DR

This study examines cefiderocol's effectiveness against drug-resistant bacteria in Turkey, finding it highly effective but noting resistance in high-risk patients.

## Contribution

The study provides baseline susceptibility data and clinical predictors of cefiderocol resistance in an OXA-48–endemic region with emerging NDM coproducers.

## Key findings

- Cefiderocol showed 94% susceptibility against CRE-BSI isolates, outperforming CAZ-AVI and colistin.
- Cefiderocol resistance was linked to hematologic malignancy, prior antibiotic use, and prolonged hospitalization.
- The study highlights the need for surveillance and stewardship before cefiderocol becomes available in Turkey.

## Abstract

Background/Objectives: Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CREs) are a growing public health threat due to limited therapeutic options and high mortality. In Turkey, oxacillinase-48 (OXA-48) producers predominate, while OXA-48/New Delhi metallo-β-lactamase (NDM) co-producers are increasingly detected. Although ceftazidime–avibactam (CAZ-AVI) is effective against OXA-48, treating NDM-positive isolates remains challenging. Cefiderocol, a novel siderophore cephalosporin active against both serine- and metallo-β-lactamases, is not yet available in Turkey. Establishing baseline susceptibility rates and identifying clinical predictors of resistance are, therefore, crucial before its introduction. Methods: This retrospective study included adult patients with CRE-BSIs diagnosed at a tertiary university hospital in Istanbul between January and December 2023. Demographic, clinical, and microbiological data were collected from electronic medical records. Susceptibility to cefiderocol, CAZ-AVI, and colistin was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 criteria. Risk factors for cefiderocol resistance were analyzed. Results: Among 202 isolates, cefiderocol showed the highest susceptibility (94%, n = 190), followed by CAZ-AVI (82%, n = 166) and colistin (70%, n = 141), with all pairwise differences being statistically significant (p < 0.001). Cefiderocol resistance (6%, n = 12) was significantly associated with hematologic malignancy, hematopoietic stem cell transplantation, prior CAZ-AVI or polymyxin exposure, prolonged hospitalization, and repeated admissions. Conclusions: Cefiderocol demonstrated potent in vitro activity against CRE-BSI isolates, with resistance confined to distinct high-risk clinical settings. This pre-implementation study provides baseline microbiological and epidemiological data from an OXA-48 endemic region with rising NDM prevalence, underscoring the importance of early surveillance and stewardship strategies before cefiderocol becomes clinically available.