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.

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.

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