Probing fosfomycin’s potential: a study on susceptibility testing and resistance in Staphylococcus epidermidis from prosthetic joint infections

Author:

Widerström Rebecka1,Aarris Mia2ORCID,Jacobsson Susanne3,Stegger Marc245,Söderquist Bo34ORCID,Månsson Emeli6

Affiliation:

1. Department of Laboratory Medicine, Region Västmanland , Västerås , Sweden

2. Department of Bioinformatics, Statens Serum Institut , Copenhagen , Denmark

3. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University , Örebro , Sweden

4. School of Medical Sciences, Faculty of Medicine and Health, Örebro University , Örebro , Sweden

5. Antimicrobial Resistance and Infectious Diseases Laboratory, Harry Butler Institute, Murdoch University , Perth , Australia

6. Region Västmanland – Uppsala University, Centre for Clinical Research, Västmanland Hospital Västeras , Västerås , Sweden

Abstract

Abstract Background There are limited treatment options for prosthetic joint infections (PJI) due to multidrug-resistant Staphylococcus epidermidis (MDRSE). Fosfomycin (FOF) has gained attention as a potential therapy, but there is a paucity of information on the phenotypic and genotypic susceptibility amongst S. epidermidis, including MDRSE. Objectives To investigate phenotypical and genotypical susceptibility to FOF in S. epidermidis isolates prospectively collected from PJIs in Sweden. Methods MIC determination was performed using in-house agar dilution (AD) and a commercial AD panel. Genes and gene variants associated with FOF resistance were analysed. Results Multidrug resistance was common [74/89 (83%) isolates were MDRSE]. FOF inhibited all isolates except one, which had an MIC > 256 mg/L. The commercial AD panel demonstrated good overall performance but tended to overestimate the MIC, resulting in 84% essential agreement with the gold standard. Genomic analysis with publically available tools for whole-genome sequencing (WGS) data suggested genotypic FOF resistance in all isolates, but in-depth analysis revealed that fosB, associated with FOF resistance, was only present in the phenotypically resistant isolate. No other genes or gene variants associated with FOF resistance were detected. Conclusions Phenotypic resistance to FOF and presence of fosB were rare in this collection, indicating FOF’s potential as a treatment option for S. epidermidis. The commercial AD panel demonstrated high reproducibility, but EA with the reference method was less than optimal. Findings of genotypic FOF resistance using common tools for WGS data should be critically evaluated and appropriately verified with relevant fosB references for S. epidermidis.

Funder

Nyckelfonden at Örebro University Hospital

Region Västmanland

Publisher

Oxford University Press (OUP)

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