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Probing fosfomycin's potential: a study on susceptibility testing and resistance in Staphylococcus epidermidis from
Rebecka Widerström1, Mia Aarris2, Susanne Jacobsson3
1Department of Laboratory Medicine, Region Västmanland, Västerås, Sweden.
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.
Insights
Fosfomycin (FOF) shows potential for treating prosthetic joint infections (PJI) caused by multidrug-resistant Staphylococcus epidermidis (MDRSE). Phenotypic resistance and the fosB gene were rare in this study, suggesting FOF is a viable option.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Prosthetic joint infections (PJI) present limited therapeutic options, particularly those caused by multidrug-resistant Staphylococcus epidermidis (MDRSE).
- Fosfomycin (FOF) is a potential treatment, but susceptibility data for S. epidermidis, including MDRSE, is scarce.
Purpose of the Study:
- To evaluate the phenotypic and genotypic susceptibility of S. epidermidis isolates from PJIs to Fosfomycin (FOF).
- To assess the utility of commercial agar dilution (AD) panels and whole-genome sequencing (WGS) for determining FOF resistance.
Main Methods:
- MIC determination using in-house and commercial AD panels.
- Analysis of genes and variants associated with FOF resistance via whole-genome sequencing (WGS).
Main Results:
- High prevalence of multidrug resistance (83% MDRSE).
- Fosfomycin (FOF) inhibited all but one isolate (MIC > 256 mg/L).
- Genomic analysis indicated fosB, linked to FOF resistance, was present only in the resistant isolate.
Conclusions:
- Phenotypic resistance to FOF and the presence of fosB are rare in S. epidermidis from PJIs, supporting FOF as a treatment option.
- Commercial AD panels showed good reproducibility but suboptimal essential agreement.
- Genotypic resistance findings from WGS require critical evaluation against specific resistance genes like fosB.
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