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

IF 3.9 2区医学 Q1 INFECTIOUS DISEASES Journal of Antimicrobial Chemotherapy Pub Date : 2024-11-04 DOI:10.1093/jac/dkae312

Rebecka Widerström, Mia Aarris, Susanne Jacobsson, Marc Stegger, Bo Söderquist, Emeli Månsson

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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.

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探索磷霉素的潜力：假体关节感染中表皮葡萄球菌的药敏试验和耐药性研究。

背景：对于由耐多药表皮葡萄球菌（MDRSE）引起的人工关节感染（PJI），目前的治疗方案十分有限。磷霉素（FOF）作为一种潜在的治疗方法已受到关注，但有关表皮葡萄球菌（包括 MDRSE）的表型和基因型敏感性的信息却很少：调查瑞典前瞻性收集的表皮葡萄球菌分离株对 FOF 的表型和基因型敏感性：方法：使用内部琼脂稀释法（AD）和商业 AD 面板测定 MIC。分析了与 FOF 耐药性相关的基因和基因变异：FOF对所有分离株都有抑制作用，只有一种分离株除外，该分离株的MIC大于256 mg/L。商业 AD 检验小组的整体表现良好，但往往会高估 MIC，结果与金标准的基本一致率为 84%。利用全基因组测序（WGS）数据的公开工具进行的基因组分析表明，所有分离物都具有基因型 FOF 耐药性，但深入分析发现，与 FOF 耐药性相关的 fosB 只存在于表型耐药性分离物中。没有检测到与 FOF 抗性相关的其他基因或基因变异：结论：对 FOF 的表型耐药性和 fosB 的存在在该菌种中很少见，这表明 FOF 有可能成为治疗表皮葡萄球菌的一种选择。商品化的 AD 检测板具有很高的可重复性，但与参考方法相比，EA 的效果并不理想。使用 WGS 数据通用工具得出的 FOF 基因型耐药性结果应进行严格评估，并与表皮葡萄球菌的相关 fosB 参考文献进行适当验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Antimicrobial Chemotherapy 医学-传染病学

CiteScore

9.20

自引率

5.80%

发文量

423

审稿时长

2-4 weeks

期刊介绍： The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.