Department of Clinical Microbiology, Umeå University, SE-901 85, Umeå, Sweden.
Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark.
Eur J Clin Microbiol Infect Dis. 2022 Jan;41(1):87-97. doi: 10.1007/s10096-021-04352-w. Epub 2021 Oct 2.
Prosthetic joint infection (PJI) is a feared and challenging to diagnose complication after arthroplasty, with Staphylococcus epidermidis as the major pathogen. One important criteria to define PJI is the detection of phenotypically indistinguishable microorganisms with identical antibiotic susceptibility pattern in at least two different samples. However, owing to phenotypical variation within genetic clones and clonal variation within a phenotype, the criteria may be ambiguous. We investigated the extent of diversity among coagulase-negative staphylococci (CoNS) in PJI and characterised S. epidermidis isolates from PJI samples, specifically multiple S. epidermidis isolates identified in individual PJI patients. We performed a retrospective cohort study on 62 consecutive patients with PJI caused by CoNS from two hospitals in Northern Sweden. In 16/62 (26%) PJIs, multiple S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in samples from 40/62 (65%) of the patients using a combination of pulsed-field gel electrophoresis and multilocus sequence typing. Whole-genome sequencing showed the presence of multiple sequence types (STs) in 7/16 (44%) PJIs where multiple S. epidermidis isolates were available. Within-patient phenotypical variation in the antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%) among isolates with the same ST. The results highlight the ambiguity of S. epidermidis phenotypic characterisation as a diagnostic method in PJI and call for larger systematic studies for determining the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and the therapeutic outcomes in patients.
人工关节感染（PJI）是关节置换术后一种令人担忧且难以诊断的并发症，表皮葡萄球菌是主要病原体。定义 PJI 的一个重要标准是在至少两个不同样本中检测到表型上无法区分但抗生素药敏模式相同的微生物。然而，由于遗传克隆内的表型变异和表型内的克隆变异，该标准可能存在歧义。我们研究了 PJI 中凝固酶阴性葡萄球菌（CoNS）之间的多样性程度，并对 PJI 样本中的表皮葡萄球菌分离株进行了特征描述，特别是在单个 PJI 患者中鉴定出的多个表皮葡萄球菌分离株。我们对来自瑞典北部两家医院的 62 例由 CoNS 引起的 PJI 连续患者进行了回顾性队列研究。在 16/62（26%）的 PJI 中，有多个表皮葡萄球菌分离株可用于全基因组分析。通过脉冲场凝胶电泳和多位点序列分型相结合的方法，在 62 例患者中的 40/62（65%）样本中鉴定出了医院适应的多药耐药表皮葡萄球菌遗传克隆。全基因组测序显示，在 7/16（44%）可获得多个表皮葡萄球菌分离株的 PJI 中存在多个序列型（ST）。在具有相同 ST 的分离株中，抗生素药敏表型和/或全基因组抗生素耐药基因含量的患者内表型变异很常见（11/16，69%）。这些结果突出了表皮葡萄球菌表型特征作为 PJI 诊断方法的歧义性，并呼吁进行更大规模的系统研究，以确定 PJI 中 CoNS 多样性的频率、这种多样性对微生物学诊断的影响以及患者的治疗结果。
