Dalbavancin-resistant Staphylococcus epidermidis in vivo selection following a prosthetic joint infection: phenotypic and genomic characterization.

IF 3.7 Q2 INFECTIOUS DISEASES
JAC-Antimicrobial Resistance Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI:10.1093/jacamr/dlae163
L Ruffier d'Epenoux, P Barbier, E Fayoux, A Guillouzouic, R Lecomte, C Deschanvres, C Nich, P Bémer, M Grégoire, S Corvec
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引用次数: 0

Abstract

Background: Dalbavancin is a lipoglycopeptide antibiotic with a wide spectrum of activity against Gram-positive bacteria, including MDR isolates. Its pharmacokinetic properties and administration patterns could be useful for the treatment of bone and joint infections, especially prosthetic joint infections (PJIs).

Introduction: We report the case of an 80-year-old man who experienced an acute periprosthetic joint infection of his right total knee arthroplasty (TKA). A DAIR procedure was done with tissue sampling, which allowed identification of a linezolid-resistant MDR S. epidermidis (LR-MDRSE) strain. The patient was then treated with dalbavancin (four injections).

Methods: We studied the phenotypic and genomic evolution of the strains and plasma through concentrations of dalbavancin at different points in time.

Results: After four injections (1500 mg IV) of dalbavancin over a 6 month period, the dalbavancin MIC increased 4-fold. Calculated fAUC0-24/MIC ratios were 945, 1239 and 766.5, respectively, at Days 49, 71 and 106, assuming an MIC of 0.032 mg/L. The PFGE dendrogram revealed 97% similarity among all the isolates. These results suggest acquisition by the S. epidermidis strain of dalbavancin resistance when the patient underwent dalbavancin treatment. A 4-amino-acid deletion in the walK gene coinciding with the emergence of phenotypic resistance was revealed by WGS without any other relevant indels.

Conclusions: Despite dalbavancin treatment with pharmacokinetic management, emerging dalbavancin resistance in S. epidermidis was observed, resulting in treatment failure. This outcome led to a prosthesis revision and long-term suppressive antibiotic therapy, with no recurrence of PJI after an 18 month follow-up.

假体关节感染后表皮葡萄球菌的体内选择:表型和基因组特征。
背景:达尔巴万星(Dalbavancin)是一种脂糖肽抗生素,对革兰氏阳性细菌(包括MDR分离株)具有广谱活性。它的药代动力学特性和给药模式可用于治疗骨关节感染,尤其是假体关节感染(PJI):我们报告了一例 80 岁男性右全膝关节置换术(TKA)急性假体关节周围感染的病例。通过组织取样进行了 DAIR 手术,确定了耐利奈唑胺 MDR 表皮葡萄球菌(LR-MDRSE)菌株。随后,患者接受了达巴万星治疗(注射四次):方法:我们通过不同时间点的达巴万星浓度研究了菌株和血浆的表型和基因组演变:结果:在6个月内注射4次(1500毫克静脉注射)达巴万星后,达巴万星的MIC增加了4倍。假设 MIC 为 0.032 mg/L,计算得出的 fAUC0-24/MIC 比率在第 49、71 和 106 天分别为 945、1239 和 766.5。PFGE 树枝图显示所有分离物之间的相似度为 97%。这些结果表明,患者在接受达巴万星治疗时,表皮葡萄球菌菌株获得了达巴万星耐药性。WGS发现,在出现表型耐药性的同时,walK基因中出现了4个氨基酸缺失,但没有发现其他相关的indels:结论:尽管通过药物动力学管理进行了达巴万星治疗,但仍观察到表皮葡萄球菌出现了达巴万星耐药性,导致治疗失败。这一结果导致假体翻修和长期抗生素抑制治疗,随访18个月后PJI未再复发。
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
CiteScore
5.30
自引率
0.00%
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审稿时长
16 weeks
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