Sekar Amita, Fan Yingfang, Tierney Peyton, McCanne Madeline, Jones Parker, Malick Fawaz, Kannambadi Devika, Wannomae Keith K, Inverardi Nicoletta, Muratoglu Orhun K, Oral Ebru
Harris Orthopaedics laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Department of Orthopaedic Surgery, Harvard Medical School, Boston, Massachusetts 02115, United States.
ACS Infect Dis. 2024 Dec 13;10(12):4156-4166. doi: 10.1021/acsinfecdis.4c00409. Epub 2024 Dec 4.
With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilms are crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better treatment outcomes. We use in vivo and in vitro implant-associated infection models to demonstrate that methicillin-sensitive and resistant (MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA, and the models could capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can guide clinical dosing to prevent or treat PJI effectively.
随着用于治疗顽固性感染的抗生素洗脱聚合物材料的出现，利用临床前模型研究生物膜对于提高人工关节周围感染的治疗效果至关重要。为了建立一个具有更好治疗效果的有效临床给药框架，需要对感染的风险和严重程度进行分层。我们使用体内和体外植入相关感染模型来证明，甲氧西林敏感和耐药（MSSA和MRSA）具有依赖模型的不同植入物和植入周围组织定植模式。发现生物膜的成熟度和位置（植入物与组织）会影响MSSA和MRSA的抗生素敏感性演变概况，并且这些模型可以捕捉体内不同的宿主-微生物相互作用。基因表达研究揭示了定植细菌群体的分子异质性。本研究中对不同临床前模型中感染风险和严重程度的比较和分层可为临床给药提供指导，以有效预防或治疗人工关节感染。
