Antimicrobial resistance: Biofilms, small colony variants, and intracellular bacteria.

Soft tissue and bone infections continue to be a serious complication in orthopedic and trauma surgery. Both can lead to a high burden for the patients and the healthcare system. Musculoskeletal infections can be induced by intraoperative contamination, bacterial contamination of open wounds or hematogenous bacterial spread. During the recent decades, advances were achieved in the understanding of pathogenesis and antibiotic resistance. Despite some progress in the diagnosis and advancing of therapeutic concepts, groundbreaking successful improvement of treatment concepts is still missing. Current therapy concepts are based on the two pillars consisting of surgical debridement with joint or bone reconstruction as well as prolonged antibiotic therapy. An improved understanding of both host and pathogen-related factors leading to treatment failure is essential in musculoskeletal infections. Therefore, this review aims to give an overview of pathogen-related pathophysiology in musculoskeletal infections. It describes defense strategies of pathogens such as (1) biofilm, its development, characteristics, and treatment options. In addition, (2) characteristics of small colony variants and (3) intracellular bacteria are highlighted. Lastly (4) an outlook for potential and promising future therapeutic strategies is provided.