Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.
Front Immunol. 2021 Feb 12;12:638085. doi: 10.3389/fimmu.2021.638085. eCollection 2021.
is a highly successful Gram-positive pathogen capable of causing both superficial and invasive, life-threatening diseases. Of the invasive disease manifestations, osteomyelitis or infection of bone, is one of the most prevalent, with serving as the most common etiologic agent. Treatment of osteomyelitis is arduous, and is made more difficult by the widespread emergence of antimicrobial resistant strains, the capacity of staphylococci to exhibit tolerance to antibiotics despite originating from a genetically susceptible background, and the significant bone remodeling and destruction that accompanies infection. As a result, there is a need for a better understanding of the factors that lead to antibiotic failure in invasive staphylococcal infections such as osteomyelitis. In this review article, we discuss the different non-resistance mechanisms of antibiotic failure in . We focus on how bacterial niche and destructive tissue remodeling impact antibiotic efficacy, the significance of biofilm formation in promoting antibiotic tolerance and persister cell formation, metabolically quiescent small colony variants (SCVs), and potential antibiotic-protected reservoirs within the substructure of bone.
是一种非常成功的革兰氏阳性病原体，能够引起浅表和侵袭性、危及生命的疾病。在侵袭性疾病表现中，骨髓炎或骨感染是最常见的一种， 是最常见的病原体。骨髓炎的治疗很艰难，而且由于抗菌药物耐药菌株的广泛出现、葡萄球菌即使起源于遗传易感性背景也能表现出对抗生素的耐受性的能力，以及感染伴随的显著骨重塑和破坏，使得治疗更加困难。因此，需要更好地了解导致骨髓炎等侵袭性葡萄球菌感染中抗生素失败的因素。在这篇综述文章中，我们讨论了 中抗生素失败的不同非耐药机制。我们重点讨论了细菌生态位和破坏性组织重塑如何影响抗生素疗效、生物膜形成在促进抗生素耐受性和持续存在细胞形成中的意义、代谢静止的小菌落变异体 (SCV) 以及骨亚结构内潜在的抗生素保护储库。
