Mechanisms of Antibiotic Failure During Staphylococcus aureus Osteomyelitis.

Brittney D Gimza,James E Cassat

doi:10.3389/fimmu.2021.638085

Abstract

Staphylococcus aureus 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 S. aureus 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 S. aureus. 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.

Highlights

Staphylococcus aureus is the leading cause of osteomyelitis, which is defined as inflammation of bone but is most commonly encountered in the setting of bacterial infection
Bone infections typically develop via three clinical mechanisms, including hematogenous seeding of bone, invasion of bone from a contiguous source, or infection occurring secondary to vascular insufficiency or neuropathy [1]
The treatment of acute osteomyelitis using antibiotic therapy is associated with a high success rate [3]; many cases require surgical debridement in addition to antibiotic therapy and despite these measures, treatments fail in ∼20% of cases [4]

Summary

Introduction

Staphylococcus aureus is the leading cause of osteomyelitis, which is defined as inflammation of bone but is most commonly encountered in the setting of bacterial infection. S. aureus immunoevasive factors contribute to the formation of abscesses, which are the characteristic tissue lesions of invasive staphylococcal infection and consist of a threedimensional community of bacteria surrounded by immune cells. S. aureus biofilm formation on necrotic bone and implanted material greatly contributes to bacterial persistence during bone infection, and is presumed to be a leading cause of treatment recalcitrance during chronic osteomyelitis [19, 20].

Results

Conclusion