Gram-negative and Gram-positive bacteria induce different osteolysis progression profiles over time in fracture-related infections.

Abstract

The presence of bacteria in bones may lead to osteolysis, potentially compromising fracture healing. While radiographic assessment is essential for identifying osteolysis, the relationship between causative pathogens and visible radiolucency in fracture-related infections (FRI) remains poorly understood. This study aimed to evaluate the association between causative organisms, host factors, and radiographic osteolysis in unhealed FRIs. This retrospective study included 79 patients with unhealed FRIs, with available microbiological data and serial radiographs from the time of initial fracture fixation to index surgery for infection. Osteolysis was scored using a modified Mirel's-based severity scale, classifying cortical, medullary, and combined bone loss relative to adjacent normal bone. Pathogens were categorized as: (1) Gram-negative bacteria (GN), (2) Staphylococcus aureus, (3) other Gram-positive bacteria (GP), (4) polymicrobial (PM) (Gram-positive and Gram-negative bacteria), and (5) culture negative (CN). Patients had a median of two radiographs (IQR 1.5-4) over a median of 81 days (IQR 28-216), after fracture fixation. Host factors were not associated with osteolysis severity. The 79 cases were distributed as: 17 GN, 19 S. aureus, 17 GP, 17 CN, and 9 PM infections. All pathogens induced degrees of osteolysis but the progression of bone loss over time was different between groups. Gram-negative infections showed the fastest and most aggressive bone loss, with a 4.3-fold increase in osteolysis severity compared to CN cases (p = 0.001). S. aureus and polymicrobial infections showed 1.8- and 2.9-fold increases, respectively. Gram-negative pathogens pose significant clinical challenges and there is an urgent need to broaden the focus on GN infections in FRIs. This study provides new clinical insights into the role of pathogen-specific osteolytic patterns in FRIs. Gram-negative bacteria exhibit the most rapid and destructive bone loss, emphasizing the need for early recognition and timely intervention. Radiographic osteolysis appearing early should raise suspicion for GN infections. These findings also highlight the need for basic science models to expand beyond S. aureus and better address the underexplored osteolytic potential of GN organisms.