Do Paired Microbiology and Histology Have a Place in Chronic Osteomyelitis and Fracture-Related Infections?

Background Microbiological culture and histology are independent diagnostic criteria in chronic osteomyelitis (cOM) and fracture-related infection (FRI). However, the prognostic value of combining these modalities within the same tissue sample has rarely been investigated. Therefore, this study examined whether paired microbiological and histological assessments could provide additional insight into disease severity. We hypothesized that increased numbers of neutrophils and osteoclasts would be associated with culture-positive samples, and that samples positive on both microbiology and histology would reflect more severe disease. Methods In this prospective single-centre study, adults undergoing surgery for confirmed FRI or cOM were included. Clinical and disease classification data (FRI and BACH) were recorded. Five deep-tissue samples were collected intraoperatively and divided for microbiological culture and histological assessment of osteoclasts and neutrophil infiltration. Histological positivity was defined as having more than 5 neutrophils per high-power field (x400) in accordance with international diagnostic guidelines. Microbiological positivity was defined as a positive culture. Microbiological diagnostic confirmation of infection in the individual patient was defined by isolating phenotypically indistinguishable pathogens from at least 2/5 separate samples. Results Forty-one patients were included (11 cOM, 30 FRI), of whom 68% received preoperative antibiotics. Over 60% of patients in the cohort had poorly controlled comorbidities. Nineteen patients (46%) were diagnosed as culture-positive, while 32 patients (78%) were histologically positive. Among the 205 samples (5 from each patient), 31% were culture-positive, 56% histology-positive, and 26% double-positive. Histological scores were significantly higher in culture-positive samples (p <0.001). Treatment failure occurred in seven patients (18%), all with FRI. Paired positive samples were associated with increased odds of clinical failure and earlier revision, with odds increasing 1.68-fold for each additional paired positive sample (95% CI, 1.10–2.77). The distribution of osteoclasts did not differ substantially between culture-negative and positive samples (p = 0.23). Conclusions The paired analysis demonstrated a strong concordance between culture positivity and suppurative inflammation within the same sample. Combining microbiology and histology may help identify patients at increased risk of revision, although larger studies are needed. The present study indicates that when a viable bacterium induces an inflammatory response, there is a greater risk of non-osteoclast-based tissue breakdown, destruction, or liquefaction, and thus a greater risk of local bacterial dispersion or hiding, which may facilitate mis-removal during debridement and antibiotic therapy, leading to increased risk of relapse.