Age and CRP Associated with Improved Tissue Pathogen Identification in Children with Blood Culture Negative Osteomyelitis: Results from the CORTICES Multicenter Database

Background: Acute hematogenous osteomyelitis (AHO) is a relatively common condition in children, and identifying the offending pathogen with blood or tissue cultures aids in diagnosis and medical management while reducing treatment failure. Recent 2021 AHO clinical practice guidelines from the Pediatric Infectious Disease Society recommend obtaining routine tissue cultures, particularly in cases with negative blood cultures. The purpose of this study was to identify variables associated with positive tissue cultures when blood cultures are negative. Methods: Children with AHO from 18 pediatric medical centers throughout the United States through the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study were evaluated for predictors of positive tissue cultures when blood cultures were negative. Cutoffs of predictors were determined with associated sensitivity and specificity. Results: One thousand three children with AHO were included, and in 688/1003 (68.6%) patients, both blood cultures and tissue cultures were obtained. In patients with negative blood cultures (n=385), tissue was positive in 267/385 (69.4%). In multivariate analysis, age (P<0.001) and C-reactive protein (CRP) (P=0.004) were independent predictors. With age >3.1 years and CRP >4.1 mg/dL as factors, the sensitivity of obtaining a positive tissue culture when blood cultures were negative was 87.3% (80.9-92.2%) compared with 7.1% (4.4-10.9%) if neither of these factors was present. There was a lower ratio of methicillin-resistant Staphylococcus aureus in blood culture-negative patients who had a positive tissue culture 48/188 (25.5%), compared with patients who had both positive blood and tissue cultures 108/220 (49.1%). Conclusion: AHO patients with CRP ≤ 4.1 mg/dL and age under 3.1 years are unlikely to have clinical value from tissue biopsy that exceeds the morbidity associated with this intervention. In patients with CRP > 4.1 mg/dL and age over 3.1 years, obtaining a tissue specimen may add value; however, it is important to note that effective empiric antibiotic coverage may limit the utility of positive tissue cultures in AHO. Level of Evidence: Level III - Retrospective comparative study.