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Background: Musculoskeletal infections (MSKIs) are a major cause of morbidity in the pediatric population and account for nearly 1 in every 10 consultations with a pediatric orthopaedic provider at a tertiary care center. To prevent or deescalate the risk of adverse medical and musculoskeletal outcomes, timely medical intervention in the form of antibiotics and potential surgical debridement is required. While there have been numerous studies indicating the value of laboratory testing during the initial workup of a child with MSKI, few studies to date have examined the utility of longitudinal assessment of laboratory measures in the acute setting to monitor the efficacy of antibiotic therapy and/or surgical intervention. The purpose of this investigation was to retrospectively determine whether measuring changes in the inflammatory response could indicate the need for escalated care. Specifically, this study examined the hypothesis that serial measurements of C-reactive protein (CRP), immediately preoperatively and 2 days after surgical debridement, could predict the need for medical (change in antibiotics) or surgical (additional debridement) escalation., Methods: Retrospective review of pediatric patients undergoing operative debridement for the treatment of MSKI between September 2009 and December 2015 from whom laboratory data (CRP) was obtained preoperatively and at postoperative day (POD) 2. Patient demographics, the need for escalated care, and patient outcomes were evaluated., Results: Across 135 pediatric patients, preoperative CRP values >90 mg/L and a positive change in CRP at POD2 effectively predicted the need for escalation of care after initial surgical debridement (Area under the Receiver Operator Curve: 0.883). For each 10-unit increase in preoperative CRP or postoperative change in CRP, there was a 21% or 22% increased risk of needing escalated care, respectively. Stratification by preoperative CRP >90 mg/L and change in CRP postoperatively likewise correlated with increased rates of disseminated disease, percent tissue culture positivity, length of stay, and rate of adverse outcomes., Conclusions: This study demonstrates the utility of serial CRP to assess the need for escalated care in patients being treated for MSKI. As serial CRP measurements become standard of practice in the acute setting, future prospective studies are needed to optimize the timing of CRP reassessment during inpatient hospitalization to prognosticate patient outcomes, weighing both improvements of patient care and clinical burden., Level of Evidence: Level III-retrospective comparative study., Competing Interests: J.G.S. is a member of the education advisory board at OrthoPediatrics, serves as a board member of Pediatric Society of North America (POSNA) and research support from IONIS Pharmaceuticals. The remaining authors report conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)