Diagnostic test accuracy of serum procalcitonin compared with C-reactive protein for bone and joint infection in children and adolescents: a systematic review and meta-analysis

OBJECTIVE: The objective of this review was to synthesize the best available evidence for the diagnostic test accuracy of serum procalcitonin compared with serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalized children and adolescents. INTRODUCTION: Measurement of serum C-reactive protein remains a routine investigation for the diagnosis of osteoarticular infection in children and adolescents. Measurement of serum procalcitonin has been shown to outperform C-reactive protein in adults with osteomyelitis and septic arthritis. Before procalcitonin can be considered as a potential replacement or add-on test in children and adolescents, a systematic review and meta-analysis targeting this population should be conducted. INCLUSION CRITERIA: Original studies reporting the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents between one month and 18 years of age admitted to hospital with suspected osteoarticular infection were included. Studies must have compared the index test to at least one reference test. Reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood, bone biopsy, or joint fluid aspirate in combination with at least two of the following: i) purulent material from sterile site, ii) positive radiological findings consistent with osteoarticular infection, and ii) symptoms and signs consistent with osteomyelitis and/or septic arthritis. METHODS: The JBI methodology for systematic reviews of diagnostic test accuracy was followed. Information was sourced from four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) and four gray literature sources (MedNar, OpenGrey, Google Scholar, and ProQuest Dissertations and Theses). Only studies published in English were considered. The methodological quality of selected studies was formally evaluated, sensitivity and specificity data were extracted, and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and to generate a hierarchical summary receiver operating characteristic (HSROC) curve with global measures of test accuracy performance, such as likelihood ratio and diagnostic odds ratio. A narrative was provided where meta-analysis was not appropriate. RESULTS: Eight studies were included in the review. Four of these studies used a common C-reactive protein test threshold of 20 mg/L. At this threshold, the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity was 0.9 (0.83-0.94). Using a hierarchical summary receiver operating characteristic model from six studies, the diagnostic odds ratio for C-reactive protein was estimated to be 39.4 (14.8-104.9) with a positive likelihood ratio 5.3 (2.3-11.9) and a negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy of procalcitonin. CONCLUSION: Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in hospitalized children and adolescents with suspected osteomyelitis or septic arthritis. More evidence is needed before incorporating procalcitonin routinely into clinicians' diagnostic test strategy. Improvements with the design, quality, and reporting of procalcitonin diagnostic test assays in children and adolescents with osteoarticular infection is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140276.