The diagnositic test accuracy of serum procalcitonin compared to C-reactive protein for bone and joint infection in children and adolescents: A Systematic review and Meta-analysis

Abstract

Objective: To synthesise the best available evidence for the diagnostic test accuracy of measurement of serum procalcitonin compared to serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalised 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 additional test in children and adolescents, a systematic review and meta-analysis targeting this population is needed. Inclusion criteria: Original studies reporting on the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents aged between one month and 18 years admitted to hospital with suspected osteoarticular infection were included, compared to at least one reference test. The reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood and/or bone biopsy and/or joint fluid aspirate and/or at least two of the following: 1) purulent material from sterile site; 2) positive radiological findings consistent with osteoarticular infection; 3) symptoms and signs consistent with osteomyelitis and/or septic arthritis. Methods: JBI methodology for systematic reviews of diagnostic test accuracy was employed. Information was sourced from four databases; MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science and four grey literature sources; Mednar, OpenGrey, Google scholar and ProQuest Dissertations and Thesis. Only studies published in English were considered. The methodological quality of selected studies was formally evaluated and sensitivity and specificity data were extracted and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and generate a hierarchial summary receiver operating characteristic curve (HSROC) with global measures of test accuracy performance including likelihood ratio and diagnostic odds ratio. A narrative summary was provided where meta-analysis was not feasible. Results: Eight out of 3086 studies were included in the final analysis. Four of these studies used a common CRP test threshold of 20mg/L for septic arthritis cases only. At this threshold the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity 0.9 (0.83-0.94). Using a HSROC model from six studies including all osteoarticular infections, 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 negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy performance of procalcitonin using meta-analysis. Conclusion: We have synthesised the best available evidence to evaluate the diagnostic test accuracy of serum measurement of procalcitonin and C-reactive protein in children and adolescents with suspected osteomyelitis and septic arthritis. Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in this setting and await more evidence before incorporating procalcitonin routinely into their diagnostic test strategy for this specific setting.