Multiplex Polymerase Chain Reaction and Microcalorimetry in Synovial Fluid: Can Pathogen-based Detection Assays Improve the Diagnosis of Septic Arthritis?

Abstract

To prospectively evaluate automated multiplex PCR and isothermal microcalorimetry tests for rapid and accurate diagnosis of septic arthritis. Patients with acute arthritis were prospectively included from October 2014 to September 2015. In synovial fluid (SF), leukocyte count and differential, culture, PCR, and microcalorimetry were determined. Septic arthritis was diagnosed by positive SF culture or (1) local clinical signs and symptoms, (2) increased SF leukocyte count, and (3) exclusion of noninfectious causes of inflammatory arthropathy. The performance of individual tests was compared with McNemar's test. Among 57 patients, 22 (39%) were diagnosed with septic arthritis. SF culture grew a pathogen in 10 patients (46%), PCR was positive in 5 (23%), and microcalorimetry in 10 (46%). Compared to SF culture, 49 concordant pairs were found for both methods (PCR and microcalorimetry; 86% agreement). In SF, PCR failed to detect Staphylococcus aureus (2 patients), Streptococcus pneumoniae (1 patient), Streptococcus dysgalactiae (1 patient), and Clostridium clostridioforme (1 patient). Microcalorimetry failed to detect S. dysgalactiae (1 patient), Streptococcus agalactiae (1 patient), and C. clostridioforme (1 patient). No statistical differences between the performance of SF culture, and PCR and microcalorimetry, respectively, were found. The processing time for PCR was 5 h and for microcalorimetry a median of 8.8 h (range, 2.3-64 h), whereas cultures required a median of 4.5 days (range, 3-14 days). Performance of SF PCR was inferior while microcalorimetry was similar to culture but provided results considerably faster. [Clinical trial registration number (https://www.clinicaltrials.gov): NCT02530229].