Isothermal Microcalorimetry Improves the Time to Diagnosis of Fracture-related Infection Compared With Conventional Tissue Cultures

A consensus definition recently was formulated for fracture-related infection, which centered on confirmatory criteria including conventional cultures that take time to finalize and have a 10% to 20% false-negative rate. During this time, patients are often on broad-spectrum antibiotics and may remain hospitalized until cultures are finalized to adjust antibiotic regimens. (1) What is the diagnostic accuracy of isothermal microcalorimetry, and how does its accuracy compare with that of conventional cultures? (2) Does isothermal microcalorimetry decrease time to detection (or diagnosis) of fracture-related infection compared with conventional cultures? (3) Does isothermal microcalorimetry have a diagnostic accuracy or time advantage over conventional cultures in patients on chronic suppressive antibiotics? Between July 2020 and August 2021, we treated 310 patients with concerns for infection after prior fracture repair surgery. Of those, we considered all patients older than 18 years of age with fixation hardware in place at the time of presentation as potentially eligible. All included patients returned to the operating room with cultures obtained and assessed by both isothermal microcalorimetry and conventional cultures, and all were diagnosed using the consensus criteria for fracture-related infection. Based on that, 81% (250 of 310) of patients were eligible; a further 51% (157 of 310) were excluded because of the following reasons: the capacity of the isothermal microcalorimetry instrument limited the throughput on that day (34% [106 of 310]), they had only swab cultures obtained in surgery (15% [46 of 310]), or they had less than 3 months follow-up after surgery for infectious concerns (2% [5 of 310]), leaving 30% (93 of 310) of the originally identified patients for analysis. We obtained two to five cultures from each patient during surgery, which were sent to our clinical microbiology laboratory for standard processing (conventional cultures). This included homogenization of each tissue sample individually and culturing for aerobic, anaerobic, acid-fast bacilli, and fungal culturing. The remaining homogenate from each sample was then taken to our orthopaedic research laboratory, resuspended in growth media, and analyzed by isothermal microcalorimetry for a minimum of 24 hours. Aerobic and anaerobic cultures were maintained for 5 days and 14 days, respectively. Overall, there were 93 patients (59 males), with a mean age of 43 ± 14 years and a mean BM