Next-generation sequencing for diagnosis of infection: is more sensitive really better?

Background: The utility of next-generation sequencing (NGS) in differentiating between active infection and contaminant or baseline flora remains unclear. The purpose of this study is to compare NGS with culture-based methods in primary shoulder arthroplasty. Methods: A prospective series of primary shoulder arthroplasty patients with no history of infection or antibiotic use within 60 days of surgery was enrolled. All patients received standard perioperative antibiotics. After skin incision, a 10 × 3-mm sample of the medial skin edge was excised. A 2 × 2-cm synovial tissue biopsy was taken from the rotator interval after subscapularis takedown. Each sample set was halved and sent for NGS and standard cultures. Results: Samples from 25 patients were analyzed. Standard aerobic/anaerobic cultures were positive in 10 skin samples (40%, 95% confidence interval [CI] 20%-60%) and 3 deep tissue samples (12%, 90% CI 1%-23%]). NGS detected ≥1 bacterial species in 17 of the skin samples (68%, 95% CI 49%-87%) and 7 deep tissue samples (28%, 95% CI 9%-47%). There was a significant difference (P < .03) in the mean number of bacterial species detected with NGS between the positive standard culture (1.6 species) and the negative standard culture groups (5.7 species). Conclusion: NGS identified bacteria at higher rates in skin and deep tissue samples than standard culture did in native, uninfected patients undergoing primary procedures. Further research is needed to determine which NGS results are clinically relevant and which are false positives before NGS can be reliably used in orthopedic cases.