Metagenomic next-generation sequencing in tuberculous periprosthetic joint infection: pathogen-detection yield and clinical characteristics compared with common bacterial PJI

Objective To compare the pathogen-detection yield of metagenomic next-generation sequencing (mNGS) and conventional culture in tuberculous periprosthetic joint infection (TB-PJI) and common bacterial PJI (CB-PJI), and to characterize clinical differences and exploratory associations with TB-PJI. Methods A retrospective cohort included 197 patients with periprosthetic joint infection treated between January 2016 and June 2024 who underwent both conventional culture and mNGS during the same diagnostic or surgical episode. Patients were classified as CB-PJI (n=178) or TB-PJI (n=19). Paired pathogen-detection rates were compared using McNemar’s test. Exploratory multivariable associations with TB-PJI were assessed using Firth penalized logistic regression with the Charlson Comorbidity Index (CCI) modeled continuously. Results In CB-PJI, mNGS showed a higher pathogen-detection rate than conventional bacterial culture (94.4% vs. 78.1%, P<0.001). In TB-PJI, Mycobacterium tuberculosis complex (MTBC) was detected by mNGS in 17/19 cases (89.5%) and recovered by mycobacterial culture in 5/19 cases (26.3%; P<0.001); 12/19 cases were mNGS-positive/mycobacterial-culture-negative. In the primary exploratory Firth model, each 1-point increase in CCI was associated with higher odds of TB-PJI (aOR=2.39, 95% CI: 1.51-4.10, P<0.001), whereas each 10% increase in SF PMN% was associated with lower odds (aOR=0.722, 95% CI: 0.564-0.917, P = 0.009); BMI was not statistically significant. Drug-related complications were more frequent in TB-PJI (42.1% vs. 11.8%, P = 0.002), while the 2-year infection recurrence rate did not differ significantly (15.8% vs. 7.9%, P = 0.216). Conclusion In this selected retrospective cohort, mNGS provided a higher pathogen-detection yield than conventional culture, particularly for TB-PJI. Higher CCI and lower SF PMN% were exploratory clinical associations with TB-PJI and should not be interpreted as validated diagnostic thresholds. mNGS should be considered an adjunct to mycobacterial culture, molecular testing, and histopathology rather than a stand-alone diagnostic test.