Comparative evaluation of the Xpert MTB/XDR and FluoroType XDR assays for detecting fluoroquinolone resistance in multidrug-resistant tuberculosis clinical isolates

Background: Accurate detection of fluoroquinolone (FLQ) resistance in multidrug-resistant tuberculosis (MDR-TB) is essential for effective treatment. Aim: To compare Xpert MTB/XDR and FluoroType XDR for detecting FLQ resistance in MDR-TB. Setting: National Health Laboratory Service diagnostic laboratory, Polokwane, South Africa. Methods: Seventy-eight MDR-TB isolates collected from January 2024 to July 2024 were tested using Xpert MTB/XDR, FluoroType XDR and GenoType MTBDRsl line probe assay (LPA) as the reference standard. Whole-genome sequencing (WGS) data from 35 isolates were used to resolve discordant results. Diagnostic accuracy and agreement were assessed using sensitivity, specificity and Cohen’s kappa. Results: Xpert MTB/XDR showed 97.7% sensitivity (95% confidence interval [CI]: 87.9–99.8) and 100.0% specificity (95% CI: 89.7–100.0). FluoroType XDR showed 100.0% sensitivity (95% CI: 90.6–100.0) and 97.2% specificity (95% CI: 85.5–99.9), with five indeterminate results. Compared directly with Xpert, FluoroType showed 94.9% sensitivity and 100.0% specificity. Agreement was strong (κ = 0.95; 95% CI: 0.88–1.00). WGS resolved two discordant cases: one resistant isolate with a *gyrA* Asp94Gly mutation and one susceptible isolate without resistance-associated mutations. Conclusion: Both assays performed well for FLQ resistance detection. FluoroType XDR showed higher sensitivity but more indeterminate results. Strong assay agreement and WGS resolution of discordances support their use in MDR-TB diagnostics. Contribution: This study demonstrates strong concordance between Xpert MTB/XDR and FluoroType XDR for FLQ resistance detection and highlights the value of WGS in resolving discordant results.