Neutrophil CD64 index for diagnosing and tracking treatment response across the mycobacterial infection spectrum: a retrospective two-cohort study

Abstract

The neutrophil CD64 (nCD64) index has emerged as a promising biomarker for infection detection, but its evaluation within the mycobacterial infection spectrum remains limited. Here, we evaluated the diagnostic and treatment response performance of the nCD64 index in the active tuberculosis (ATB)—including pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (ePTB), and non-tuberculous mycobacterial (NTM) disease, and determined whether it adds value beyond standard inflammatory indicators. We measured the nCD64 index in a cross-sectional cohort comprising 248 participants across five groups: ATB, latent tuberculosis infection (LTBI), NTM, bacterial pulmonary infection (PI) and healthy donors (HD). Patients with ATB and NTM had not received anti-mycobacterial treatment at the time of enrollment. Diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis, and incremental value beyond white blood cell (WBC) count and C-reactive protein (CRP) was evaluated by comparing an area under the curve (AUC) with and without nCD64 index. In a separate longitudinal cohort of 244 participants, nCD64 index was measured at baseline and months 1–3 of anti-mycobacterial therapy, and longitudinal trajectories were compared between treatment-naive and retreatment patients using a linear mixed-effects (LME) model. nCD64 index was markedly elevated in ATB compared to all other groups (all p  < 0.001). It discriminated ATB from LTBI with an AUC of 0.739 and PTB from NTM with an AUC of 0.744. Addition of nCD64 index to WBC count significantly improved AUC in four diagnostic comparisons with gains of 0.12 to 0.34, most markedly for PTB versus PI. nCD64 index was significantly higher in PTB than NTM ( p  < 0.001) with limited stratification by clinical features. In the longitudinal cohort, nCD64 index declined progressively from month 1 in both PTB and NTM patients and remained lower through month 3. Treatment-naive patients exhibited significantly steeper decline trajectories than retreatment patients (PTB p  < 0.001, NTM p  = 0.004). The nCD64 index discriminates ATB from LTBI and NTM, adds diagnostic value beyond routine inflammatory markers, and tracks serial changes during treatment in both ATB and NTM. Treatment-naive patients showed more pronounced decline trajectories, supporting particular utility of the nCD64 index for tracking initial treatment response. It warrants further evaluation as a complementary biomarker in the clinical management of mycobacterial infections.