The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif

Objectives

Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods

The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Results

Mycobacterium tuberculosis culture conversion was used as the read-out for treatment responses. The MBLA was most concordant during the early phase of treatment, detecting changes in bacterial load with similar accuracy to microscopy and outperforming Xpert. When considering all timepoints, concordance with MGIT results was 72.1% for MBLA, 57.4% for Xpert and 76.7% for microscopy. The AUC for culture conversion was higher for MBLA (0.88, CI 0.84–0.95) than for Xpert (0.78, CI 0.72–0.85) and microscopy (0.77, CI 0.71–0.83).

Conclusions

MBLA was superior in the early identification of successful culture conversion compared to microscopy and Xpert and could be a useful biomarker to evaluate novel entities in Phase IIA early-bactericidal-activity drug trials regardless of the degree of M. tuberculosis drug resistance.