Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate of <i>Mycobacterium tuberculosis</i> in patients with multidrug-resistant tuberculosis in Tanzania

Abstract Background Rifampin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has transitioned to injectable-free regimens. We tested whether M. tuberculosis ( Mtb ) elimination rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB antibiotic regimen. Methods Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at day 0, 3, 7, 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable Mtb 16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL). Mtb elimination rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. Results Among 37 patients with a total of 296 serial sputa; 7 patients received rifampin/isoniazid/pyrazinamide/ethambutol (RHZE), 8 an all-oral bedaquiline-based regimen, 9 an injectable and bedaquiline-containing regimen, and 13 an injectable-containing but bedaquiline-free regimen. The overall mean daily Mtb elimination was −0.24 [95% Confidence-Interval (CI); −0.39 to −0.08)] log 10 eCFU/mL, and it varied with treatment-regimen (p &lt; 0.001). Compared to the adjusted Mtb elimination of −0.17 (95% CI; −0.23 to −0.12) for the injectable-containing but bedaquiline-free reference regimen, the elimination rates were −0.62 (95% CI; −1.05 to −0.20) log 10 eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), −0.35 (95% CI; −0.65 to −0.13) log 10 eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and −0.29 (95% CI; −0.78 to +0.22) log 10 eCFU/mL for RHZE (p = 0.332) Conclusion TB-MBLA distinguished Mtb elimination rates in sputa from patients receiving different treatment regimens, suggesting a reliable monitoring tool for RR/MDR-TB, that does not require mycobacterial culture.