Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Clinical Microbiology
Abstract
Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has
largely transitioned to regimens free of the injectable aminoglycoside component,
despite the drug class’ purported bactericidal activity early in treatment. We tested
whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular
bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDRTB
regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive
TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment.
TB-MBLA was used to quantify viable M. tuberculosis 16S rRNA in sputum for estimation
of colony forming units per ml (eCFU/ml). M. tuberculosis killing rates were compared
among regimens using nonlinear-mixed-effects modeling of repeated measures.
Thirty-seven patients produced 296 serial sputa and received treatment as follows:
13 patients received an injectable bedaquiline-free reference regimen, 9 received an
injectable bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen,
and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/
pyrazinamide/ethambutol (RHZE). Compared to the adjusted M. tuberculosis killing of
20.17 (95% confidence interval [CI] 20.23 to 20.12) for the injectable bedaquiline-free
reference regimen, the killing rates were 20.62 (95% CI 21.05 to 20.20) log10 eCFU/ml
for the injectable bedaquiline-containing regimen (P=0.019), 20.35 (95% CI 20.65 to
20.13) log10 eCFU/ml for the all-oral bedaquiline-based regimen (P=0.054), and 20.29
(95% CI 20.78 to 10.22) log10 eCFU/ml for the RHZE regimen (P=0.332). Thus, M. tuberculosis
killing rates from sputa were higher among patients who received bedaquiline but
were further improved with the addition of an injectable aminoglycoside.
Description
Research Article
Keywords
Kibong'oto, Tanzania, MDR-TB treatment regimens, molecular bacterial load assay, multidrug-resistant TB, mycobactericidal effects, Mycobacterium tuberculosis, all-oral bedaquiline regimen, injectable aminoglycoside regimen