Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania

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dc.contributor.authorMbelele, P.M.
dc.contributor.authorMpolya, E.A.
dc.contributor.authorSauli, E.
dc.contributor.authorMtafya, B.
dc.contributor.authorNtinginya, N.E.
dc.contributor.authorAddo, K.K.
dc.contributor.authorKreppel, K.
dc.contributor.authorMfinanga, S.
dc.contributor.authorPhillips, P.P.J.
dc.contributor.authorGillespie, S.H.
dc.contributor.authorHeysell, S.K.
dc.contributor.authorSabiiti, W.
dc.contributor.authorMpagama, S.G.
dc.date.accessioned2021-04-29T16:07:55Z
dc.date.available2021-04-29T16:07:55Z
dc.date.issued2021
dc.descriptionResearch Articleen_US
dc.description.abstractRifampin 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.en_US
dc.identifier.otherhttps://doi.org/10.1128/JCM .02927-20.
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/36287
dc.language.isoenen_US
dc.publisherJournal of Clinical Microbiologyen_US
dc.subjectKibong'otoen_US
dc.subjectTanzaniaen_US
dc.subjectMDR-TB treatment regimensen_US
dc.subjectmolecular bacterial load assayen_US
dc.subjectmultidrug-resistant TBen_US
dc.subjectmycobactericidal effectsen_US
dc.subjectMycobacterium tuberculosisen_US
dc.subjectall-oral bedaquiline regimenen_US
dc.subjectinjectable aminoglycoside regimenen_US
dc.titleMycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzaniaen_US
dc.typeArticleen_US

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