Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania
| Autor: | Sayoki Mfinanga, Elingarami Sauli, Stephen H. Gillespie, Wilber Sabiiti, Katharina S. Kreppel, Nyanda E. Ntinginya, Scott K. Heysell, Emmanuel A. Mpolya, Kennedy Kwasi Addo, Peter M. Mbelele, Bariki Mtafya, Stellah G. Mpagama, Patrick P. J. Phillips |
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| Přispěvatelé: | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Centre for Biophotonics, University of St Andrews. Infection and Global Health Division, University of St Andrews. Global Health Implementation Group, University of St Andrews. Gillespie Group, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. School of Medicine, Turenne, Christine Y |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Antitubercular Agents Mycobacterial effects Medical and Health Sciences Tanzania chemistry.chemical_compound 0302 clinical medicine RA0421 RNA Ribosomal 16S RA0421 Public health. Hygiene. Preventive Medicine Tuberculosis Multidrug-Resistant 030212 general & internal medicine Diarylquinolines biology Isoniazid Aminoglycoside QR Microbiology Multidrug-Resistant Biological Sciences multidrug-resistant TB mycobactericidal effects Infectious Diseases molecular bacterial load assay 6.1 Pharmaceuticals Infection Kibong'oto Molecular bacterial load assay medicine.drug Microbiology (medical) 16S RM medicine.medical_specialty Tuberculosis Multidrug-resistant TB 030106 microbiology NDAS Microbiology Mycobacterium tuberculosis 03 medical and health sciences Rare Diseases SDG 3 - Good Health and Well-being Internal medicine medicine Humans Ethambutol Ribosomal all-oral bedaquiline regimen Agricultural and Veterinary Sciences All-oral bedaquiline regimen Injectable aminoglycoside regimen business.industry Prevention Evaluation of treatments and therapeutic interventions Mycobacteriology and Aerobic Actinomycetes Pyrazinamide biology.organism_classification medicine.disease Bacterial Load RM Therapeutics. Pharmacology QR Regimen Emerging Infectious Diseases Orphan Drug Good Health and Well Being chemistry RNA Antimicrobial Resistance Bedaquiline injectable aminoglycoside regimen business MDR-TB treatment regimens |
| Zdroj: | Journal of Clinical Microbiology Journal of clinical microbiology, vol 59, iss 4 |
| ISSN: | 1098-660X 0095-1137 |
| DOI: | 10.1128/jcm.02927-20 |
| Popis: | 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 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/MDR-TB 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 −0.17 (95% confidence interval [CI] −0.23 to −0.12) for the injectable bedaquiline-free reference regimen, the killing rates were −0.62 (95% CI −1.05 to −0.20) log10 eCFU/ml for the injectable bedaquiline-containing regimen (P = 0.019), −0.35 (95% CI −0.65 to −0.13) log10 eCFU/ml for the all-oral bedaquiline-based regimen (P = 0.054), and −0.29 (95% CI −0.78 to +0.22) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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