Acquisition of Rifampin Resistance in Pulmonary Tuberculosis.
Mycobacterium tuberculosisstrains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loads, including mutation frequencies, were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be RIF resistant after 30 days of monotherapy. This indicates that temporal and spatial windows of RIF monotherapy due to uneven drug distribution within lung lesions could contribute to the acquisition of resistance to RIF.
Division of Molecular Biology and Human Genetics, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.|Task Applied Science, Bellville, Cape Town, South Africa.
Xavier A
XA
Kayigire
Division of Medical Physiology, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.|Task Applied Science, Bellville, Cape Town, South Africa.
Sven O
SO
Friedrich
Task Applied Science, Bellville, Cape Town, South Africa.
Lize
L
van der Merwe
Division of Medical Physiology, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa ahd@sun.ac.za.|Task Applied Science, Bellville, Cape Town, South Africa.
Andreas H
AH
Diacon
D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D058491:Bacterial Load / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015169:Colony Count, Microbial; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015233:Models, Statistical; D059645:Mutation Rate; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin
resistance; rifampin; treatment; tuberculosis