title: Simultaneous staining of sputum smears for acid-fast and lipid-containing Myobacterium tuberculosis can enhance the clinical evaluation of antituberculosis treatments.
abstract: Dormant, slow-growing, antibiotic-tolerant Mycobacterium tuberculosis undermine the shortening of tuberculosis treatment to less than 6 months and are thought to be characterised by intracellular lipid bodies. Antibiotic effects on such persisting bacilli escape evaluation as they cannot be readily cultured. We identified cells containing lipid bodies in sputum smears from 86 newly diagnosed pulmonary tuberculosis patients and monitored these cells daily in 42 patients over the first 14 days of treatment with rifampicin, the experimental compound SQ-109, or both agents combined. Counts of Nile-Red-positive lipid-body containing cells were correlated with those of Auramine-O-positive cells and colony forming units of viable Mycobacterium tuberculosis on agar plates. Rifampicin but not SQ-109 significantly reduced colony forming units but all treatments distinctively and significantly changed the proportions of lipid body-containing bacilli and viable Mycobacterium tuberculosis. Monitoring lipid-body containing bacilli in sputum during treatment with experimental antituberculosis regimens may identify putative treatment-shortening regimens.
authors: 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.
authors: Xavier A
authors: XA
authors: Kayigire
authors: 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.
authors: Sven O
authors: SO
authors: Friedrich
authors: Department of Statistics, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa.
authors: Lize
authors: L
authors: van der Merwe
authors: Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors: Peter R
authors: PR
authors: Donald
authors: 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. Electronic address: ahd@sun.ac.za.
authors: Andreas H
authors: AH
authors: Diacon
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D001576:Benzophenoneidum; D015169:Colony Count, Microbial; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005029:Ethylenediamines / Q000627:therapeutic use*; D005456:Fluorescent Dyes; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010078:Oxazines; D011237:Predictive Value of Tests; D012293:Rifampin / Q000627:therapeutic use*; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D005029:Ethylenediamines; D005456:Fluorescent Dyes; C506841:N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine; D010078:Oxazines; D001576:Benzophenoneidum; C044808:nile red; D000218:Adamantane; D012293:Rifampin
keywords: Dormancy; Fluorescence microscopy; Mycobacterium tuberculosis; Rifampicin