{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:44:03Z","timestamp":1773881043580,"version":"3.50.1"},"reference-count":35,"publisher":"International Union Against Tuberculosis and Lung Disease","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJTLD Open"],"accepted":{"date-parts":[[2025,8,18]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Lack of quantitative and reproducible treatment response biomarkers is slowing the development of better therapy regimens for pulmonary\n                      <jats:italic>Mycobacterium avium<\/jats:italic>\n                      complex (P-MAC) disease. We hypothesised that steeper bacterial elimination rate slopes (BERSs) would be associated with faster mycobacterial cure and more favourable outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We retrospectively compared serial sputum culture (SSC) trajectories and outcomes of 29 P-MAC patients, of whom 26\/29 (90%) had concurrent HIV infection, treated with guideline-based therapy (GBT) versus non-GBT regimens at a tertiary hospital in Gauteng province of South Africa between 2013 and 2017. We used \u2018current value\u2019 parameterisation of joint models with BERSs as longitudinal biomarkers for the composite outcomes of time-to-death or therapy failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Overall, initial bacterial burden and BERS trajectories were heterogeneous. BERSs ranged from \u22120.034 to 0.013 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL per day. BERSs were significantly steeper in the 18 (62%) censored survivors, with median (interquartile range) \u22120.011 (\u22120.021, \u22120.008), versus 0.002 (\u22120.008, 0.003) in 11 (38%) non-survivors or therapy failure. In multivariate analyses, one log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL\/day decline was associated with an 88% reduction in the hazard for death or therapy failure (95% confidence intervals, 0.04, 0.34).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>BERSs from sputum are potential P-MAC treatment response biomarkers, which should be evaluated further in larger prospective studies of people with and without HIV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5588\/ijtldopen.25.0313","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:54:56Z","timestamp":1771926896000},"page":"97-104","source":"Crossref","is-referenced-by-count":0,"title":["<i>Mycobacterium avium<\/i>\n                    complex (MAC) elimination slopes from sputum are potential treatment response biomarkers in patients with HIV and pulmonary MAC"],"prefix":"10.5588","volume":"3","author":[{"given":"J.G.","family":"Pasipanodya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Nqwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.N.","family":"Wanjalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.S.","family":"Wallis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.E.","family":"Dooley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3554","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"2026031812064705000_3.2.97.1","doi-asserted-by":"crossref","first-page":"1504449","DOI":"10.3389\/fmicb.2024.1504449","article-title":"Editorial: recent advancements in mycobacterial diseases research","volume":"15","author":"Johansen","year":"2024","journal-title":"Front Microbiol"},{"key":"2026031812064705000_3.2.97.2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx311"},{"issue":"1","key":"2026031812064705000_3.2.97.3","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/s42003-021-02184-0","article-title":"Bacterial load slopes represent biomarkers of tuberculosis therapy success, failure, and relapse","volume":"4","author":"Magombedze","year":"2021","journal-title":"Commun Biol"},{"key":"2026031812064705000_3.2.97.4","doi-asserted-by":"publisher","DOI":"10.1101\/2022.03.13.484155"},{"issue":"3","key":"2026031812064705000_3.2.97.5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1164\/rccm.202311-2004OC","article-title":"High-dose isoniazid lacks EARLY bactericidal activity against isoniazid-resistant tuberculosis mediated by katG mutations: a randomized phase II clinical trial","volume":"210","author":"Gausi","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"key":"2026031812064705000_3.2.97.6","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00925-2015"},{"key":"2026031812064705000_3.2.97.7","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.25"},{"key":"2026031812064705000_3.2.97.8","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00170-2018"},{"key":"2026031812064705000_3.2.97.9","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S2213-2600(15)00058-2","article-title":"Sputum culture conversion as a tuberculosis biomarker: a glass half empty or half full?","volume":"3","author":"Wallis","year":"2015","journal-title":"Lancet Respir Med"},{"key":"2026031812064705000_3.2.97.10","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"},{"key":"2026031812064705000_3.2.97.11","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201605-344BC"},{"key":"2026031812064705000_3.2.97.12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-571ST"},{"key":"2026031812064705000_3.2.97.13","doi-asserted-by":"crossref","unstructured":"Kalbfleisch J , Prentice R . 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