@article{Barr2022,
abstract = {Background Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. Methods We established a microscopy method for direct visualisation ofM. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert{\`{O}} MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients pre- dicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. Findings M. tuberculosis was detected in 27 of28 recruited participants; 25 (89{\%}) by blood Xpert-ultra, 22 (79{\%}) by DMN-Tre microscopy, and 21 (75{\%}) by Myco/F lytic blood culture. Eight (29{\%}) participants died by 12-week follow- up. In a combined pharmacodynamic model, predicted probabilities ofnegative DMN-Tre microscopy, blood Xpert- ultra, or blood culture after 72 h treatment were 0¢64, 0¢27, and 0¢94, respectively, in those who survived, compared with 0¢23, 0¢06, and 0¢71 in those who died (posterior probability ofslower clearance ofMTBBSI in those that died {\textgreater}0¢99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolo- nies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0¢13 log- µm/day; 95{\%}CrI 0¢10?0¢16). Interpretation Pharmacodynamics ofMTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert- ultra and culture. This could facilitate interventional trials in severe HIV-associated TB.},
author = {Barr, David A. and Schutz, Charlotte and Balfour, Avuyonke and Shey, Muki and Kamariza, Mireille and Bertozzi, Carolyn R and de Wet, Timothy J and Dinkele, Ryan and Ward, Amy and Haigh, Kathryn A and Kanyik, Jean-Paul and Mizrahi, Valerie and Nicol, Mark P and Wilkinson, Robert J and Lalloo, David G and Warner, Digby F and Meintjes, Graeme A and Davies, Gerry},
doi = {10.1016/J.EBIOM.2022.103949},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barr et al. - 2022 - Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis.pdf:pdf},
issn = {2352-3964},
journal = {eBioMedicine},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {apr},
pages = {103949},
pmid = {35325781},
publisher = {Elsevier},
title = {{Serial measurement of \textit{M. tuberculosis} in blood from critically-ill patients with HIV-associated tuberculosis}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396422001335},
volume = {78},
year = {2022}
}

{"_id":"EftdE8JuE9iP9eZYo","bibbaseid":"barr-schutz-balfour-shey-kamariza-bertozzi-dewet-dinkele-etal-serialmeasurementofimtuberculosisiinbloodfromcriticallyillpatientswithhivassociatedtuberculosis-2022","author_short":["Barr, D. A.","Schutz, C.","Balfour, A.","Shey, M.","Kamariza, M.","Bertozzi, C. R","de Wet, T. J","Dinkele, R.","Ward, A.","Haigh, K. A","Kanyik, J.","Mizrahi, V.","Nicol, M. P","Wilkinson, R. J","Lalloo, D. G","Warner, D. F","Meintjes, G. A","Davies, G."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. Methods We established a microscopy method for direct visualisation ofM. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpertÒ MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients pre- dicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. Findings M. tuberculosis was detected in 27 of28 recruited participants; 25 (89%) by blood Xpert-ultra, 22 (79%) by DMN-Tre microscopy, and 21 (75%) by Myco/F lytic blood culture. Eight (29%) participants died by 12-week follow- up. In a combined pharmacodynamic model, predicted probabilities ofnegative DMN-Tre microscopy, blood Xpert- ultra, or blood culture after 72 h treatment were 0¢64, 0¢27, and 0¢94, respectively, in those who survived, compared with 0¢23, 0¢06, and 0¢71 in those who died (posterior probability ofslower clearance ofMTBBSI in those that died \\textgreater0¢99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolo- nies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0¢13 log- µm/day; 95%CrI 0¢10?0¢16). Interpretation Pharmacodynamics ofMTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert- ultra and culture. This could facilitate interventional trials in severe HIV-associated TB.","author":[{"propositions":[],"lastnames":["Barr"],"firstnames":["David","A."],"suffixes":[]},{"propositions":[],"lastnames":["Schutz"],"firstnames":["Charlotte"],"suffixes":[]},{"propositions":[],"lastnames":["Balfour"],"firstnames":["Avuyonke"],"suffixes":[]},{"propositions":[],"lastnames":["Shey"],"firstnames":["Muki"],"suffixes":[]},{"propositions":[],"lastnames":["Kamariza"],"firstnames":["Mireille"],"suffixes":[]},{"propositions":[],"lastnames":["Bertozzi"],"firstnames":["Carolyn","R"],"suffixes":[]},{"propositions":["de"],"lastnames":["Wet"],"firstnames":["Timothy","J"],"suffixes":[]},{"propositions":[],"lastnames":["Dinkele"],"firstnames":["Ryan"],"suffixes":[]},{"propositions":[],"lastnames":["Ward"],"firstnames":["Amy"],"suffixes":[]},{"propositions":[],"lastnames":["Haigh"],"firstnames":["Kathryn","A"],"suffixes":[]},{"propositions":[],"lastnames":["Kanyik"],"firstnames":["Jean-Paul"],"suffixes":[]},{"propositions":[],"lastnames":["Mizrahi"],"firstnames":["Valerie"],"suffixes":[]},{"propositions":[],"lastnames":["Nicol"],"firstnames":["Mark","P"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Lalloo"],"firstnames":["David","G"],"suffixes":[]},{"propositions":[],"lastnames":["Warner"],"firstnames":["Digby","F"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]},{"propositions":[],"lastnames":["Davies"],"firstnames":["Gerry"],"suffixes":[]}],"doi":"10.1016/J.EBIOM.2022.103949","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barr et al. - 2022 - Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis.pdf:pdf","issn":"2352-3964","journal":"eBioMedicine","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"apr","pages":"103949","pmid":"35325781","publisher":"Elsevier","title":"Serial measurement of <i>M. tuberculosis</i> in blood from critically-ill patients with HIV-associated tuberculosis","url":"https://linkinghub.elsevier.com/retrieve/pii/S2352396422001335","volume":"78","year":"2022","bibtex":"@article{Barr2022,\r\nabstract = {Background Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. Methods We established a microscopy method for direct visualisation ofM. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert{\\`{O}} MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients pre- dicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. Findings M. tuberculosis was detected in 27 of28 recruited participants; 25 (89{\\%}) by blood Xpert-ultra, 22 (79{\\%}) by DMN-Tre microscopy, and 21 (75{\\%}) by Myco/F lytic blood culture. Eight (29{\\%}) participants died by 12-week follow- up. In a combined pharmacodynamic model, predicted probabilities ofnegative DMN-Tre microscopy, blood Xpert- ultra, or blood culture after 72 h treatment were 0¢64, 0¢27, and 0¢94, respectively, in those who survived, compared with 0¢23, 0¢06, and 0¢71 in those who died (posterior probability ofslower clearance ofMTBBSI in those that died {\\textgreater}0¢99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolo- nies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0¢13 log- µm/day; 95{\\%}CrI 0¢10?0¢16). Interpretation Pharmacodynamics ofMTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert- ultra and culture. This could facilitate interventional trials in severe HIV-associated TB.},\r\nauthor = {Barr, David A. and Schutz, Charlotte and Balfour, Avuyonke and Shey, Muki and Kamariza, Mireille and Bertozzi, Carolyn R and de Wet, Timothy J and Dinkele, Ryan and Ward, Amy and Haigh, Kathryn A and Kanyik, Jean-Paul and Mizrahi, Valerie and Nicol, Mark P and Wilkinson, Robert J and Lalloo, David G and Warner, Digby F and Meintjes, Graeme A and Davies, Gerry},\r\ndoi = {10.1016/J.EBIOM.2022.103949},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Barr et al. - 2022 - Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis.pdf:pdf},\r\nissn = {2352-3964},\r\njournal = {eBioMedicine},\r\nkeywords = {OA,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {apr},\r\npages = {103949},\r\npmid = {35325781},\r\npublisher = {Elsevier},\r\ntitle = {{Serial measurement of \\textit{M. tuberculosis} in blood from critically-ill patients with HIV-associated tuberculosis}},\r\nurl = {https://linkinghub.elsevier.com/retrieve/pii/S2352396422001335},\r\nvolume = {78},\r\nyear = {2022}\r\n}\r\n","author_short":["Barr, D. 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