Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Barr:2022:10.1016/j.ebiom.2022.103949,
author = {Barr, DA and Schutz, C and Balfour, A and Shey, M and Kamariza, M and Bertozzi, CR and de, Wet TJ and Dinkele, R and Ward, A and Haigh, KA and Kanyik, J-P and Mizrahi, V and Nicol, MP and Wilkinson, RJ and Lalloo, DG and Warner, DF and Meintjes, G and Davies, G},
doi = {10.1016/j.ebiom.2022.103949},
journal = {EBioMedicine},
title = {Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis},
url = {http://dx.doi.org/10.1016/j.ebiom.2022.103949},
volume = {78},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 of M. 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® 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 predicted 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 of 28 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 of negative 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 of slower clearance of MTBBSI in those that died >0·99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolonies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean
AU  - Barr,DA
AU  - Schutz,C
AU  - Balfour,A
AU  - Shey,M
AU  - Kamariza,M
AU  - Bertozzi,CR
AU  - de,Wet TJ
AU  - Dinkele,R
AU  - Ward,A
AU  - Haigh,KA
AU  - Kanyik,J-P
AU  - Mizrahi,V
AU  - Nicol,MP
AU  - Wilkinson,RJ
AU  - Lalloo,DG
AU  - Warner,DF
AU  - Meintjes,G
AU  - Davies,G
DO  - 10.1016/j.ebiom.2022.103949
PY  - 2022///
SN  - 2352-3964
TI  - Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2022.103949
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35325781
UR  - http://hdl.handle.net/10044/1/96607
VL  - 78
ER  -
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