Imperial College London
Alternate

Professor Francis Drobniewski

Faculty of Medicine, Department of Infectious Disease

Chair in Global Health and Tuberculosis
 
 
 
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Contact

 

f.drobniewski

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gonzalo:2022:10.3390/antibiotics11101274,
author = {Gonzalo, X and Bielecka, MK and Tezera, L and Elkington, P and Drobniewski, F},
doi = {10.3390/antibiotics11101274},
journal = {Antibiotics},
pages = {1--9},
title = {Anti-tuberculosis activity of three carbapenems, clofazimine and nitazoxanide using a novel ex vivo phenotypic drug susceptibility model of human tuberculosis},
url = {http://dx.doi.org/10.3390/antibiotics11101274},
volume = {11},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We evaluated a novel physiological 3-D bioelectrospray model of the tuberculosis (TB) granuloma to test the activity of a known anti-TB drug, clofazimine; three carbapenems with potential activity, including one currently used in therapy; and nitazoxanide, an anti-parasitic compound with possible TB activity (all chosen as conventional drug susceptibility was problematical). PBMCs collected from healthy donors were isolated and infected with M. tuberculosis H37Rv lux (i.e., luciferase). Microspheres were generated with the infected cells; the anti-microbial compounds were added and bacterial luminescence was monitored for at least 21 days. Clavulanate was added to each carbapenem to inhibit beta-lactamases. M. tuberculosis (MTB) killing efficacy was dose dependent. Clofazimine was the most effective drug inhibiting MTB growth at 2 mg/L with good killing activity at both concentrations tested. It was the only drug that killed bacteria at the lowest concentration tested. Carbapenems showed modest initial activity that was lost at around day 10 of incubation and clavulanate did not increase killing activity. Of the carbapenems tested, tebipenem was the most efficient in killing MTB, albeit at a high concentration. Nitazoxanide was effective only at concentrations not achievable with current dosing (although this might partly have been an artefact related to extensive protein binding).
AU  - Gonzalo,X
AU  - Bielecka,MK
AU  - Tezera,L
AU  - Elkington,P
AU  - Drobniewski,F
DO  - 10.3390/antibiotics11101274
EP  - 9
PY  - 2022///
SN  - 2079-6382
SP  - 1
TI  - Anti-tuberculosis activity of three carbapenems, clofazimine and nitazoxanide using a novel ex vivo phenotypic drug susceptibility model of human tuberculosis
T2  - Antibiotics
UR  - http://dx.doi.org/10.3390/antibiotics11101274
UR  - https://www.mdpi.com/2079-6382/11/10/1274
UR  - http://hdl.handle.net/10044/1/100229
VL  - 11
ER  -
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