In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis

Praharshinie Rupasinghe; Nabila Ismail; Wim Mulders; Robin M. Warren; Lavania Joseph; Dumisani Ngcamu; Thabisile Gwala; Shaheed V. Omar; Jens Vereecken; Bouke C. de Jong; Leen Rigouts; Emanuele Borroni; Daniela M. Cirillo; Thomas Schön; Paolo Miotto; Claudio U. Köser

doi:10.1128/aac.01113-25

In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis

Praharshinie Rupasinghe
, Nabila Ismail
, Wim Mulders
, Robin M. Warren
, Lavania Joseph
, Dumisani Ngcamu
, Thabisile Gwala
, Shaheed V. Omar
, Jens Vereecken
, Bouke C. de Jong
, Leen Rigouts
, Emanuele Borroni
, Daniela M. Cirillo
, Thomas Schön
, Paolo Miotto
, Claudio U. Köser^*

^*Corresponding author for this work

Institute of Tropical Medicine Antwerp
Stellenbosch University
National Health Laboratory Services
IRCCS San Raffaele Scientific Institute
Linköping University
University of Cambridge

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

In vitro experiments with Mycobacterium tuberculosis showed that clofazimine exposure selected for delamanid and pretomanid resistance and mutations in fbiA, fbiC, or fbiD—after the acquisition of Rv0678 mutations where this could be determined. Whether this is also possible in vivo and in an Rv0678 wild-type background has to be studied further. Based on the available evidence, however, we propose that nitroimidazole resistance should not be considered an exclusion criterion for the use of clofazimine.

Original language	English
Journal	Antimicrobial agents and chemotherapy
Volume	69
Issue number	11
DOIs	https://doi.org/10.1128/aac.01113-25
Publication status	Published - 1 Nov 2025
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Mycobacterium tuberculosis
antimicrobial resistance
clofazimine
delamanid
pretomanid

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In-vitro-exposure-to-clofazimine-can-select-for-delamanid-and-pretomanid-resistance-in-mycobacterium-tuberculosis.pdfFinal published version, 213 KBLicence: CC BY

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Rupasinghe, P., Ismail, N., Mulders, W., Warren, R. M., Joseph, L., Ngcamu, D., Gwala, T., Omar, S. V., Vereecken, J., de Jong, B. C., Rigouts, L., Borroni, E., Cirillo, D. M., Schön, T., Miotto, P., & Köser, C. U. (2025). In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 69(11). https://doi.org/10.1128/aac.01113-25

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title = "In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis",

abstract = "In vitro experiments with Mycobacterium tuberculosis showed that clofazimine exposure selected for delamanid and pretomanid resistance and mutations in fbiA, fbiC, or fbiD—after the acquisition of Rv0678 mutations where this could be determined. Whether this is also possible in vivo and in an Rv0678 wild-type background has to be studied further. Based on the available evidence, however, we propose that nitroimidazole resistance should not be considered an exclusion criterion for the use of clofazimine.",

keywords = "Mycobacterium tuberculosis, antimicrobial resistance, clofazimine, delamanid, pretomanid",

author = "Praharshinie Rupasinghe and Nabila Ismail and Wim Mulders and Warren, \{Robin M.\} and Lavania Joseph and Dumisani Ngcamu and Thabisile Gwala and Omar, \{Shaheed V.\} and Jens Vereecken and \{de Jong\}, \{Bouke C.\} and Leen Rigouts and Emanuele Borroni and Cirillo, \{Daniela M.\} and Thomas Sch{\"o}n and Paolo Miotto and K{\"o}ser, \{Claudio U.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 Rupasinghe et al.",

year = "2025",

month = nov,

day = "1",

doi = "10.1128/aac.01113-25",

language = "English",

volume = "69",

journal = "Antimicrobial agents and chemotherapy",

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Rupasinghe, P, Ismail, N, Mulders, W, Warren, RM, Joseph, L, Ngcamu, D, Gwala, T, Omar, SV, Vereecken, J, de Jong, BC, Rigouts, L, Borroni, E, Cirillo, DM, Schön, T, Miotto, P & Köser, CU 2025, 'In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis', Antimicrobial agents and chemotherapy, vol. 69, no. 11. https://doi.org/10.1128/aac.01113-25

TY - JOUR

T1 - In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis

AU - Rupasinghe, Praharshinie

AU - Ismail, Nabila

AU - Mulders, Wim

AU - Warren, Robin M.

AU - Joseph, Lavania

AU - Ngcamu, Dumisani

AU - Gwala, Thabisile

AU - Omar, Shaheed V.

AU - Vereecken, Jens

AU - de Jong, Bouke C.

AU - Rigouts, Leen

AU - Borroni, Emanuele

AU - Cirillo, Daniela M.

AU - Schön, Thomas

AU - Miotto, Paolo

AU - Köser, Claudio U.

PY - 2025/11/1

Y1 - 2025/11/1

N2 - In vitro experiments with Mycobacterium tuberculosis showed that clofazimine exposure selected for delamanid and pretomanid resistance and mutations in fbiA, fbiC, or fbiD—after the acquisition of Rv0678 mutations where this could be determined. Whether this is also possible in vivo and in an Rv0678 wild-type background has to be studied further. Based on the available evidence, however, we propose that nitroimidazole resistance should not be considered an exclusion criterion for the use of clofazimine.

AB - In vitro experiments with Mycobacterium tuberculosis showed that clofazimine exposure selected for delamanid and pretomanid resistance and mutations in fbiA, fbiC, or fbiD—after the acquisition of Rv0678 mutations where this could be determined. Whether this is also possible in vivo and in an Rv0678 wild-type background has to be studied further. Based on the available evidence, however, we propose that nitroimidazole resistance should not be considered an exclusion criterion for the use of clofazimine.

KW - Mycobacterium tuberculosis

KW - antimicrobial resistance

KW - clofazimine

KW - delamanid

KW - pretomanid

UR - https://www.scopus.com/pages/publications/105020922838

U2 - 10.1128/aac.01113-25

DO - 10.1128/aac.01113-25

M3 - Article

C2 - 40980917

SN - 0066-4804

VL - 69

JO - Antimicrobial agents and chemotherapy

JF - Antimicrobial agents and chemotherapy

IS - 11

ER -

In vitro exposure to clofazimine can select for delamanid and pretomanid resistance in Mycobacterium tuberculosis

Abstract

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Keywords

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