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

## TL;DR

Exposure to clofazimine in lab experiments can lead to resistance to other drugs in tuberculosis bacteria.

## Contribution

The study shows that clofazimine can select for resistance to delamanid and pretomanid in M. tuberculosis.

## Key findings

- Clofazimine exposure led to resistance to delamanid and pretomanid in M. tuberculosis.
- Resistance was associated with mutations in fbiA, fbiC, or fbiD genes.
- Rv0678 mutations were observed in some cases.

## 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.