Delamanid or pretomanid for treatment of multidrug resistant tuberculosis---spoilt for choice?

MDR TB treatment is now facing the perils of emerging resistance to BDQ(bedaquiline) and DLM(delaminid). Both DLM and PRT(pretomanid) belong to the nitroimidazole group of drugs. Drug resistance in Mycobacterium Tuberculosis (MTB) is an ever changing, continuous and evolving process whereby the bacteria finds new genetic mutations to escape destruction by the newer drugs. DLM and PRT belong to the same class of drugs and resistance to both drugs have been described with mutations in five M. tuberculosis genes (ddn, fgd1, fbiA, fbiB, and fbiC) resulting in very high level of cross-resistance between the two drugs. Mutations in Rv2983 (fbiD), fbiB genes and some ddn allelles (S78Y, Y133C) can cause resistance to PRT but the strains may retain susceptibility to DLM. These reasons may lead to slight preference for DLM as compared to PRT. Such implications may be also kept in mind while treatment of MDR-TB with DLM and PRT.