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The X(DR)-Files – I want to believe

C U Köser(1)

1:University of Cambridge

Following the endorsement of BPaL(M) by WHO, the need to scale up the capacity for antimicrobial susceptibility testing (AST) for bedaquiline, delamanid and linezolid has become pressing. However, AST for bedaquiline and delamanid, as well as the related compounds clofazimine and delamanid, are challenging due one or more of the following factors: a large spectrum of resistance mutations; a low prevalence of resistance; differences in the intrinsic susceptibility; disagreements about the meaning of ‘resistance’; epistasis; heteroresistance; insufficiently validated phenotypic AST methods; and modest increases in the minimum inhibitory concentrations conferred by some resistance mechanisms. These issues can result in systematic, random or cut-off errors that are exacerbated by the lack of guidance for mitigating them, which risks undermining the trust of clinicians in AST and increases the likelihood of baseline and acquired resistance going undetected.

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