Cryptic resistance mutations associated to misdiagnoses of Multidrug-resistant tuberculosis

Abstract

Understanding Multidrug-resistant tuberculosis cases not detected by rapid phenotypic and genotypic routine clinical tests is essential to improve diagnostics and advance towards personalized TB treatments. Here, we combine WGS with single-colony phenotyping testing to diagnose a MDR strain infecting a patient over nine years. Our investigation revealed the failure of rapid testing assays and genome-based prediction tools to identify the MDR strain. The false negative outcome was caused by uncommon RIF and INH resistance mutations. Despite WGS data helped to personalize treatment, the patient developed XDR-TB, highlighting the importance of coupling new diagnostic methods with appropriate treatment regimens.