Cryptic Resistance Mutations Associated With Misdiagnoses of Multidrug-Resistant Tuberculosis. (15th April 2019)

• Record Type: Journal Article
• Authors: Cancino-Muñoz, Irving; Moreno-Molina, Miguel; Furió, Victoria; Goig, Galo A; Torres-Puente, Manuela; Chiner-Oms, Álvaro; Villamayor, Luis M; Sanz, Francisco; Guna-Serrano, María Remedio; Comas, Iñaki
• Is Part Of: Journal of infectious diseases. Volume 220:Number 2(2019)
• Page Start: 316
• Page End: 320
• Publication Date: 2019-04-15
• Subjects: Tuberculosis -- drug resistance -- whole-genome sequencing -- individualized treatment -- cryptic mutations; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz104
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Understanding why some multidrug-resistant tuberculosis cases are not detected by rapid phenotypic and genotypic routine clinical tests is essential to improve diagnostic assays and advance toward personalized tuberculosis treatment. Here, we combine whole-genome sequencing with single-colony phenotyping to identify a multidrug-resistant strain that had infected a patient for 9 years. Our investigation revealed the failure of rapid testing and genome-based prediction tools to identify the multidrug-resistant strain. The false-negative findings were caused by uncommon rifampicin and isoniazid resistance mutations. Although whole-genome sequencing data helped to personalize treatment, the patient developed extensively drug-resistant tuberculosis, highlighting the importance of coupling new diagnostic methods with appropriate treatment regimens. Abstract : Whole-genome sequencing identified a case of multidrug-resistant tuberculosis missed by routine culture and molecular susceptibility tests. Rare rifampin and isoniazid resistance mutations were behind the false-negative results. Whole-genome sequencing helped manage the case despite its further progression to extensively drug-resistant tuberculosis.