IMPROVING THE DIAGNOSIS OF MULTI-RESISTANT TUBERCULOSIS: A COMPARATIVE STUDY OF PHENOTYPIC AND GENOTYPIC METHODS
Name: LUIZ GUILHERME SCHMIDT CASTELLANI
Publication date: 18/09/2025
Examining board:
Name |
Role |
|---|---|
| ARTEMIR COELHO DE BRITO | Examinador Externo |
| CARLOS GRAEFF TEIXEIRA | Examinador Interno |
| LUCILAINE FERRAZOLI | Examinador Externo |
| MOISES PALACI | Presidente |
| REYNALDO DIETZE | Examinador Interno |
Summary: Tuberculosis remains globally the leading cause of death among infectious diseases, with drug-resistant forms affecting over 400,000 individuals annually. This study addresses the urgent need for accessible diagnostic technologies, like the Swab Culture Optimized Test (SCOT-TB), a test that can be done in laboratories with low-complexity infrastructure, or even in rural areas. For that, minimum inhibitory concentrations (MIC) of rifampicin, isoniazid, levofloxacin, moxifloxacin, linezolid, pretomanid and bedaquiline were evaluated in the egg-based Ogawa-Kudoh medium. 65 Mycobacterium tuberculosis strains with diverse resistance profiles were tested in 6 different methods: MIC in Ogawa-Kudoh, MIC in Middlebrook 7H9 broth (EUCAST reference method), BD BACTEC™ MGIT™ SIRE, Xpert® MTB/RIF Ultra, GenoType MTBDRplus and GenoType MTBDRsl. The results indicate the epidemiological cut-off values of 20 mg/L for rifampicin, 0.2 mg/L for isoniazid, 4 mg/L for pretomanid and 1 mg/L for levofloxacin, moxifloxacin and linezolid in Ogawa-Kudoh. The agreement with the EUCAST reference method for MIC in Ogawa-Kudoh (=0.983) and BD BACTEC™ MGIT™ SIRE (=0.954) was almost perfect, but for Xpert® MTB/RIF Ultra (=0.536), GenoType MTBDRplus (=0.754) and GenoType MTBDRsl (=0.735) varied from weak to moderate. This research provides important data about discordances between phenotypic and genotypic antimicrobial susceptibility tests, particularly for strains with borderline resistance and disputed mutations. It also presents crucial data for stablishing critical concentrations in Ogawa-Kudoh medium, and supports the development of more accessible and cost-effective diagnostic tools like SCOT-TB to improve Tuberculosis control in poverty-stricken regions with a high Tuberculosis burden.
