CLINICAL APPLICATION OF RAPID DETERMINANTS OF RESISTANCE IN PULMONARY TB

Abstract

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: In 2009, the Florida Bureau of Public Health Laboratories adopted universal MTBDRplus assay (Hain Lifescience, Nehren, Germany) testing of all diagnosed cases of infection with Mycobacteria tuberculosis (MTB). This study analyzed the concordance of genotypic molecular testing by the MTBDRplus assay with conventional culture susceptibilities by mean inhibitory concentrations (MIC) on all culture-positive pulmonary MTB cases in Florida. METHODS: This was a retrospective, programmatic evaluation that used existing Florida Department of Health data on pulmonary specimens from 2014. Patient identifiers were removed. Of 452 cases of pulmonary tuberculosis, 270 were lacking data on either the MTBDRplus assay, or culture susceptibilities, and were excluded. 182 pulmonary specimens were used. Genotypic resistance to Rifampin (RIF), and Isoniazid (INH), was determined by detection of mutations in the rpoB, and katG or inhA genes, which are associated with resistance to RIF, and INH, respectively. RESULTS: There was concordance between rpoB gene mutation and RIF resistance in 3 of 3 cases. There was concordance between katG gene mutation and INH resistance (MIC >1 ug/mL) in 5 of 5 cases. Of patients who were found to have intermediate INH susceptibility (MIC >0.12 to <1 ug/mL), the mutation in inhA gene was found in 5 of 8 cases. There was no detectable mutation in 3 of 8 cases of intermediate susceptibility. We observe the positive predictive value of the MTBDRplus assay to be 100% and the negative predictive value to be 98%, overall. The median time from specimen collection to reporting for the MTBDRplus assay was 8 days. The median time from specimen collection to reporting for the conventional culture susceptibilities was 44 days. CONCLUSIONS: The MTBDRplus assay proved to be a reliable and timely method for accurate detection of Rifampin and Isoniazid resistance in routine clinical practice, but was not sensitive to reliably detect intermediate susceptibility to INH. One explanation for this is that the assay only probes for a portion of the inhA genes and there are mechanisms of low level resistance outside of the inhA genes. Further development of rapid molecular probes for intermediate susceptibility to INH are needed as this finding impacts the choice of treatment regimens. CLINICAL IMPLICATIONS: The MTBDRplus assay allows for efficient identification of definite cases of drug-resistant pulmonary tuberculosis. We advocate for its clinical use based on the ability to start effective, antitubercular treatment before the results of conventional culture susceptibilities are available. DISCLOSURES: No relevant relationships by Brian Cody Adkinson, source=Web Response No relevant relationships by David Ashkin, source=Web Response No relevant relationships by Alex Ashkin, source=Web Response No relevant relationships by Sara Hulbert, source=Web Response No relevant relationships by Susanna Leonard, source=Web Response No relevant relationships by Marie-Claire Rowlinson, source=Web Response