D-1127. Ethambutol and Streptomycin Testing of Mycobacterium tuberculosis Using the Microscopic-Observation Drug-Susceptibility (MODS) Assay
Session: Poster Session: Laboratory Testing for Mycobacteria
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: The MODS assay is a rapid method for M. tuberculosis diagnosis and drug-susceptibility testing. The validity of MODS for ethambutol and streptomycin drug-susceptibility testing has been poor relative to other first-line drugs. This study aimed to improve its validity by defining the optimal critical concentration needed for these drugs. Methods: Decontaminated sputum samples (n=48) were tested using the MODS method with concurrent serial 1:2 dilutions of ethambutol and streptomycin solutions in standard 7H9 broth. Ethambutol concentrations ranged from 20 to 0.3625 µg/mL and streptomycin from 8.0 to 0.125 µg/mL. Cultures were incubated at 37ºC. M. tuberculosis growth was observed by light microscopy. Reference standard drug-susceptibility testing was done using the Tetrazolium Microplate Assay. Results: Optimal critical concentrations for defining drug resistance in MODS were 5.0 μg/mL for ethambutol (Youden’s Index: 0.68, Test efficiency: 86%) and 1.0 μg/mL for streptomycin (Youden’s Index: 0.37, Test efficiency: 74%). Area under the ROC curve was 0.68 (95% CI: 0.21 to 0.96) for streptomycin and 0.87 (95% CI: 0.23 to 1.0) for ethambutol. MODS MIC50 was 1.68 μg/mL for ethambutol and 2.16 μg/mL for streptomycin. MODS MIC90 was 8.25 μg/mL for ethambutol and 8.85 μg/mL for streptomycin. Conclusions: The accuracy of ethambutol and streptomycin drug-susceptibility testing in the MODS assay was improved by modifying drug critical concentrations.
Carlton Evans1, Erik Ramos2, Jessica Alvarado2, Beatriz Herrera2, Maria Hollm-Delgado3, Robert Gilman, MD, DTMH4, Rosario Montoya5, Willy Quino2 and  M. G. Hollm-Delgado, None., (1)Imperial College London, (2)Universidad Peruana Cayetano Heredia, (3)Universite de Montréal, Surco, Peru, (4)Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, (5)AB PRISMA