Abstract
Multi-drug resistant tuberculosis (TB) threatens TB control worldwide. The MODS assay is a low-cost, high-performance TB diagnostic for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The objective of this study was to explore the potential for extending the MODS assay to rapid 2nd-line DST, and identify candidate drug critical concentrations for prospective testing.
Sputum samples from 94 TB-culture positive patients receiving 2nd-line TB agents were cultured following standardized MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan Meier survival curve analysis.
Candidate critical concentrations were determined for capreomycin (10 ;μg·mL−1), ciprofloxacin (1.25 ;μg·mL−1), cycloserine (40 ;μg·mL−1), ethambutol (10 ;μg·mL−1), ethionamide (5 ;μg·mL−1), kanamycin (5 ;μg·mL−1), para-aminosalicylic acid (10 ;μg·mL−1), and streptomycin (10 ;μg·mL−1). No cut point was identified for the other second line drugs, nor pyrazinamide.
At particular concentrations of some 2nd-line TB drugs this novel Kaplan-Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, 2nd-line TB DST with MODS, offering potential of low-cost 2nd line TB DST capacity.
- Diagnostics
- extensively drug resistant TB
- multi-drug resistance
- second-line drug susceptibility testing
- tuberculosis
- ERS