TY - JOUR
T1 - Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay
AU - Fitzwater, Sean Patrick
AU - Sechler, G. Andrew
AU - Jave, Oswaldo
AU - Coronel, Jorge
AU - Mendoza, Alberto
AU - Gilman, Robert H.
AU - Friedland, Jon S.
AU - Moore, David A.J.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool 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 second-line DST and to identify critical concentrations of candidate drugs for prospective testing. Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised 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-off point was identified for the other second-line drugs or for pyrazinamide. At particular concentrations of some second-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, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity. Copyright
AB - Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool 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 second-line DST and to identify critical concentrations of candidate drugs for prospective testing. Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised 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-off point was identified for the other second-line drugs or for pyrazinamide. At particular concentrations of some second-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, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity. Copyright
KW - Diagnostics
KW - Extensively drug-resistant tuberculosis
KW - Multidrug resistance
KW - Second-line drug susceptibility testing
KW - Tuberculosis
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U2 - 10.1183/09031936.00059812
DO - 10.1183/09031936.00059812
M3 - Article
C2 - 22903960
AN - SCOPUS:84874931336
SN - 0903-1936
VL - 41
SP - 1163
EP - 1171
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 5
ER -