Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs.
OBJECTIVE
Mutations in rrs [nucleotide (nt) 1401], gyrA gene (codons 90, 91 or 94), tlyA, ethA and thyA genes of Mycobacterium tuberculosis (MTB) were evaluated for their usefulness in predicting treatment outcome of kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), ethionamide (ETH) and para-aminosalicylic acid (PAS).


RESULTS
DNA sequence analyses of these genes were performed against 188 MTB isolates obtained from patients put on second-line anti-TB drugs (SLDs) with well-documented clinical history and treatment outcome. Mutations in rrs and gyrA have 100% positive predictive value (PPV) in predicting treatment failure for KM and OFX, while 88·9 and 80% were obtained, respectively, when tlyA and rrs mutations were considered in CPM. For ETH and PAS, the PPV of using ethA and thyA mutations to predict treatment failure was 82·5 and 89·3%, respectively.


CONCLUSIONS
Our study demonstrated high specificities of gene mutations in predicting poor treatment outcome; however, further technical advancement is required to make the molecular detection of resistances to other SLDs feasible in clinical laboratories.


CONCLUSIONS
This is the first study to correlate different polymorphisms of major SLD resistance gene markers with predicted treatment outcome, using an international set of well-documented clinical MTB strains.
Leung
K L
KL
Tuberculosis Reference Laboratory, Public Health Laboratory Service Branch, Centre for Health Protection, Department of Health, Hong Kong Special Administrative Region, Kowloon, Hong Kong.
Yip
C W
CW
Yeung
Y L
YL
Wong
K L
KL
Chan
W Y
WY
Chan
M Y
MY
Kam
K M
KM
D000995:Antitubercular Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D005819:Genetic Markers; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
D000995:Antitubercular Agents; D004269:DNA, Bacterial; D005819:Genetic Markers