Performance of MTBDR plus for detecting high/low levels of Mycobacterium tuberculosis resistance to isoniazid.
METHODS
We recently evaluated the Genotype MTBDR test for assessing Mycobacterium tuberculosis resistance to rifampicin (RMP) and isoniazid (INH) by detecting mutations in rpoB (codons 511-533) and katG (codon 315). A new version of the test, MTBDR plus, has been designed to also detect mutations in the regulatory region of inhA.


OBJECTIVE
To evaluate the performance of MTBDR plus over MTBDR.


RESULTS
In 113 isolates, MTBDR plus detected all 76 RMP-resistant (RMP-R) strains and all 64 INH-resistant (INH-R) strains with KatG-315 mutations, 59 of which displayed a high level of INH resistance. It also identified 18 strains undetectable by MTBDR, without mutation in KatG-315 but with a -15 C-->T mutation in the regulatory region of inhA, of which 15 displayed a low level of INH resistance. Thirteen INH-R strains, which mainly harboured mutations in KatG at positions other than 315, were undetected by MTBDR plus.


CONCLUSIONS
MTBDR plus retains the accuracy shown by MTBDR in detecting RMP resistance and is more sensitive in detecting INH resistance (86% vs. 67%), particularly at low levels (minimum inhibitory concentration<1 mg/l, 69% vs. 17%). The negative predictive value of the test (the probability of a strain with a wild-type test being susceptible to INH) is >98% when the rate of INH is <10%, as it is in France.
Brossier
F
F
National Reference Centre for Mycobacteria, Hôpital Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie (UPMC), Université Paris 06, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Veziris
N
N
Jarlier
V
V
Sougakoff
W
W
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001681:Biological Assay / Q000379:methods* / Q000706:statistics & numerical data; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin