Figures
- FIGURE 1
The multidrug-resistant (MDR) tuberculosis (TB) shorter regimen: schematic representation of a diagnostic algorithm. #: critical concentration not recommended. Km: kanamycin; Mfx: moxifloxacin; Pto: prothionamide; Cfz: clofazimine; Z: pyrazinamide; Hhigh-dose: high-dose isoniazid; E: ethambutol; R: rifampicin; LPA: line probe assay; R-R: rifampicin-resistant; DST: drug susceptibility testing.
Tables
- TABLE 1
Clinical interpretation of the rapid test for tuberculosis “GenoType MTBDRsl V2 (Hain Lifescience)”
Drug Failing WT band Developing mutation band Mutation Classification: final BCVs Final interpretation for clinicians OFX-LFX MFX AM CM KM OFX
LFX
MFXgyrA WT1 -
-G88A
G88CHigh
HighIndet
High#No OFX-LFX use, not informative for MFX
No OFX-LFX use, not informative for MFXgyrA WT2 gyrA MUT1
gyrA MUT2A90V
S91PHigh
HighHigh
HighNo OFX-LFX use, higher dosage of MFX?
No OFX-LFX use, higher dosage of MFX?gyrA WT3 gyrA MUT3A
gyrA MUT3B
-
gyrA MUT3C
gyrA MUT3DD94A
D94N
D94Y
D94G
D94HHigh
High
High
High
HighHigh
High
High
High
IndetNo OFX-LFX use, higher dosage of MFX?
No use of fluoroquinolones
No OFX-LFX use, higher dosage of MFX?
No use of fluoroquinolones
No OFX-LFX use, not informative for MFXgyrB WT gyrB MUT1
gyrB MUT2N538D¶
E540V+Indet
IndetIndet
IndetNot informative
Not informativeAM
CM
KMrrs WT1 rrs MUT1
-a1401g
c1402tHigh
IndetHigh
HighHigh
High#No use of second-line injectables
No CM use, not informative for AM- KMrrs WT2 rrs MUT2 g1484t High High High# No AM-CM use, not informative for KM KM eis WT1 - g-37t Minimal# Not informative eis WT2 eis MUT1
-
-c-14t
c-12t
g-10aHigh
Minimal#
HighNo use of kanamycin
Not informative
No use of kanamycineis WT3 - c-2a Indet Not informative Modified from [13]. OFX: ofloxacin; LFX: levofloxacin; MFX: moxifloxacin, AM: amikacin; CM: capreomycin; KM: kanamycin; BCVs: best confidence values; Indet: indeterminate. #: the association of these mutation is based on nominal p-values only (putative, not corrected; refer to Miotto et al. [13]); ¶: N499D; +: E501V.
- TABLE 2
Diagnostic accuracy and sensitivity values for anti-tuberculosis drugs (graded mutations identified by Miotto et al. [13] were used within the new classification of the World Health Organization [12]).
Drug class Drug (genomic region targeted) Clinical interpretation of graded mutations as marker of resistance (high+moderate+minimal) Diagnostic accuracy % Sensitivity % First-line Rifampicin (rpoB) 94 90.5 Isoniazid (katG, inhA-mabA, furA, mshA) 80.7 78.3 Second-line (group A) Ofloxacin/levofloxacin (gyrA, gyrB)
Moxifloxacin (gyrA, gyrB)90.9
9481.7
89.2Second-line (group B) Amikacin (rrs) 91.8 78.8 Capreomycin (rrs, tlyA) 92 71.3 Kanamycin (rrs, eis, whiB7) 87.7 68.3 Streptomycin (rpsL, rrs, gidB, tap, whiB7) 76.4 61.3 Second-line (group C) Ethionamide/prothionamide (inhA-mabA, ethA, mshA) 67.5 48.5 Second-line (group D) Pyrazinamide (pncA) 76.8 53.1
