Table 2. Open in new tab Likely...

	Xpert		MTBDRplus
1	R		A	S culture		S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
2	R		E	S sputum		S	760600 A>C Fixed	L533P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
3	R		B	S culture	R culture	S	761155 C>T Near fixed (>98%)	D516Y	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
4			A	R culture	S sputum	S	761095 T>C Near fixed (>98%)	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
5			A	R culture	S sputum	S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
6			C	R culture	S culture	R	761128 C>T Fixed	S522L	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
7			B	R culture	S culture	R	761110 A>T Near fixed (>98%)	D516A	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
8	R		B	S culture		R	761104 TCATGGA>A Low-frequency variant (2%)	515 6bp del	False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture	Resistant	RIF resistant
9	R		D	R sputum	S culture	R	761139 C>T Heteroresistance (18%)	H526Y	False-negative MTBDRplus due to loss of minor variant in culture	Resistant	RIF resistant
10	R	S	E	R culture		R	761155 C>T Fixed	S531L	Unknown (possible administrative error)	Resistant	RIF resistant
11	R		–	S culture		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
12	R		–	S sputum		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
13	R		–	S culture	S sputum	S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
14	R	R	–	S sputum	S sputum	S	WT		False-positive Xpert	Susceptible	Resistant (?)
15	S		–	R	R	S	WT		False-positive MTBDRplus	Susceptible	Susceptible

Xpert

MTBDRplus

Patient

Xpert probe^a

RIF MIC

rpoB variant (genome position and coverage on WGS)

E. coli numbering

Most likely mechanism

Likely true RIF resistance status

Expected result if Xpert is used to resolve discrepancy

S culture

761095 T>C Fixed

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

S sputum

760600 A>C Fixed

L533P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

S culture

R culture

761155 C>T Near fixed (>98%)

D516Y

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S sputum

761095 T>C Near fixed (>98%)

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S sputum

761095 T>C Fixed

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S culture

761128 C>T Fixed

S522L

False-negative MTBDRplus in absence of mutant probe^b

Resistant

RIF resistant

R culture

S culture

761110 A>T Near fixed (>98%)

D516A

False-negative MTBDRplus in absence of mutant probe^b

Resistant

RIF resistant

S culture

761104 TCATGGA>A Low-frequency variant (2%)

515 6bp del

False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture

Resistant

RIF resistant

R sputum

S culture

761139 C>T Heteroresistance (18%)

H526Y

False-negative MTBDRplus due to loss of minor variant in culture

Resistant

RIF resistant

R culture

761155 C>T Fixed

S531L

Unknown (possible administrative error)

Resistant

RIF resistant

–

S culture

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S sputum

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S culture

S sputum

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S sputum

False-positive Xpert

Susceptible

Resistant (?)

–

False-positive MTBDRplus

Susceptible

	Xpert		MTBDRplus
1	R		A	S culture		S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
2	R		E	S sputum		S	760600 A>C Fixed	L533P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
3	R		B	S culture	R culture	S	761155 C>T Near fixed (>98%)	D516Y	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
4			A	R culture	S sputum	S	761095 T>C Near fixed (>98%)	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
5			A	R culture	S sputum	S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
6			C	R culture	S culture	R	761128 C>T Fixed	S522L	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
7			B	R culture	S culture	R	761110 A>T Near fixed (>98%)	D516A	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
8	R		B	S culture		R	761104 TCATGGA>A Low-frequency variant (2%)	515 6bp del	False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture	Resistant	RIF resistant
9	R		D	R sputum	S culture	R	761139 C>T Heteroresistance (18%)	H526Y	False-negative MTBDRplus due to loss of minor variant in culture	Resistant	RIF resistant
10	R	S	E	R culture		R	761155 C>T Fixed	S531L	Unknown (possible administrative error)	Resistant	RIF resistant
11	R		–	S culture		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
12	R		–	S sputum		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
13	R		–	S culture	S sputum	S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
14	R	R	–	S sputum	S sputum	S	WT		False-positive Xpert	Susceptible	Resistant (?)
15	S		–	R	R	S	WT		False-positive MTBDRplus	Susceptible	Susceptible

Xpert

MTBDRplus

Patient

Xpert probe^a

RIF MIC

rpoB variant (genome position and coverage on WGS)

E. coli numbering

Most likely mechanism

Likely true RIF resistance status

Expected result if Xpert is used to resolve discrepancy

S culture

761095 T>C Fixed

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

S sputum

760600 A>C Fixed

L533P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

S culture

R culture

761155 C>T Near fixed (>98%)

D516Y

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S sputum

761095 T>C Near fixed (>98%)

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S sputum

761095 T>C Fixed

L511P

False-negative MTBDRplus in absence of mutant probe^b

Low-level resistant (disputed mutation)

RIF resistant

R culture

S culture

761128 C>T Fixed

S522L

False-negative MTBDRplus in absence of mutant probe^b

Resistant

RIF resistant

R culture

S culture

761110 A>T Near fixed (>98%)

D516A

False-negative MTBDRplus in absence of mutant probe^b

Resistant

RIF resistant

S culture

761104 TCATGGA>A Low-frequency variant (2%)

515 6bp del

False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture

Resistant

RIF resistant

R sputum

S culture

761139 C>T Heteroresistance (18%)

H526Y

False-negative MTBDRplus due to loss of minor variant in culture

Resistant

RIF resistant

R culture

761155 C>T Fixed

S531L

Unknown (possible administrative error)

Resistant

RIF resistant

–

S culture

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S sputum

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S culture

S sputum

Unknown (possible administrative error or false-positive Xpert)

Susceptible

Susceptible if human error; resistant if false-positive Xpert

–

S sputum

False-positive Xpert

Susceptible

Resistant (?)

–

False-positive MTBDRplus

Susceptible

Table 2.

Open in new tab

Likely mechanisms for discordances between molecular assays in patients with one or more discordances between two molecular tests and results available for the MIC of rifampicin (RIF MIC) on liquid culture and WGS

	Xpert			MTBDRplus
Patient	1	2	Xpert probe^a	1	2	RIF MIC	rpoB variant (genome position and coverage on WGS)	E. coli numbering	Most likely mechanism	Likely true RIF resistance status	Expected result if Xpert is used to resolve discrepancy
1	R		A	S culture		S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
2	R		E	S sputum		S	760600 A>C Fixed	L533P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
3	R		B	S culture	R culture	S	761155 C>T Near fixed (>98%)	D516Y	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
4			A	R culture	S sputum	S	761095 T>C Near fixed (>98%)	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
5			A	R culture	S sputum	S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
6			C	R culture	S culture	R	761128 C>T Fixed	S522L	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
7			B	R culture	S culture	R	761110 A>T Near fixed (>98%)	D516A	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
8	R		B	S culture		R	761104 TCATGGA>A Low-frequency variant (2%)	515 6bp del	False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture	Resistant	RIF resistant
9	R		D	R sputum	S culture	R	761139 C>T Heteroresistance (18%)	H526Y	False-negative MTBDRplus due to loss of minor variant in culture	Resistant	RIF resistant
10	R	S	E	R culture		R	761155 C>T Fixed	S531L	Unknown (possible administrative error)	Resistant	RIF resistant
11	R		–	S culture		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
12	R		–	S sputum		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
13	R		–	S culture	S sputum	S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
14	R	R	–	S sputum	S sputum	S	WT		False-positive Xpert	Susceptible	Resistant (?)
15	S		–	R	R	S	WT		False-positive MTBDRplus	Susceptible	Susceptible

	Xpert			MTBDRplus
Patient	1	2	Xpert probe^a	1	2	RIF MIC	rpoB variant (genome position and coverage on WGS)	E. coli numbering	Most likely mechanism	Likely true RIF resistance status	Expected result if Xpert is used to resolve discrepancy
1	R		A	S culture		S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
2	R		E	S sputum		S	760600 A>C Fixed	L533P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
3	R		B	S culture	R culture	S	761155 C>T Near fixed (>98%)	D516Y	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
4			A	R culture	S sputum	S	761095 T>C Near fixed (>98%)	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
5			A	R culture	S sputum	S	761095 T>C Fixed	L511P	False-negative MTBDRplus in absence of mutant probe^b	Low-level resistant (disputed mutation)	RIF resistant
6			C	R culture	S culture	R	761128 C>T Fixed	S522L	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
7			B	R culture	S culture	R	761110 A>T Near fixed (>98%)	D516A	False-negative MTBDRplus in absence of mutant probe^b	Resistant	RIF resistant
8	R		B	S culture		R	761104 TCATGGA>A Low-frequency variant (2%)	515 6bp del	False-negative MTBDRplus due to absence of mutant probe^b or loss of minor variant in culture	Resistant	RIF resistant
9	R		D	R sputum	S culture	R	761139 C>T Heteroresistance (18%)	H526Y	False-negative MTBDRplus due to loss of minor variant in culture	Resistant	RIF resistant
10	R	S	E	R culture		R	761155 C>T Fixed	S531L	Unknown (possible administrative error)	Resistant	RIF resistant
11	R		–	S culture		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
12	R		–	S sputum		S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
13	R		–	S culture	S sputum	S	WT		Unknown (possible administrative error or false-positive Xpert)	Susceptible	Susceptible if human error; resistant if false-positive Xpert
14	R	R	–	S sputum	S sputum	S	WT		False-positive Xpert	Susceptible	Resistant (?)
15	S		–	R	R	S	WT		False-positive MTBDRplus	Susceptible	Susceptible

R, resistant; S, susceptible; RIF, rifampicin.

Xpert probe responsible for identification inferred from WGS data.

Variant can only be detected by absence of the WT band, which is more error prone compared with detection of a mutant probe.¹⁵ ^, ²³

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