Table 2.

Sequencing of MTBDRplus Targets (rpoB, katG, inhA Promoter Region) Done to Resolve Discrepant Results Either Between MTBDRplus and Xpert (Rifampicin) or MTBDRplus and Phenotype (Isoniazid)

				Sequencing
	Locus	MTBDRplus	Comparator Result	Mutation	No. of Isolates	No. With Heteroresistance	Susceptibility Result	Resolved in Favor of Line Probe Assay or Comparator
Rifampicin	rpoB a (n = 29)	S	R	S531L	8	1	R	Xpert
		…	…	H526Y	2	0	R	Xpert
		…	…	D516V	3	1	R	Xpert
		…	…	Q513P	1	0	R	Xpert
		…	…	L511Pb	8 (1 Double mutant with D485N)	1	R	Xpert
		…	…	WT	4	0	S	MTBDRplus
	…	…	…	NR	3	…	…	…
	Discrepant resolution by sequencing			85% (22/26) resistant (resolved in favor of Xpert) 15% (4/26) susceptible (resolved in favor of MTBDRplus)
Isoniazid	katG c (n = 24)	S	R	G312C	1	…	R	pDST
	…	…	…	S315T	3	…	R	pDST
	…	…	…	WT	19	…	S	MTBDRplus
	…			NR 1
	inhA promoterc (n = 24)	S	R	−8 T/C WT	1 23	…	R, S	pDST MTBDRplus
…	Discrepant resolution by sequencing			21% (5/24) resistant (resolved in favor of pDST) 79% (19/24) susceptible (resolved in favor of MTBDRplus)

Sequencing suggested Xpert is more sensitive for rifampicin resistance than MTBDRplus. MTBDRplus detected mutations known to cause isoniazid resistance better than pDST. See Supplementary Methods for how line probe assay results were categorized as discrepant.

Abbreviations: NR, not reportable (did not amplify for sequencing); pDST, phenotypic drug susceptibility testing; R, resistant; S, susceptible; WT, wild type; Xpert, Xpert MTB/RIF.

Only Xpert rifampicin-resistant and MTBDRplus rifampicin-susceptible discrepant sputa were sequenced from the isolate.

L511P is considered borderline by the World Health Organization, which recommends that people found with this mutation be classified as resistant [23].

Discrepant isolates sequenced included only MTBDRplus-susceptible that were phenotypic-resistant (due to contemporaneous programmatic algorithm).