Whole genome sequencing Mycobacterium tuberculosis directly from sputum identifies more genetic diversity than sequencing from culture

Table 1 Phenotypic and genotypic drug susceptibility testing (DST) results and sensitivity and specificity of genotypic DST relative to phenotypic DST

Drug	Resistance by phenotypic DST	Resistance by genotypic DST	Genotypic DST sensitivity	Genotypic DST specificity
First line drugs
Rifampicin	21/32 (65.6%)	21/33 (63.6%)	21/21 (100%)^a	21/21 (100%)
Isoniazid	22/32 (68.8%)	24/36 (66.7%)	21/22 (95.5%)	23/24 (95.8%)
Ethambutol	7/31 (22.6%)	15/34 (44.1%)	7/7 (100%)	7/15 (46.7%)
Second line drugs
Ofloxacin	0/22 (0.0%)	1/22 (4.5%)	N/A	0/1 (0%)^b
Kanamycin	1/22 (4.5%)	1/22 (4.5%)	1/1 (100%)	1/1 (100%)

Phenotypic DST available for first line drugs for 32 of the 33 patients, and for second line drugs for 22 patients who demonstrated rifampicin drug resistance
^aIn one directly-sequenced sputum samples rifampicin RAVs were missed due to low coverage, although they were identified in the corresponding MGIT sample
^bThis sample had < 1% of colonies grow in the presence of ofloxacin, so is categorised as susceptible but may have low-level or heteroresistance to fluoroquinolones (see main text)

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