Table 2. Genotypic and phenotypic drug susceptibility profiles of drug-resistant TB cases, Lebanon*.
| Category |
Drug resistance classification |
||||||||
| MDR |
|
XDR |
|||||||
| Patient ID |
14 |
48 |
125† |
74 |
168 |
185 |
|||
| TB drug | |||||||||
| RIF | Gene | rpoB | S450L | S450L | S450L | S450L | S450L | S450L | |
| Phenotypic | |||||||||
| INH | Genes | katG | S315T | F129S‡ | S315T | S315T | S315T | ||
| inhA | C-15T | ||||||||
| Phenotypic | |||||||||
| PZA | Gene | pncA | Y103Stop | InserA192 | A46P | H71Q | |||
| Phenotypic | ND | ND | ND | ND | ND | ND | |||
| EMB | Gene | embB | Q497R | M306V | M306V | Q497R | Q497R | M306V | |
| Phenotypic | |||||||||
| SM | Genes | rpsL | K43R | K88R | K43R | K43R | |||
| rrs | A908C | ||||||||
| Phenotypic | |||||||||
| AMI/KAN | Gene | rrs | A1401G | A1401G | |||||
| Phenotypic | |||||||||
| FQ | Gene | gyrA | S91P§ | D94A | S91P | D94Y | |||
| Phenotypic | |||||||||
| CAP | Genes | tlyA | InserC313 | ||||||
| rrs | A1401G | A1401G | |||||||
| Phenotypic | ND | ND | ND | ND | ND | ND | |||
| ETH |
Genes | ethA | Deleted¶ | 141 nt del# | Deleted¶ | DelG632 | DelG1338 | ||
| inhA | C-15T | ||||||||
| Phenotypic |
ND |
ND |
ND |
|
ND |
ND |
ND |
||
| MIRU-VNTR type** | 100-32 | 19431-157 | 21404-32 | 10156-32 | 21416-15 | ?-15 | |||
| M. tuberculosis complex lineage†† | 2 (Beijing) | 4 (Euro-American) | 3 (Delhi-CAS) | 2 (Beijing) | 4 (H37Rv-like) | 4 (Haarlem) | |||
*Only genes with detected resistance-associated mutations are shown. No mutation was detected in targets associated with linezolid or bedaquiline and clofazimine resistance. Mutations are shown as amino acid changes with the corresponding codon position, nucleotide changes in promoter regions, or inserted or deleted base (inser or del with position in coding sequence) resulting in a frameshift. Bold text shows mutations concordantly detected by whole-genome sequencing and Deeplex-MycTB (GenoScreen, https://www.genoscreen.fr) in samples subjected to both assays. Other mutations are those detected in samples analyzed by Deeplex-MycTB only. Drug resistance predictions are based on reference data from available scientific literature (8–10), and for pncA also on data from Yadon et al. (14). Black represents phenotypic resistance to the different drugs and gray represents phenotypic susceptibility. For phenotypic testing, levofloxacin was the only fluoroquinolone tested. AMI, amikacin; CAP, capreomycin; EMB, ethambutol; ETH, ethionamide; FQ, fluoroquinolones; KAN, kanamycin; INH, isoniazid; ND, not done; PZA, pyrazinamide; RIF, rifampin; SM, streptomycin. †Deeplex-MycTB result obtained on a primary specimen (sputum). The other results were obtained on indirect samples (primary cultures). ‡Mutation described in association with isoniazid resistance once before by Wang et al. (11). This mutation is not detectable by Anyplex testing. §Detected as a minority variant, at 5.2% in this sample (see text). Percentages of fixation of other mutations within individual samples range from 80.6% to 100%. ¶Putative deletion, as inferred by absence of reads mapped specifically on the corresponding gene target, in contrast to all other, well covered targets. #Internal deletion, resulting in a frameshift, from gene position 859 to 999. **According to MIRU-VNTRPlus website (http://www.miru-vntrplus.org) nomenclature (15). For patient 185, a question mark in the genotype reflects the absence of a detectable allele in locus 4052. ††According to Deeplex-MycTB (spoligotyping and phylogenetic SNPs) and MIRU-VNTRPlus identification, confirmed by whole-genome sequencing results, when done.