TABLE 2.
Susceptibility of representative linezolid-resistant M. abscessus ATCC 19977 strains to oxazolidinones and other anti-M. abscessus drugs
| Class and druga | WT (μM) |
LZD_r1 (23S) (μM) |
LZD_r6 (L3) (μM) |
LZD_r8 (TetR) (μM) |
LZD_r8 (+MAB_4384)b (μM) |
CLR_r1 (23S)c (μM) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | MIC50 | MIC90 | MIC50 | MIC90 | MIC50 | MIC90 | MIC50 | MIC90 | MIC50 | MIC90 | |
| Oxazolidinones | ||||||||||||
| LZD | 3.5 | 12 | >100 | >100 | 30 | >100 | 8 | 35 | 5 | 15 | 5 | 15 |
| TZD | 0.4 | 3 | 70 | >100 | 5 | 20 | 1.5 | 6 | 1 | 4.5 | 2 | 8 |
| SZD | 4 | 12 | >100 | >100 | 40 | >100 | 20 | 90 | 5 | 20 | 4.5 | 20 |
| SZD-M1 | 4 | 15 | >100 | >100 | 40 | >100 | 3 | 15 | 4 | 15 | 3 | 15 |
| DZD | 2.5 | 10 | 100 | >100 | 25 | 80 | 2.5 | 12 | 3 | 12 | 5 | 20 |
| TBI-223 | 4 | 15 | >100 | >100 | 60 | >100 | 8 | 60 | 5 | 20 | 5 | 25 |
| Other anti-M. abscessus drugs | ||||||||||||
| CLR | 0.3 | 1.5 | 0.8 | 25 | 0.2 | 3.0 | 0.5 | 2 | 0.2 | 2 | >100 | >100 |
| AZT | 3.5 | 12 | 12 | >100 | 3 | 15 | 3.5 | 15 | 2.5 | 15 | >100 | >100 |
| AMK | 3 | 12 | 50 | >100 | 5 | 20 | 3.5 | 12 | 4 | 12.5 | 4 | 15 |
| TGC | 1 | 3 | 1.2 | 25 | 1 | 4 | 1.2 | 3 | 1 | 3 | 1 | 5 |
| OMC | 2 | 12 | 8 | 50 | 3 | 15 | 4 | 12.5 | 4 | 12 | 3 | 12 |
| FOX | 10 | 20 | 12 | 25 | 10 | 20 | 10 | 20 | 10 | 20 | 12 | 20 |
| BDQ | 0.3 | 0.5 | 0.4 | 1 | 0.3 | 0.6 | 0.15 | 0.4 | 0.2 | 0.4 | 0.3 | 0.6 |
| CFZ | 6 | 25 | 50 | >100 | 8 | 25 | 4 | 25 | 5 | 25 | 13 | 40 |
| RFB | 0.3 | 1 | 0.5 | 1 | 0.5 | 1 | 0.5 | 1 | 0.5 | 1.2 | 0.8 | 1 |
| MXF | 0.5 | 2.5 | 1.5 | 4 | 1 | 3 | 1 | 3 | 1 | 3 | 2 | 4 |
| SPR719 | 0.25 | 1 | 0.2 | 6 | 0.2 | 1 | 1.5 | 15 | 0.3 | 2.5 | 0.8 | 1.5 |
Drug: LZD, linezolid; TZD, tedizolid; SZD, sutezolid; SZD-M1, sutezolid metabolite; DZD, delpazolid; CLR, clarithromycin; AZT, azithromycin; AMK, amikacin; TGC, tigecycline; OMC, omadacycline; FOX, cefoxitin; BDQ, bedaquiline; CFZ, clofazimine; RFB, rifabutin, MXF, moxifloxacin.
Strain LZD_r8 carrying a frameshift mutation in the tetR gene MAB_4384 (Table 1) complemented with a wild-type copy of MAB_4384 expressed under the control of the hsp60 promoter as described previously (pMV306-hsp60-MAB_4384 [16]). Strain LZD_r8 harboring pMV306-hsp60 without inserted tetR gene did not show any MIC shift.
CLR-resistant strain M. abscessus ATCC 19977 harboring mutation A2270G in the 23S rRNA (14).