TABLE 2.
MICs of 10 antimicrobials tested in combination with rifabutin using the checkerboard broth microdilution method against Mycobacterium abscessus subsp. abscessus and Mycobacterium abscessus subsp. massiliense isolates
| Subspecies and drug | MIC (mg/liter) |
Categorical MIC breakpoints (mg/liter)a |
No. (%) of isolates for which the combination showed synergy (FICI ≤ 0.5) | ||||
|---|---|---|---|---|---|---|---|
| 50% | 90% | Range | Susceptible | Intermediate | Resistant | ||
| M. abscessus subsp. abscessus (n = 13)b | |||||||
| Rifabutin | 4* | 8* | 1 to 32 | ≤2 (4, 30.8) | >2 (9, 69.2) | ||
| Clarithromycin | 0.5* | 1* | 0.25 to 1 | ≤2 (13, 100.0) | 4 (0, 0) | ≥8 (0, 0) | 8 (61.5) |
| Amikacin | 8* | 16 | 1 to 32* | ≤16 (12, 92.3) | 32 (1, 7.7) | ≥64 (0, 0) | 7 (53.8) |
| Cefoxitin | 32 | 32 | 2 to 32 | ≤16 (6, 46.2) | 32-64 (7, 53.8) | ≥128 (0, 0) | 4 (30.8) |
| Ceftibuten | 64* | 128 | 8 to 128 | ≤16 (1, 7.7) | 32-64 (8, 61.5) | ≥128 (4, 30.8) | 8 (61.5) |
| Clofazimine | 1 | 2 | 0.5 to 2 | ≤2 (13, 100.0) | ≥8 (0, 0) | 0 (0) | |
| Doxycycline | >64 | >64 | 32 to >64 | ≤1 (0, 0) | 2–4 (0, 0) | ≥8 (13, 100.0) | 0 (0) |
| Imipenem | 1* | 2* | 0.5 to 8 | ≤4 (12, 92.3) | 8–16 (1, 7.7) | ≥32 (0, 0) | 13 (100.0) |
| Linezolid | 16 | 32 | 4 to 32 | ≤8 (5, 38.5) | 16 (3, 23.1) | ≥32 (5, 38.5) | 4 (30.8) |
| Moxifloxacin | 32 | 32 | 8 to 256 | ≤1 (0, 0) | 2 (0, 0) | ≥4 (13, 100) | 1 (7.7) |
| Tigecycline | 0.12* | 0.25* | 0.06 to 0.25 | ≤0.5 (13, 100.0) | 1 (0, 0) | ≥2 (0, 0) | 10 (76.9) |
| M. abscessus subsp. massiliense (n = 13)c | |||||||
| Rifabutin | 8 | 16 | 0.12 to 16 | ≤2 (3, 23.1) | >2 (10, 76.9) | ||
| Clarithromycin | 0.12 | 0.25* | <0.03 to >256 | ≤2 (12, 92.3) | 4 (0, 0) | ≥8 (1, 7.7) | 3 (23.1) |
| Amikacin | 16 | 16 | 4 to 32 | ≤16 (11, 84.6) | 32 (2, 15.4) | ≥64 (0, 0) | 2 (15.4) |
| Cefoxitin | 32 | 32 | 4 to 64 | ≤16 (4, 30.8) | 32–64 (9, 69.2) | ≥128 (0, 0) | 2 (15.4) |
| Ceftibuten | 128 | 128 | 32 to 256 | ≤16 (0, 0) | 32–64 (4, 30.8) | ≥128 (9, 69.2) | 2 (15.4) |
| Clofazimine | 2 | 2 | 0.5 to 2 | ≤2 (13, 100.0) | ≥8 (0, 0) | 0 (0) | |
| Doxycycline | >64 | >64 | 4 to >64 | ≤1 (0, 0) | 2-4 (1, 7.7) | ≥8 (12, 92.3) | 0 (0) |
| Imipenem | 2* | 8 | 0.25 to 32 | ≤4 (10, 76.9) | 8–16 (2, 15.4) | ≥32 (1, 7.7) | 9 (69.2) |
| Linezolid | 16 | 16 | 0.5 to 32 | ≤8 (6, 46.2) | 16 (5, 38.5) | ≥32 (2, 15.4) | 2 (15.4) |
| Moxifloxacin | 32 | 32 | 2 to 128 | ≤1 (0, 0) | 2 (1, 7.7) | ≥4 (12, 92.3) | 0 (0) |
| Tigecycline | 0.12* | 0.25* | 0.06 to 0.25 | ≤0.5 (13, 100.0) | 1 (0, 0) | ≥2 (0, 0) | 9 (69.2) |
Data in parentheses represent the number, percent, of isolates with the indicated result. Data in bold indicate the MIC breakpoints applied in this study. The results of the broth microdilution susceptibility testing for two-drug combinations read at the minimal fractional inhibitory concentration index (FICI) are marked by an asterisk (*) if a fourfold or more decrease was observed when the drug was tested in rifabutin-based combinations (as shown here) compared to when it was tested alone (Table 1). For the case of rifabutin, the two-drug combination results refer to those for rifabutin combined with clarithromycin.
There were T28 (n = 10) and C28 (n = 3) sequevars among the 13 isolates. None of the isolates had rrl mutations.
A truncated erm41 (n = 12), the C28 sequevar (n = 1), and rrl mutations (A2057G, A2058G; n = 2) were found among the 13 isolates.