TABLE 2.
In vitro activity of LYS228 against Enterobacteriaceae isolates
| Isolate type and test agent | MIC (μg/ml) |
% susceptiblea | ||
|---|---|---|---|---|
| Range | MIC50 | MIC90 | ||
| Enterobacteriaceae (n = 271) | ||||
| LYS228 | ≤0.06 to 64 | 0.25 | 1 | NAb |
| Aztreonam | ≤0.06 to >64 | 16 | >64 | 45.0 |
| Ceftazidime | ≤0.06 to >64 | 16 | >64 | 42.8 |
| Ceftazidime-avibactam | ≤0.06/4 to >64/4 | 0.5/4 | >64/4 | 87.1 |
| Cefepime | ≤0.06 to >64 | 2 | >64 | 52.0 |
| Meropenem | ≤0.06 to >64 | 0.12 | 32 | 68.6 |
| Tigecycline | 0.12 to 8 | 1 | 4 | 86.0 |
| CRE isolates (n = 77)c | ||||
| LYS228 | ≤0.06 to 64 | 0.5 | 4 | NA |
| Aztreonam | ≤0.06 to >64 | >64 | >64 | 5.2 |
| Ceftazidime | 1 to >64 | >64 | >64 | 3.9 |
| Ceftazidime-avibactam | ≤0.06/4 to >64/4 | 2/4 | >64/4 | 66.2 |
| Cefepime | ≤0.06 to >64 | >64 | >64 | 3.9 |
| Meropenem | 4 to >64 | 32 | >64 | 0.0 |
| Tigecycline | 0.125 to 8 | 1 | 4 | 87.0 |
| Citrobacter spp. (n = 22)d | ||||
| LYS228 | ≤0.06 to 2 | 0.5 | 2 | NA |
| Aztreonam | 0.12 to >64 | 64 | >64 | 27.7 |
| Ceftazidime | 0.5 to >64 | 64 | >64 | 27.3 |
| Ceftazidime-avibactam | ≤0.06/4 to >64/4 | 0.5/4 | 2/4 | 95.5 |
| Cefepime | ≤0.06 to >64 | 1 | >64 | 72.7 |
| Meropenem | ≤0.06 to >64 | ≤0.06 | 4 | 86.4 |
| Tigecycline | 0.25 to 2 | 0.5 | 2 | 100 |
| Enterobacter spp. (n = 40)e | ||||
| LYS228 | ≤0.06 to 4 | 0.5 | 2 | NA |
| Aztreonam | 0.25 to >64 | >64 | >64 | 17.5 |
| Ceftazidime | 0.25 to >64 | >64 | >64 | 15.0 |
| Ceftazidime-avibactam | 0.12/4 to >64/4 | 2/4 | >64/4 | 65.0 |
| Cefepime | ≤0.06 to >64 | 16 | >64 | 35.0 |
| Meropenem | ≤0.06 to >64 | 0.5 | 64 | 57.5 |
| Tigecycline | 0.25 to 8 | 1 | 4 | 77.5 |
| E. coli (n = 59) | ||||
| LYS228 | ≤0.06 to 16 | 0.12 | 1 | NA |
| Aztreonam | ≤0.06 to >64 | 0.25 | >64 | 59.3 |
| Ceftazidime | 0.12 to >64 | 0.5 | >64 | 62.7 |
| Ceftazidime-avibactam | ≤0.06/4 to >64/4 | 0.12/4 | >64/4 | 89.8 |
| Cefepime | ≤0.06 to >64 | 0.25 | >64 | 62.7 |
| Meropenem | ≤0.06 to >64 | ≤0.06 | 32 | 83.1 |
| Tigecycline | 0.12 to 1 | 0.25 | 0.5 | 100 |
| K. pneumoniae (n = 81) | ||||
| LYS228 | ≤0.06 to 64 | 0.25 | 1 | NA |
| Aztreonam | ≤0.06 to >64 | >64 | >64 | 27.2 |
| Ceftazidime | 0.12 to >64 | >64 | >64 | 25.9 |
| Ceftazidime-avibactam | ≤0.06/4 to >64/4 | 1/4 | >64/4 | 84.0 |
| Cefepime | ≤0.06 to >64 | 32 | >64 | 32.1 |
| Meropenem | ≤0.06 to >64 | 8 | 64 | 38.3 |
| Tigecycline | 0.12 to 8 | 1 | 4 | 86.4 |
| M. morganii (n = 14) | ||||
| LYS228 | ≤0.06 to 0.5 | ≤0.06 | 0.25 | NA |
| Aztreonam | ≤0.06 to 32 | 0.12 | 16 | 78.6 |
| Ceftazidime | 0.12 to 32 | 1 | 32 | 57.1 |
| Ceftazidime-avibactam | ≤0.06/4 to 1/4 | 0.12/4 | 0.5/4 | 100 |
| Cefepime | ≤0.06 to >64 | ≤0.06 | 0.5 | 92.9 |
| Meropenem | ≤0.06 to 0.5 | 0.12 | 0.25 | 100 |
| Tigecycline | 0.5 to 8 | 2 | 8 | 78.6 |
| P. mirabilis (n = 22) | ||||
| LYS228 | ≤0.06 to 0.12 | ≤0.06 | ≤0.06 | NA |
| Aztreonam | ≤0.06 to >64 | ≤0.06 | 2 | 90.9 |
| Ceftazidime | ≤0.06 to 32 | 0.25 | 8 | 81.8 |
| Ceftazidime-avibactam | ≤0.06/4 to 4/4 | ≤0.06/4 | 0.12/4 | 100 |
| Cefepime | ≤0.06 to >64 | 0.5 | >64 | 63.6 |
| Meropenem | 0.12 to 16 | 0.12 | 0.25 | 95.5 |
| Tigecycline | 1 to 8 | 4 | 8 | 36.4 |
| S. marcescens (n = 13) | ||||
| LYS228 | ≤0.06 to 4 | 0.12 | 1 | NA |
| Aztreonam | 0.12 to >64 | 2 | >64 | 69.2 |
| Ceftazidime | 0.12 to >64 | 1 | 32 | 61.5 |
| Ceftazidime-avibactam | 0.12/4 to >64/4 | 0.25/4 | 2/4 | 92.3 |
| Cefepime | ≤0.06 to >64 | 0.25 | >64 | 61.5 |
| Meropenem | ≤0.06 to 64 | 0.25 | 32 | 69.2 |
| Tigecycline | 0.5 to 8 | 1 | 2 | 92.3 |
| Salmonella spp. (n = 16) | ||||
| LYS228 | ≤0.06 to 1 | 0.12 | 1 | NA |
| Aztreonam | ≤0.06 to >64 | 0.25 | >64 | 56.3 |
| Ceftazidime | 0.25 to >64 | 0.5 | >64 | 56.3 |
| Ceftazidime-avibactam | 0.12/4 to 2/4 | 0.25/4 | 1/4 | 100 |
| Cefepime | ≤0.06 to >64 | 0.5 | >64 | 62.5 |
| Meropenem | ≤0.06 to 0.12 | <0.06 | 0.12 | 100 |
| Tigecycline | 0.25 to 2 | 0.5 | 1 | 100 |
a
Susceptibility was defined by CLSI document M100 (21). In the absence of CLSI breakpoints, U.S. FDA breakpoints were applied (30, 31).
b
NA, not applicable. Susceptibility has not been defined for LYS228.
c
Strains tested included C. freundii (n = 3), E. aerogenes (n = 1), E. cloacae (n = 11), E. hormaechei (n = 1), E. coli (n = 10), K. pneumoniae (n = 47), P. mirabilis (n = 1), and S. marcescens (n = 3).
d
Strains tested included C. freundii (n = 21) and C. koseri (n = 1).
e
Strains tested included E. aerogenes (n = 4), E. cloacae (n = 35), and E. hormaechei (n = 1).