TABLE 1.
Inhibitory activity of TACN and MEM alone and in combination against reference strains of CREa
| Enzyme produced and bacterial species | Metallo-β-lactamase produced (class B) | MIC (mg/liter) |
MBC (mg/liter) of MEM-TACN8 | MBC/MIC ratio of MEM-TACN8 | MEM-TACN8 MIC (mg/liter) with serum | FIC index | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| MEM alone | TACN alone | {MEM-TACN4} | {MEM-TACN8} | {MEM-TACN16} | ||||||
| Metallo-β-lactamases | ||||||||||
| E. coli | NDM-1 | 128 | 1,024 | {0.125–4} | {0.125–8} | {0.06–16} | 0.5 | 4 | 0.25 | 0.008 |
| E. cloacae | NDM-1 | 16 | >1,024 | {0.06–4} | {0.03–8} | 0.125 | 4 | 0.125 | ≤0.005 | |
| Citrobacter freundii | NDM-1 | 8 | 1,024 | {0.25–4} | {0.125–8} | {0.125–16} | 0.125 | 1 | 0.25 | 0.023 |
| Providencia rettgeri | NDM-1 | 64 | >1,024 | {8–4} | {2–8} | 2 | 1 | 2 | ≤0.035 | |
| Providencia stuartii | NDM-1 | 16 | >1,024 | {2–4} | {2–8} | 2 | 1 | 4 | ≤0.253 | |
| E. coli | NDM-4 | 128 | 1,024 | {0.125–8} | {0.06–16} | 0.125 | 1 | 1 | 0.008 | |
| E. coli | VIM-1 | 32 | 1,024 | {0.25–4} | {0.125–8} | {0.06–16} | 0.125 | 1 | 0.25 | 0.011 |
| K. pneumoniae | VIM-1 | 32 | 512 | {2–4} | {0.125–8} | {0.06–16} | 0.5 | 4 | 8 | 0.019 |
| E. cloacae | VIM-1 | 8 | 128 | {1–4} | {1–8} | 1 | 1 | 2 | 0.187 | |
| E. coli | VIM-2 | 8 | 128 | {0.06–4} | {0.03–8} | 0.06 | 2 | 0.125 | 0.066 | |
| E. cloacae | IMP-1 | 32 | 512 | {0.25–4} | {0.125–8} | 0.5 | 4 | 2 | 0.019 | |
| K. pneumoniae | IMP-1 | 32 | 512 | {8–4} | {4–8} | 4 | 1 | 16 | 0.141 | |
| E. coli | IMP-1 | 16 | 512 | {1–4} | {0.06–8} | {0.03–16} | 0.125 | 2 | 0.25 | 0.019 |
| E. cloacae | IMP-8 | 8 | 512 | {0.5–4} | {0.125–8} | {0.03–16} | 0.25 | 2 | 0.125 | 0.031 |
| K. pneumoniae | IMP-8 | 16 | 1,024 | {8–4} | {4–8} | {2–16} | 8 | 2 | 4 | 0.250 |
| {MEM-TACN8} | {MEM-TACN16/32} | {MEM-TACN64} | ||||||||
| Serine-β-lactamases | ||||||||||
| K. pneumoniae | OXA-48 | 8 | 128 | {8–8} | {8–16} | {4–64} | NA | NA | NA | NA |
| E. cloacae | KPC-2 | 32 | 256 | {32–32} | {32–64} | NA | NA | NA | NA | |
| ATCC susceptible strains | ||||||||||
| K. pneumoniae ATCC BAA 1706 |
Susceptible strain | 0.5 | 1,024 | NE | NA | NA | NA | NA | ||
| E. coli ATCC 25922 | Susceptible strain | 0.03 | 1,024 | NE | NA | NA | NA | NA | ||
a
TACN4, TACN8, TACN16, TACN32, and TACN64 represent a fixed concentration of 4, 8, 16, 32, and 64 mg/liter TACN, respectively, with various concentrations of meropenem; (in the braces, the first number represents the MIC for MEM and the second number represents the given TACN concentration); NA, not applicable; NE, no inhibitory effect.