TABLE 5.
In vitro activity of meropenem plus xeruborbactam at 4 and 8 µg/mL and comparator BLI combination agents and comparator BLI combination agents against carbapenem-resistant strains of Enterobacterales with either partially functional or non-functional OmpK36 according to carbapenemase production a
| MEM + XER (4) | MEM + XER (8) | FEP + TAN (4) | CAZ + AVI (4) | MEM + VAB (8) | IMP + REL (4) | |
|---|---|---|---|---|---|---|
| PFN b OmpK36 | N = 137 | |||||
| MIC50 | 0.25 | 0.125 | 2 | 4 | 16 | 2 |
| MIC90 | 8 | 2 | 32 | >64 | >64 | >64 |
| % Inhibited c | 91.2 | 98.5 | 80.3 | 68.6 | 49.6 | 47.4 |
| Non-functional (NF) b OmpK36 | N = 62 | |||||
| MIC50 | 0.5 | 0.25 | 2 | 4 | 8 | 4 |
| MIC90 | 16 | 2 | 8 | >64 | >64 | >64 |
| % Inhibited | 83.9 | 96.8 | 90.3 | 67.7 | 61.3 | 24.2 |
| PFN + NF MBL negative | N = 154 | |||||
| MIC50 | 0.25 | 0.125 | 2 | 2 | 4 | 1 |
| MIC90 | 4 | 0.5 | 8 | 16 | 64 | 8 |
| % Inhibited | 92.90 | 100.00 | 98.10 | 88.30 | 68.20 | 51.90 |
| PFN + NF KPC | N = 118 | |||||
| MIC50 | 0.25 | 0.125 | 2 | 4 | 2 | 1 |
| MIC90 | 8 | 0.5 | 8 | 16 | 64 | 8 |
| % Inhibited | 91.50 | 100.00 | 97.50 | 84.70 | 78.80 | 63.60 |
| PFN + NF OXA-48-like | N = 31 | |||||
| MIC50 | 0.125 | ≤0.06 | 2 | 2 | 32 | 4 |
| MIC90 | 0.25 | 0.25 | 8 | 4 | 64 | 64 |
| % Inhibited | 100.00 | 100.00 | 100.00 | 100.00 | 22.60 | 3.20 |
| PFN + NF all MBLs | N = 45 | |||||
| MIC50 | 4 | 1 | 32 | >64 | >64 | >64 |
| MIC90 | 64 | 8 | >64 | >64 | >64 | >64 |
| % Inhibited | 75.60 | 91.10 | 33.30 | 0.00 | 2.20 | 0 |
| PFN + NF NDM | N = 29 | |||||
| MIC50 | 8 | 2 | 32 | >64 | >64 | >64 |
| MIC90 | 64 | 16 | >64 | >64 | >64 | >64 |
| % Inhibited | 68.90 | 86.20 | 31.00 | 0.00 | 0.00 | 0.00 |
| PFN + NF VIM | N = 13 | |||||
| MIC50 | 2 | 0.25 | 16 | >64 | >64 | >64 |
| MIC90 | 8 | 1 | 32 | >64 | >64 | >64 |
| % Inhibited | 92.30 | 100.00 | 46.20 | 0.00 | 0.00 | 0.00 |
AVI, avibactam; CAZ, avibactam; FEP, cefepime; IMP, imipenem; MEM, meropenem; NF, non-functional; PFN, partially functional; REL, relebactam; TAN, taniborbactam; VAB, vaborbactam; XER, xeruborbactam.
OmpK36 was considered PFN if it contained a duplication of two amino acids, Gly134Asp135 (GD repeat) located within the L3 internal loop, resulting in the constriction of the channel; OmK36 was considered NF if it contained frameshift, nonsense mutations and large insertions, or reduced expression due to insertions in the promoter region has been identified.
% Inhibited at the following concentrations: meropenem/xeruborbactam: ≤8/4 and ≤8/8 µg/mL; cefepime/taniborbactam: ≤8/4; ceftazidime-avibactam : ≤8/4 µg/mL (FDA susceptible breakpoint); imipenem/relebactam: ≤1/4 µg/mL (FDA susceptible breakpoint); meropenem/vaborbactam: ≤8/8 µg/mL (European Medicines Agency susceptible breakpoint). BLI concentrations are in brackets.