TABLE 5.

In vitro activity (MIC₅₀/MIC₉₀ and % inhibited) of meropenem alone and combined with QPX7728 at 4 and 8 μg/ml and comparator BLI combination agents against carbapenem resistant strains of Enterobacterales according to the functional status of OmpK35/OmpF and OmpK36/OmpC and carbapenemase present.

	Meropenem-QPX7728 at 4 μg/ml	Meropenem-QPX7728 at 8 μg/ml	Meropnem-vaborbactam at 8 μg/ml	Ceftazidime-avibactamat 4 μg/ml	Imipenem-relebactam at 4 μg/ml
K. pneumonia KPC (N = 230)
OmpK36-defective (N = 135)	0.25/2	0.125/0.5	2/32	4/16	0.5/4
% Inhibited	94.8%	100.0%	72.6%	88.1%	70.4%
OmpK36-functional (N = 95)	≤0.06/0.125	≤0.06/≤0.06	≤0.06/0.25	2/8	0.25/1
% Inhibited*	100.0%	100.0%	97.9%	91.6%	94.7%
MBL (N = 177)
OmpK36-defective (N = 42)	4/32	1/4	>64/>64	>64/>64	>64/>64
% Inhibited	81.0%	92.9%	0.0%	0.0%	0.0%
OmpK36-functional (N = 135)	≤0.06/0.5	≤0.06/0.125	32 > 64	>64/>64	32>64
% Inhibited	99.3%	99.3%	20.0%	2.2%	3.7%

*: % inhibited at the following concentrations: meropenem-QPX7728: ≤ 8/4 μg/ml and ≤ 8/8 (PK-PD susceptible breakpoint); meropenem-vaborbactam: ≤ 4/8 μg/ml (FDA susceptible breakpoint); ceftazidime-avibactam: ≤ 8/4 μg/ml (FDA susceptible breakpoint); imipenem-relebactam: ≤ 1/4 μg/ml (FDA susceptible breakpoint). Frame-shift and nonsense mutations, insertions of IS elements in the structural part or in a promoter sequence, small amino-acid insertions constricting the channel were identified as mutations resulting in a defective protein. In the absence of these mutations, OmpK36 was assumed to be functional. Data from Nelson et al. (2020a).