TABLE 4.

Kill kinetics of LYS228 and comparators against E. coli and K. pneumoniae strains expressing various β-lactamases

Organism (β-lactamase) and test agent	MIC (μg/ml)	Concentration tested (μg/ml)	Δlog10 CFU/ml at:
			2 h	4 h	8 h	24 h
E. coli ATCC 25922
LYS228	0.25	0.5	−2.0	−4.6	−4.1	2.0
		1	−2.2	−4.6	−4.6	−4.6
		2	−2.1	−4.6	−4.6	−4.6
Aztreonam	0.12	0.25	−2.1	−3.8	−3.8	−4.4
		1	−1.7	−4.1	−4.4	−4.4
Meropenem	0.03	0.06	−1.6	−3.8	−4.4	−4.4
		0.25	−3.6	−4.1	−4.4	−4.4
E. coli ATCC 35218 (TEM-1)
LYS228	0.06	0.12	−2.8	−3.8	−4.6	−4.9
		0.25	−2.8	−4.1	−4.9	−4.9
		0.5	−2.9	−3.9	−4.1	−4.9
Meropenem	0.03	0.06	−2.2	−2.9	−4.1	−4.1
		0.25	−2.5	−3.0	−4.1	−4.1
E. coli NB27235 (CTX-M-15)
LYS228	0.25	0.5	−3.0	−3.1	−4.1	−4.8
		1	−3.1	−3.2	−4.2	−4.5
		2	−3.5	−3.4	−4.2	−4.8
Meropenem	0.03	0.06	−3.0	−3.6	−1.7	3.7
		0.25	−3.3	−4.1	−4.8	−4.8
E. coli NB27169 (KPC-3)
LYS228	0.5	1	−0.2	−2.1	−2.6	−4.2
		2	−1.0	−2.2	−2.9	−4.9
		4	−1.2	−2.0	−2.9	−4.3
E. coli NB27236 (NDM-1)
LYS228	4	8	−4.4	−4.4	−4.4	−2.1
		16	−2.9	−4.1	−4.4	−4.4
		32	−4.4	−3.9	−4.4	−4.4
K. pneumoniae ATCC 43816
LYS228	0.06	0.12	−0.7	−1.9	−0.9	2.7
		0.25	−1.0	−1.7	−3.2	−4.6
		0.5	−1.1	−2.1	−3.3	−4.6
Aztreonam	0.06	0.12	−0.6	−2.0	−0.5	0.7
		0.5	−0.3	−2.1	−3.3	−4.6
Meropenem	0.06	0.12	−2.3	−4.9	−4.9	−4.9
		0.5	−3.0	−4.9	−4.9	−4.9
K. pneumoniae NB29254 (SHV-1)
LYS228	0.12	0.25	−1.7	−2.6	−4.9	−1.4
		0.5	−1.9	−2.9	−4.9	−4.9
		1	−1.7	−2.7	−4.9	−4.9
Meropenem	0.03	0.06	−2.3	−3.4	−4.9	−1.8
		0.25	−2.8	−3.7	−4.9	−4.9
K. pneumoniae NB29084 (CTX-M-14)
LYS228	0.5	1	−0.3	−1.5	−2.7	−4.9
		2	−0.9	−2.0	−3.2	−4.9
		4	−0.8	−2.4	−3.7	−4.9
Meropenem	0.03	0.06	−1.4	−2.8	−0.7	4.0
		0.25	−3.2	−3.5	−1.6	3.9
K. pneumoniae NB29082 (KPC-2)
LYS228	0.5	1	−1.4	−2.4	−4.5	−5.0
		2	−1.6	−2.5	−4.2	−5.0
		4	−1.6	−2.8	−4.1	−5.0
K. pneumoniae ATCC 1100975 (NDM-1)
LYS228	1	2	−2.0	−1.9	−3.8	−5.0
		4	−1.9	−2.9	−4.1	−5.0
		8	−2.0	−1.6	−4.5	−5.0