TABLE 4.

Protective effect of CS-023 on systemic infections in mice

Organism (MIC of drug), Challenge dose (CFU/mouse)	Compound	MIC (μg/ml)	ED50a (mg/kg/dose)	95% confidence interval (mg/kg/dose)
Methicillin-susceptible S. aureus Smithb (MIC of MPIPC,d 0.25 μg/ml), 1.3 × 107	CS-023	0.12	0.97	0.61-1.5
	Imipenem/cilastatin	0.016	0.20	NCc
	Meropenem	0.06	5.8	3.9-9.9
	Ceftriaxone	4	6.6	NC
Methicillin-susceptible S. aureus 560b (MIC of MPIPC, 1 μg/ml), 1.3 × 108	CS-023	0.25	2.6	1.6-4.3
	Imipenem/cilastatin	0.016	0.61	0.40-0.99
	Meropenem	0.12	39	27-58
	Ceftriaxone	4	8.8	NC
Methicillin-resistant S. aureus 507b (MIC of MPIPC, 32 μg/ml), 1.6 × 107	CS-023	1	7.9	3.9-12
	Imipenem/cilastatin	0.12	13	8.6-20
	Meropenem	2	>100	NC
	Ceftriaxone	32	39	25-70
Methicillin-susceptible S. epidermidis 1392,b 4.8 × 108	CS-023	0.06	0.76	0.47-1.1
	Imipenem/cilastatin	0.016	0.16	0.10-0.24
	Meropenem	0.06	5.8	3.5-9.7
	Ceftriaxone	2	11	NC
Penicillin-susceptible S. pneumoniae 2132b (MIC of PCG,e 0.016 μg/ml), 1.4 × 102	CS-023	≤0.008	0.10	0.071-0.16
	Imipenem/cilastatin	≤0.008	0.042	0.010-0.075
	Meropenem	0.016	1.1	0.69-2.0
	Ceftriaxone	0.016	0.13	0.083-0.19
	Ampicillin	0.03	0.48	0.30-0.74
Penicillin-resistant S. pneumoniae 9605b (MIC of PCG, 4 μg/ml), 6.9 × 102	CS-023	0.25	0.55	0.38-0.79
	Imipenem/cilastatin	0.25	0.33	0.13-0.52
	Meropenem	0.5	3.9	2.0-6.4
	Ceftriaxone	1	2.1	1.2-4.9
	Ampicillin	4	7.9	4.9-14
E. coli 704, 5.9 × 107	CS-023	≤0.008	1.2	0.82-2.5
	Imipenem/cilastatin	0.12	4.9	3.3-10
	Meropenem	0.016	5.9	NC
	Ceftazidime	0.12	3.2	NC
	Ceftriaxone	0.03	0.33	0.19-0.63
C. freundii 1231,b 3.7 × 107	CS-023	0.016	0.31	0.17-0.54
	Imipenem/cilastatin	1	1.2	0.81-1.8
	Meropenem	0.016	1.2	0.41-2.0
	Ceftazidime	0.5	3.2	1.7-5.4
	Ceftriaxone	0.12	0.27	0.15-0.55
K. pneumoniae 866,b 6.4 × 106	CS-023	0.016	0.67	0.46-1.0
	Imipenem/cilastatin	0.25	1.8	1.2-2.7
	Meropenem	0.03	1.8	1.1-3.0
	Ceftazidime	0.25	0.46	0.29-0.79
	Ceftriaxone	0.25	0.11	NC
E. aerogenes 100,b 4.6 × 107	CS-023	0.06	6.5	3.2-15
	Imipenem/cilastatin	2	3.1	1.7-5.0
	Meropenem	0.06	31	NC
	Ceftazidime	0.12	3.1	1.5-5.0
	Ceftriaxone	0.06	2.5	NC
S. marcescens 1850, 6.9 × 107	CS-023	0.016	1.1	0.61-6.7
	Imipenem/cilastatin	0.12	9.4	4.8-74
	Meropenem	0.016	2.5	1.6-5.0
	Ceftazidime	0.12	0.68	0.32-25
	Ceftriaxone	0.25	0.054	0.030-55
P. mirabilis 1262,b 4.8 × 108	CS-023	0.25	39	22-260
	Imipenem/cilastatin	4	>100	NC
	Meropenem	0.12	>100	NC
	Ceftazidime	0.25	29	19-43
	Ceftriaxone	0.016	0.28	0.18-0.45
P. aeruginosa 1008, 2.0 × 107	CS-023	0.12	0.95	0.42-4.8
	Imipenem/cilastatin	1	0.73	0.50-1.1
	Meropenem	0.12	4.2	2.7-12
	Ceftazidime	2	58	38-110
	Ceftriaxone	128	>100	NC

^aGroups of seven mice were challenged with bacterial suspension intraperitoneally, and the compounds were administered by the subcutaneous route immediately and 4 h postinfection.

^b5% mucin.

^cNC, not calculated.

^dMPIPC, oxacillin.

^ePCG, penicillin G.