Antistaphylococcal Activity of CB-181963 (CAB-175), an Experimental Parenteral Cephalosporin | Antimicrobial Agents and Chemotherapy

DOI: 10.1128/AAC.48.10.4037-4039.2004

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FIG. 1.
CB-181963 chemical structure.

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TABLE 1.

MICs (in micrograms per milliliter) for 265 S. aureus strains

Drug	Methicillin susceptible (n = 66)			Methicillin resistant (n = 199)
Drug	Range	MIC₅₀	MIC₉₀	Range	MIC₅₀	MIC₉₀
CB-181963	≤0.12-1	0.5	1	0.5-4	2	4
Vancomycin	0.5-4	1	2	0.5-256	1	2
Teicoplanin	0.25-16	1	2	≤0.12-128	0.5	1
Linezolid	≤0.25-2	2	2	0.5-2	2	2
Ranbezolid	≤0.25-4	2	4	0.5-8	2	4
Tigecycline	≤0.06-1	0.25	0.5	≤0.06-1	0.25	0.25
Quinupristin- dalfopristin	0.12-1	0.25	0.5	≤0.06-1	0.5	0.5
Levofloxacin	0.12->32	8	32	0.12->32	8	>32

TABLE 2.
MICs of available compounds active against VISA and VRSA strains
Drug MIC (μg/ml) for strain^a:
NRS1 NRS12 NRS17 NRS56 NRS63 VRS1 VRS2
CB-181963 4 1 4 2 1 4 4
Linezolid 1 2 2 0.5 2 1 1
Quinupristin-dalfopristin 0.5 0.25 0.5 0.5 0.25 0.25 0.25
Daptomycin^b 2.0 2.0 2.0 2.0 1.0 0.5 0.25
↵a NARSA repository numbers are used for strain designations.
↵b Values for daptomycin are from reference 2 and unpublished results.

TABLE 3.

MICs for six S. aureus strains tested by time kill

Drug	MIC (μg/ml) for strain no:
Drug	1^a	2^a	3^a	4^a	5^b	6^c
CB-181963	2.0	2.0	4.0	2.0	4.0	2.0
Vancomycin	1.0	1.0	1.0	1.0	4.0	32
Teicoplanin	0.5	1.0	0.25	1.0	4.0	8.0
Linezolid	2.0	4.0	4.0	4.0	1.0	4.0
Ranbezolid	2.0	4.0	4.0	2.0	1.0	2.0
Tigecycline	0.25	0.25	0.5	0.25	0.25	0.125
Quinupristin-dalfopristin	0.5	0.5	0.5	0.5	0.5	0.5
Levofloxacin	32	64	16	8	16	32

↵a Methicillin resistant.
↵b Vancomycin intermediate.
↵c Vancomycin resistant.

TABLE 4.

Time-kill results of six S. aureus strains

Drug and concn	No. of strains killed at time point^a:
	3 h			6 h			12 h			24 h
	−1	−2	−3	−1	−2	−3	−1	−2	−3	−1	−2	−3
CB-181963
4× MIC	0	0	0	6	1	0	6	5	4	6	6	6
2× MIC	0	0	0	5	1	0	6	5	3	6	6	5
MIC	0	0	0	5	1	0	6	4	3	2	2	2
Vancomycin
4× MIC	1	0	0	2	1	0	6	2	1	6	6	3
2× MIC	1	0	0	2	0	0	6	2	1	6	5	3
MIC	0	0	0	2	0	0	6	1	0	5	4	2
Teicoplanin
4× MIC	1	0	0	4	1	0	6	4	1	6	4	2
2× MIC	1	0	0	3	1	0	6	4	1	6	3	1
MIC	1	0	0	2	1	0	6	3	1	4	2	1
Linezolid
4× MIC	0	0	0	0	0	0	0	0	0	3	0	0
2× MIC	0	0	0	0	0	0	0	0	0	3	0	0
MIC	0	0	0	0	0	0	0	0	0	0	0	0
Ranbezolid
4× MIC	0	0	0	0	0	0	1	0	0	2	0	0
2× MIC	0	0	0	0	0	0	1	0	0	1	0	0
MIC	0	0	0	0	0	0	0	0	0	0	0	0
Tigecycline
4× MIC	0	0	0	0	0	0	0	0	0	2	0	0
2× MIC	0	0	0	0	0	0	0	0	0	1	0	0
MIC	0	0	0	0	0	0	0	0	0	1	0	0
Quinupristin- dalfopristin
4× MIC	0	0	0	1	0	0	1	0	0	6	1	0
2× MIC	0	0	0	1	0	0	1	0	0	3	1	0
MIC	0	0	0	1	0	0	1	0	0	2	1	0
Levofloxacin
4× MIC	1	0	0	4	4	0	6	4	3	6	5	4
2× MIC	1	0	0	4	3	0	6	4	3	6	5	3
MIC	1	0	0	3	3	0	6	4	3	6	4	1

↵a −1, 90% killing; −2, 99% killing; −3, 99.9% killing.

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