TABLE 2.

Survival of mice treated with doses close to the ED₅₀s, given in one or two doses beginning 1 h after challenges^a

Organism	Drug regimen	Dosing regimen		No. of mice surviving/total no. of mice tested (%)	P value determined by Mantel-Haenszels testb	PK-PD parameters
		Dose (mg/kg)	No. of times given			Cmax/MIC	T>MIC (h)	AUCc/MIC (h)	Cmax-freed/MIC	T>MIC-freee (h)
S. aureus	Control	0		8/58 (13.8)		0.00	0.00	0.00	0.00	0.00
	Vancomycin	4.73	1	15/24 (62.5)	0.04	7.57	1.56	6.40	5.68	1.34
		2.37	2	9/24 (37.5)		4.07	2.04	6.40	3.05	1.60
	Teicoplanin	2.70	1	15/24 (62.5)	0.37	8.10	7.61	29.51	0.81	0.00
		1.35	2	11/24 (45.8)		4.24	10.18	29.51	0.42	0.00
S. pneumoniae	Control	0		0/20 (0.0)		0.00	0.00	0.00	0.00	0.00
	Vancomycin	0.67	1	17/30 (56.7)	<0.01	8.56	1.65	6.96	6.40	1.43
		0.33	2	5/30 (17.7)		4.56	2.22	6.96	3.44	1.80
	Teicoplanin	0.38	1	6/30 (20.0)	0.05	18.39	10.59	65.00	1.77	2.09
		0.19	2	4/30 (13.3)		9.68	16.14	65.00	0.97	0.00
	Teicoplanin	0.60	1	27/30 (90.0)	<0.01	29.03	12.25	104.52	2.90	3.88
		0.30	2	4/30 (13.3)		15.16	19.46	104.52	1.45	2.72

^aThe second doses were given 2 h later for vancomycin and 12 h later for teicoplanin. Mice were observed for 6 days. 

^bComparison of the survival curves for the two regimens with the same total dose. Two-tailed P values are given. 

^cThe baseline used in the calculation of the AUC was 0.01 μg/ml. 

^dThe free fractions of the peak serum drug concentrations are indicated. 

^eThe time for which the free fractions of the drugs in serum were above the MICs.