TABLE 4.

Treatment of SF100 S. mitis-oralis strain with ascending dosages of DAP in combination of CRO versus DAP and CRO alone in in vivo IE model^a

Treatment (no. of animals)	Vegetation [sterile] (/ = Growth on DAP 2 mg/L plates)b	Kidney	Spleen
Untreated Controls (8)	7.93 ± 0.57	4.58 ± 0.52	4.70 ± 0.85
DAP 4 mg/kg i.v. once daily × 4 days (6)	7.80 ± 0.81/1.00 ± 0.06c	3.50 ± 0.49c	3.54 ± 0.28c
DAP 6 mg/kg (6)	7.42 ± 1.08/3.53 ± 2.63d	4.51 ± 0.63	4.45 ± 0.49
DAP 8 mg/kg (6)	7.69 ± 0.75/4.30 ± 2.78e	3.24 ± 0.41e	3.40 ± 0.90e
DAP 10 mg/kg (6)	7.51 ± 0.80/5.72 ± 1.98f	3.41 ± 0.63f	3.64 ± 0.84f
DAP 12 mg/kg (6)	7.01 ± 1.07/4.28 ± 2.57g	3.86 ± 0.76	3.64 ± 0.79g
DAP 18 mg/kg (6)	7.25 ± 0.84/5.74 ± 1.28	4.42 ± 0.78	4.77 ± 0.45
CRO 40 mg/kg i.v. once daily × 4 days (6)	5.68 ± 0.93 [0/6]h	0.95 ± 0.41 [5/6]h	1.13 ± 0.48 [5/6]h
DAP (4 mg/kg) + CRO (6)	3.75 ± 1.59 [1/6]i,j,k	0.76 ± 0.07 [6/6]i,j	0.89 ± 0.12 [6/6]i,j
DAP (8 mg/kg) + CRO (7)	0.89 ± 0.19 [7/7]l,m,n	0.92 ± 0.11 [7/7]m,n	0.92 ± 0.08 [7/7]m,n

^aStatistical differences for Untreated controls versus DAP 4, 6, 8, 10, 12 mg/kg; Untreated controls versus CRO alone; Untreated controls versus DAP + CRO; combination of DAP + CRO versus DAP alone; combination of DAP + CRO versus CRO alone were determined by Student's t test.

^bThese designations define the number of sterile target tissues/number sampled (e.g., 6/6 = all 6 target tissues were sterilized), as well as the proportion of vegetations having DAP-R subpopulations as defined by growth on DAP plates (2 mg/L).

^cP < 0.01 untreated controls versus DAP 4 mg/kg.

^dP < 0.01 untreated controls versus DAP 6 mg/kg.

^eP < 0.05 untreated controls versus DAP 8 mg/kg.

^fP < 0.05 untreated controls versus DAP 10 mg/kg.

^gP < 0.05 untreated controls versus DAP 12 mg/kg.

^hP < 0.001 untreated controls versus CRO alone.

ⁱP < 0.001 DAP 4 mg/kg + CRO versus DAP 4 mg/kg.

^jP < 0.001 untreated controls versus DAP 4 mg/kg + CRO.

^kP < 0.05 DAP 4 mg/kg + CRO.

^lP < 0.0001 DAP 8 mg/kg + CRO. Parenthesis () = number of rabbits.

^mP < 0.00001 untreated controls versus DAP 8 mg/kg + CRO.

ⁿP < 0.01 DAP 8 mg/kg + CRO versus DAP 8 mg/kg.