TABLE 4.

Efficacies of ABT-773 and comparative agents in experimental H. influenzae-associated lung infections in rats

H. influenzae strain and compound	Daily dosed (mg/kg)	MIC (μg/ml)	Log10 CFU/lung (mean ± SEM)	Pf	ED50g (95% confidence limits)
					2-log10 reduction	3-log10 reduction
1435a
Vehicle controlc	NAh	NA	5.23 ± 0.40		NA	NA
ABT-773	5	0.5	6.38 ± 0.66	0.14	19.8 (15.8–24.8)	50.0 (35.6–70.3)
	20		3.19 ± 0.36	0.006
	60		1.91 ± 0.51	<0.001
Azithromycin	5	1	6.17 ± 0.61	0.21	55.4 (33.0–92.8)	70.3 (41.9–117.8)
	25		5.27 ± 1.08	0.97
	80		1.58 ± 0.65	<0.001
Clarithromycine	10	2	4.94 ± 0.35	0.65	109.8 (87.8–137.4)	>120 (NCi)
	40		6.15 ± 0.64	0.23
	120		2.81 ± 0.16	<0.001
3643b
Vehicle control	NA	NA	4.50 ± 0.38		NA	NA
ABT-773	5	2	4.86 ± 0.19	0.20	29.0 (28.7–29.2)	44.5 (44.1–44.8)
	20		3.08 ± 0.33	0.02
	60		0.50 ± 0.50	0.002
Azithromycin	5	1	4.57 ± 0.30	0.55	44.2 (44.0–44.5)	67.3 (67.0–67.7)
	25		3.33 ± 0.35	0.06
	80		0.95 ± 0.59	0.002
Clarithromycin	10	4	4.44 ± 0.30	0.89	67.8 (66.1–69.6)	101.4 (98.8–104.0)
	40		3.33 ± 0.43	0.06
	120		0.94 ± 0.58	0.002

^aIntratracheal inoculum of log₁₀ 7.8. 

^bIntratracheal inoculum of log₁₀ 8.6. 

^cVehicle-treated infected control rats were dosed orally for 3 days. 

^dRats were orally dosed daily for 3 days, starting 18 h postinfection. 

^eClarithromycin total daily dose given half strength 12 h apart. 

^fStatistical difference for comparison with result for untreated control, determined by the t test or Mann-Whitney U test. 

^gThe ED₅₀ (in milligrams per kilogram per day) to produce a 2- or 3-log₁₀ reduction in bacterial count compared to the vehicle-treated controls using linear regression of the group means. 

^hNA, not applicable. 

ⁱNC, not calculated.