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studied. Aerosol therapy in mice is problematic due to the high cost of the required apparatus. The purpose of this study was to explore the efficacy of intranasal (IN) administration (as a surrogate for aerosol delivery) of isoniazid (INH) and rifalazil (RZL) in a murine tuberculosis model compared to oral delivery.Methods & Materials: Six week old female Balb/c mice (purchased from Charles River Laboratories, Wilmington, MA) were infected intranasally with about 10 3 CFU of Mycobacterium tuberculosis (MTB) ATCC 27294 (H37Rv) for experiment 1 or about 10 6 CFU of MTB ATCC 35801 (Erdman) for experiment 2. One week post infection mice in experiment 1 were treated with INH 5mg/kg orally by gavage or 5mg/kg IN for 3 days and mice in experiment 2 were treated with RZL 5 mg/kg orally by gavage 5 days/week or 5 mg/kg IN Mon, Wed, and Fri for 2 weeks. At the initiation of therapy in each experiment a group of mice (early controls) were euthanized by CO 2 inhalation and their lungs were collected. At the completion of therapy an untreated group of mice, late controls (LC), and treated mice were euthanized. Mycobacterial loads in right lungs were measured by serial dilution and plating on Middlebrook 7H10 agar plates.Results: The mycobacterial loads (log CFU) for the EC, LC, INH oral and INH IN were 3.34, 4.49, 2.94, and 2.82 respectively (exp. 1). The mycobacterial loads for the EC, LC, RZL oral, and RZL IN were 6.26, 8.93, 4.30, and 4.58 respectively (exp. 2). The LC group was euthanized 3 days early due to their advanced illness. IN delivery of INH and RIF was significantly better than the untreated late controls. Conclusion: The activities of INH and RZL by IN delivery in these experiments suggest that other agents that cannot be given orally could be evaluated for their potential therapeutic activities by IN administration. http://dx.Background: Mycobacterium tuberculosis (MTB) is an important cause of bacteremia and sepsis in HIV patients residing in sub-Saharan Africa. Many patients with MTB sepsis go undiagnosed and die within 18 days of presentation, making culture inadequate for detecting MTB in the blood. Objective:To determine the feasibility of ambient temperature transport of blood in PrimeStore MTM ® to a distant lab for real-time PCR detection of MTB bacteremia and to monitor clearance of MTB from the blood after therapy.Methods & Materials: BALB/c female mice were injected intravenously with 0.2 mls of ethanol killed MTB (approximately 10 5

2 weeks. At the initiation of therapy in each experiment a group of mice (early controls) were euthanized by CO 2 inhalation and their lungs were collected. At the completion of therapy an untreated group of mice, late controls (LC), and treated mice were euthanized. Mycobacterial loads in right lungs were measured by serial dilution and plating on Middlebrook 7H10 agar plates.Results: The mycobacterial loads (log CFU) for the EC, LC, INH oral and INH IN were 3.34, 4.49, 2.94, and 2.82 respectively (exp. 1). The mycobacterial loads for the EC, LC, RZL oral, and RZL IN were 6.26, 8.93, 4.30, and 4.58 respectively (exp. 2). The LC group was euthanized 3 days early due to their advanced illness. IN delivery of INH and RIF was significantly better than the untreated late controls. Conclusion: The activities of INH and RZL by IN delivery in these experiments suggest that other agents that cannot be given orally could be evaluated for their potential therapeutic activities by IN administration.