Testing and Assessment of Antibacterial Compounds

THIS IS A NOTICE TO INTENT TO AWARD A SOLE SOURCE CONTRACT AND IS NOT A REQUEST FOR COMPETITIVE PROPOSALS. The U.S. Army Medical Research Acquisition Activity (USAMRAA) intends to award a sole source basis in accordance with FAR 6.302-1 to the University of Virginia (UVA) in Charlottesville, VA. They are the only responsible source that can provide the testing and evaluation of a proprietary antibacterial compound and compound derivatives in specialized murine in vivo models developed specifically by the University. This requirement is in support of the Wound Infections Department (WID) within the Bacterial Diseases Branch (BDB) at the Walter Reed Army Institute of Research (WRAIR) located in Silver Spring, Maryland. Objectives: The contractor shall test and evaluate CT-AP1 and derivatives in mouse lung models using pharmacokinetics (PK), colony forming units (CFU), survival and calcineurin activity assessment. PK studies of CT-AP1 will be performed in normal and disease tissues using the murine K. pneumoniae infection (sepsis) lung model. The PK studies will inform design of CT-AP1 derivatives that promote favorable ADME properties. PK studies will also be performed using the best optimized derivatives. The best optimized derivative will be selected based upon favorable cytotoxicity, metabolic stability & permeability assay results. For PK studies in brief, CT-AP1 and derivative compounds will be tested in mice, following 2 different routes of administration: IV or IP, at a dose of 2 mg/kg for IV and 10mg/kg for IP route. Blood will be collected at times 0, 0.1, 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours. Samples will be analyzed using LC-MS/MS to determine the basic PK constants (T1/2, Tmax, Co, bioavailability, AUClast, AUCinf, CL, Vss, MRTlast) of the compounds. To assess CFU burden in the lungs, mice will be humanely euthanized on Days 2 and 3 post-infection, lungs will be homogenized in PBS followed by serial dilutions plated using the Autoplate® Spiral Plating System onto LB agar. Bacterial load will be reported as CFU per gram of lung tissue. Efficacy will be determined by animal survival, and measurement of the reduction of CFUs from the organs harvested (lungs) and CFU reduction in peripheral blood.