TECHNOLOGY AREAS: Biomedical

OBJECTIVE: Novel approaches and novel antibacterial agents are sought for the treatment of bacterial pathogens that are problematic for military personnel.

DESCRIPTION: The discovery of greater than 100 antibiotics from the 1940s-1970s suggested that infectious diseases could be easily cured, and the possibility that many infectious diseases might even be eliminated. However, bacteria quickly learned to withstand the effects of antibiotics and today bacterial infections that are resistant to all conventional antibiotics are common in hospital and military settings.1 New antibacterial agents are needed that are based on novel approaches that will combat antibiotic resistance.2 Offerors are asked to focus their efforts on a military relevant pathogen (e.g. Acinetobacter baumannii (wound infections)3,4, community acquired methicillin resistant Staphylococcus aureus5,6, Coxiella burnetti (causative agent of "Q fever")7,8 diarrheagenic Eschericia coli9, or Pseudomonas aeruginosa.10). Systemic, topical, and prophylactic measures are sought.

PHASE I: Identify lead compounds that function as novel antibacterials.

PHASE II: Subject promising antibacterial candidates to initial testing for efficacy and toxicology in laboratory animals.

PHASE III: Continue the program forward and address Food and Drug Administration regulatory matters to reach full drug development.

PRIVATE SECTOR COMMERCIAL POTENTIAL/DUAL-USE APPLICATIONS: New antibacterial agents would have applicability in military and civilian medical care.

REFERENCES:
1. Taubes, G. "The Bacteria Fight Back" Science, Vol. 321, pp. 356-361 (2008).

2. Smith, P. A. and Romesberg, F. E. "Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation." Nature Chemical Biology, Vol. 3, pp. 549-556 (2007).

3. Hawley, J. S., Murray, C. K., Griffith, M. E., McElmeel, M. L., Fulcher, L. C. Hospenthal, D. R., Jorgensen, J. H. "Susceptibility of acinetobacter strains isolated from deployed U.S. military personnel" Antimicrob. Agents Chemother., Vol. 51, pp. 376-378 (2007).

4. Sebeny, P. J., Riddle, M. S., Petersen, K. "Acinetobacter baumannii skin and soft-tissue infection associated with war trauma" Clin. Infect Dis., Vol. 47, pp. 444-449 (2008).

5. Zinderman, C. E., Conner, B., Malakooti, M. A., LaMar, J. E., Armstrong, A., Bohnker, B. K. "Community-acquired methicillin-resistant Staphylococcus aureus among military recruits" Emerg. Infect. Dis., Vol 10, pp. 941-944 (2004).

6. Pagac, B. B., Reiland, R. W., Bolesh, D. T., Swanson, D. L. "Skin lesions in barracks: consider community-acquired methicillin-resistant Staphylococcus aureus infection instead of spider bites" Mil. Med., Vol. 171, pp. 830-832 (2006).

7. Hartzell, J. D., Peng, S. W., Wood-Morris, R. N., Sarmiento, D. M, Collen, J.F., Robben, P. M., Moran, K. A. "Atypical Q fever in US soldiers" Emerg. Infect. Dis., Vol. 13, pp. 1247-1249 (2007).

8. Faix, D. J., Harrison, D. J., Riddle, M. S., Vaughn, A. F., Yingst, S. L., Earhart, K. Thibault, G. "Outbreak of Q fever among US military in western Iraq, June-July 2005" Clin. Infect. Dis., Vol. 46, e65-8 (2008).

9. Sanders, J. W., Frenck, R. W., Putnam, S. D., Riddle, M. S., Johnston, J. R., Ulukan, S., Rockabrand, D. M., Monteville, M. R. Tribble, D. R. "Azithromycin and loperamide are comparable to levofloxacin and loperamaide for the treatment of traveler�s diarrhea in United States military personnel in Turkey" Clin. Infect. Dis., Vol. 45, pp. 294-301 (2007).

10. Ressner, R. A., Murray, C. K., Griffith, M. E., Rasnake, M. S., Hospenthal, D. R., Wolf, S. E. "Outcomes of bacteremia in burn patients involved in combat operations overseas" J. Am. Coll. Surg., Vol. 206, pp. 439-444 (2008).

KEYWORDS: antibacterials; antibiotics; antibiotic resistance; antimicrobials; multi-drug resistance; infectious disease