7th Annual BMRP Investigator Meeting - Abstract

 

Manju Y. Krishnan, Elizabeth J. B. Manning and Michael T. Collins^a

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison (Madison, Wisconsin, U.S.A.)

 

Mycobacterium avium subsp. paratuberculosis (MAP) infects patients with inflammatory bowel diseases, in particular Crohn’s disease. Attempts to treat MAP infections with anti-tuberculosis (TB) drugs generally have not resulted in clinical improvement of patients because MAP is resistant to most first-line TB drugs. Due to a lack of antimicrobial susceptibility data with human-origin MAP strains and contemporary testing methods, treatment of MAP infections with other antimicrobials has had to have been done empirically. This study established minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of 10 drugs against 10 MAP strains using the MGIT ParaTB medium™ and MGIT 960 instrument. Depending on the MAP strain, some antimicrobials had synergistic anti-MAP activity with 6-mercaptopurine (6-MP), the active metabolite of azathioprine (AZA). Of 13 novel compounds developed by Sequella, three showed significant anti-MAP activity with MIC values at or lower than those of conventional antimicrobials and MBCs ranging from 1x MIC to 4x MIC. No significant synergistic anti-MAP activity was seen with combinations of two and three antimicrobials. The next phase of drug testing will use the most potent antimicrobials using MAP-infected macrophages.

  

^aPrincipal Investigator