A New Class of Anti-Clostridioides difficile Antibacterial
Tech ID: 20-062
Inventors: Dr. Shahriar Mobashery, Dr. Mayland Chang
Date added: June 29, 2020
A new class of antibiotic that selectively and potently targets antibiotic-resistant Gram-positive spore-forming C. difficile infections in the large intestine.
Clostridioides difficile (C. difficile or C. diff) is an antibiotic-resistant Gram-positive, anaerobic, spore-forming bacterium. Its production of dormant and antibiotic-impervious spores results in chronic disruption of normal gut flora, and debilitating diarrhea and intestinal infection. C. diff infection (CDI) is considered an urgent health problem as it afflicts approximately 224,000 individuals and kills about 13,000 annually in the US alone. Major challenges for both intravenous and oral chemotherapy of bacterial infections such as CDI are disruption of normal gut flora, the development of resistance, and failure to reduce infection recurrence. The disruption of the normal gut flora due to use of broad-spectrum antibiotics is especially problematic for CDI, because it facilitates the colonization and proliferation of C. diff in the large intestine. Currently, treatments for CDI include metronidazole (MTZ) as the first line for non-severe CDI and vancomycin (VAN) for severe recurrent infections. However, MTZ is absorbed with gut concentrations approaching minimal inhibitory concentrations and it also kills beneficial gut bacteria. Fidaxomicin (FDX) is a narrow-spectrum bactericidal antibiotic effective against C. diff, however its use is limited due to its high cost and decreased efficacy against the highly virulent BI/NAP1/027 strain.
Researchers at the University of Notre Dame have recently discovered a new class of antibiotics that is selective against C. diff cell wall biosynthesis. The compound has potent activity against C. diff at the logarithmic (vegetative) phase of growth without disrupting normal gut flora.
• More potent than vancomycin.
• More selective - disrupts C. difficile cell-wall biosynthesis without killing normal gut flora.
• CDI affects 224,000 Americans and kills 13,000 annually.
Technology Readiness Status
TRL4 - Lab Validation