Supercharged vancomycin analogues beat the superbug <em>C. difficile</em> — ASN Events
  1. Schedule
  2. Welcome Reception, Poster Session I & Trade Exhibition
  3. Supercharged vancomycin analogues beat the superbug C. difficile

Supercharged vancomycin analogues beat the superbug C. difficile (#223)

Angie M Jarrad 1 , Zyta M Ziora 1 , Fredrik Lindahl 1 , Tanya A Bradford 1 , Karl A Hansford 1 , Craig A Muldoon 1 , Rajaratnam Premraj 1 , Soumya Ramu 1 , Johnny X Huang 1 , Angela M Kavanagh 1 , Ruby Pelingon 1 , David J Edwards 1 , Mark S Butler 1 , Mark A Blaskovich 1 , Tomislav Karoli 1 , Matt A Cooper 1
  1. University of Queensland, St Lucia, QLD, Australia

Clostridium difficile is a Gram positive, spore forming anaerobic bacteria that is the leading cause of healthcare-associated diarrhoea.1 It imparts a significant burden on the community, estimated to cost the USA more than $496 million annually.2 One of main treatments for C. difficile infection is oral vancomycin, a glycopeptide antibiotic. However, vancomycin treatment fails in ~ 20% of patients resulting in high relapse rates.3,4 In addition, increasing resistance to vancomycin has been observed and new treatments are highly desired.5,6 We have developed vancomycin analogues that contain additional elements designed to improve binding to bacterial membranes, the site of vancomycin’s target. These compounds are 500 fold more active than vancomycin against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant S. aureus and vancomycin resistant enterococci. Vancomycin analogues are presented here that are 30 fold more potent than vancomycin and 15 times more potent than metronidazole against C. difficile in in vitro assays and with improved bactericidal activity compared to vancomycin. A comparison of MIC activity against C. difficile with the superbugs mentioned above is highlighted. 

  1. Khanna, S. & Pardi, D. S. Clostridium difficile Infection: New Insights Into Management. Mayo Clinic Proceedings 87, 1106–1117 (2012).
  2. McGlone, S. M. et al. The economic burden of Clostridium difficile. Clin Microbiol Infect 18, 282–289 (2012).
  3. Venugopal, A. A. & Johnson, S. Current state of Clostridium difficile treatment options. Clinical Infectious Diseases 55 Suppl 2, S71–6 (2012).
  4. Pepin, J. et al. Increasing Risk of Relapse after Treatment of Clostridium difficile Colitis in Quebec, Canada. Clinical Infectious Diseases 40, 1591–1597 (2005).
  5. Freeman, J. et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 23, 529–549 (2010).
  6. Snydman, D. R. et al. Activity of a novel cyclic lipopeptide, CB-183,315, against resistant Clostridium difficile and other Gram-positive aerobic and anaerobic intestinal pathogens. Antimicrobial Agents and Chemotherapy 56, 3448–3452 (2012).