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The Problem

The World Health Organization ranks bacterial resistance to antibiotics as one of the top three health care concerns worldwide, with staph bacterial infections being one of the largest contributors to this growing problem.

Antibiotics commonly used to treat staph infections (e.g., penicillin, methicillin, vancomycin, Zyvox) are subject to ever increasing resistance.

According to the CDC, of the estimated annual 2 million hospital-acquired infections in the US, approximately half are due to staph bacteria, including both methicillin-resistant as well as methicillin-sensitive S. aureus and S. epidermidis.

Biofilm Physiology

Until a little over one decade ago, bacteria were thought to act only as independent organisms, in a planktonic state. A bioflim is an aggregate of microbes with a distinct architecture. It is a “microscopic city” in which microbial cells bring nutrients, oxygen and other necessities through fluid filled channels to support life within the biofilm community. Bacteria growing within the biofilm are protected from antibiotic exposure and are up to 1,000 times more resistant than bacteria not growing inside a biofilm [1] [2]. A growing body of peer reviewed publications supports the approach of attacking biofilm as an effective method to combat staph infections.

It is now well know that staph must have a sufficient population (quorum) to allow them to form biofilms, enabling much improved survival in the host. Molecules involved in quorum sensing (QS) by Staphylococci like S. aureus include RNAIII activating protein (RAP), target of RAP (TRAP) and proteins encoded by the accessory gene regulator locus (agr), which ultimately initiate the expression of a myriad of virulence factors such as proteases, hemolysins and various other toxins [3] [4].

The Solution

StaphOff developed CEN-101 (also known as RIP or RNAIII Inhibiting Peptide), the first treatment for staph whose mechanism of action IS NOT to kill the bacteria. Rather, it eliminates the ability of these bacteria to form biofilms, to produce toxins and to survive. The molecule is a heptapeptide that can be delivered by a variety of dosing methods: (1) topical, (2) locally injectable, (3) intravenous administration, and (4) in solution as a medical device coating or in sterile locks.

A large body of compelling evidence exists demonstrating that CEN-101 is effective in preventing and curing staph infections. In vitro data have been published in eight peer reviewed articles. Twenty peer reviewed animal studies have been published for rats, mice, cows, and rabbits, all demonstrating that CEN-101 works effectively in a variety of applications (wound infections, graft associated infections, cellulitis, arthritis, sepsis, osteomyelitis and mastitis) with no observable side effects. Three articles about compassionate use in humans have also been published. All are part of a 323 patient compassionate care study of topical CEN-101, with a overall 91% improvement in outcome in advanced stage wound care patients (reduced number of amputations and reduced number of sepsis-related deaths)[5][6].


  1. James GA, Swogger E, Wolcott R, Pulcini Ed, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):37-44. Epub 2007 Dec 13. PMID:18086294 doi:10.1111/j.1524-475X.2007.00321.x
  2. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999 May 21;284(5418):1318-22. PMID:10334980
  3. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998 Aug 20;339(8):520-32. PMID:9709046 doi:10.1056/NEJM199808203390806
  4. March JC, Bentley WE. Quorum sensing and bacterial cross-talk in biotechnology. Curr Opin Biotechnol. 2004 Oct;15(5):495-502. PMID:15464383 doi:10.1016/j.copbio.2004.08.013
  5. Wolcott, R., Lopez-Leban, F., Kiran, M. D. & Balaban, N. (2011). Wound Healing by an Anti-Staphylococcal Biofilm Approach, in Biofilm Highlights (Flemming, H.-C., Wingender, J. & Szewzyk, U., eds.), pp. 141-161, Springer, Heidelberg
  6. Lopez-Leban F, Kiran MD, Wolcott R, Balaban N. Molecular mechanisms of RIP, an effective inhibitor of chronic infections. Int J Artif Organs. 2010 Sep;33(9):582-9. PMID:20963725

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Joel L. Sussman

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