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Since the advent of the use of penicillin to treat infections we have seen a steady rise in the number of pathogens resistant to one or more antibiotics. The current resistance climate has researchers and clinicians alike searching for alternative approaches to treating bacterial infections. The current approach of using broad-spectrum antibiotics decimates a patient’s resident microflora and subjects all of the bacteria in the body to selective pressures. As we can see by the ever-increasing levels of resistance this approach is clearly not working. We propose to treat infections using the strategy that bacteria have employed for millions of years to eliminate their competitors – bacteriocins. These polypeptide antimicrobials, naturally produced by bacteria, are narrow-spectrum (they target very specific organisms). We propose to use this characteristic to our advantage by targeting only the pathogen causing an infection, which ultimately leaves the body’s natural flora intact and reduces levels of selection pressure.
One infection that we are currently targeting is catheter-associated urinary tract infections (CAUTI), which are the most common nosocomial infection in the US with 1 million cases per year. There are approximately 3,000 deaths per year associated with UTIs and the cost for treating CAUTI are astronomical, with total CAUTI intervention costs reaching about $500 million per year in the US. Additionally, treatment for catheter-associated bacteremia costs on average $2,900 per episode. Furthermore, CAUTI is increasingly being seen as a preventable illness that is caused by poor practices in hospitals, therefore, many of the costs associated with CAUTI are no longer being reimbursed by Medicare. This change in policy will leave patients and/or hospitals to bear the financial burden of this infection. To date, no fully effective method to prevent CAUTI exists.
We have shown that bacteriocins are as effective as traditional antibiotics at inhibiting the growth of uropathogenic E. coli. They are also able to kill their targets instantaneously and maintain a sterile environment over the course of 72 hours. We have also shown that the use of combinations of bacteriocins results in a reduction in the emergence of resistance to these antimicrobials. Bacteriocins have so much potential as a new therapeutic for CAUTI because there are bacteriocins that are able to target the most common species implicated in CAUTI.