Grant: Project Grant - PA: Pandemic Preparedness and Health Emergencies Research

Fix recurrent Bladder infections which affect 1 in 4 of all women and the whole health system benefits economically and with less antibiotic resistance. By 2050, more people are anticipated to die from infections that fail traditional antibiotics than will die from cancer and we need immediate action. A traditional antibiotic costs 2 billion dollars and takes 10 years to develop and then only one DNA change can make the antibiotic ineffective. For over 100 years a non-traditional antibiotic, a good virus, has been used to destroy infection-causing bacteria. This type of virus does not attack humans and is called a bacteriophage (bacteria eater) or phage for short. Like all viruses, they reprogram their target to make more of itself at the target. Phage therapy can be found rapidly for the patient's specific UTI-causing bacteria and provides personalized medicine. We propose a randomized controlled trial targeting the E. coli germ which causes 3 out of 4 of all urinary tract infection organisms. First, we find patients who have failed routine therapy and even specialized intravenous therapy with a strong antibiotic called ertapenem. Second, we send the E. coli bacteria to be tested in a laboratory to find the single or group of phages that can shut down the E. coli in a test tube. Next, when the patient is well and without active infection, purified phages or mock preparations are placed in the bladder once, provided by mouth, and given topically over the vagina. A brief course of ertapenem is given to all patients to improve the phage when given. We then monitor microbiology interactions and the patient to see if they have an infection with the same bacteria within 1 to 6 months. We anticipate that the success with phage will be up to 50% effective vs 10% effective with no phage provided at the one-month mark. We calculate that 50 women are required for recruitment and those that initially receive a placebo will receive phage if they still require care.