Tailor 12

The emergence of multi-drug resistance (MDR) to chemical antibiotics is threatening to undermine an entire sector of modern medicine. Dire predictions call for 10 million deaths in the next three decades at a cost of trillions to governments and healthcare. The problem is compounded by the inherent adaptability and evolution of bacteria in the face of intense selective pressures. As such, bacteriophages, viruses that infect bacteria and themselves are diverse and evolvable, have been proposed as a possible solution for this crisis. Here, we report progress following the formation of TAILOR (Tailored Antimicrobials and Innovative Phage Research), whose driving mission was to create a library and pipeline of tailored phage cocktails for an individual strains from a patient for use in personalized compassionate care cases. Here we report an extensive amount of information for the first 12 cases, referred to here as the Tailor 12 (T12), including the discovery, pipeline and process of phage selection and purification, individual phage characteristics, infection conditions and environment, and patient outcomes. These personalized phage cocktails were extensively characterized lytic killing assays, stability testing, endotoxin and other toxin screening, sterility testing, sequence analysis and antibiotic synergy assays, prior to treatment for eventual submission and approval by the FDA for expanded access clinical use. We report the use of phages adapted by directed evolution, natural phages from diverse environment sources, phages from several genera, and phages with enhanced properties (such as the prevention of resistance, the destruction of biofilms, or the adherence to human mucosa). Patient infections ranged from urinary tract infections (UTI) to infections from devices or prosthesis (prosthetic joint infection or PJI; left ventricular assist device infection or LVAD), surgical would infections (sternotomy) and bacteremia. The causative organisms of these infections were mostly from the group of nosocomial pathogens commonly referred to as the ESKAPE pathogens: E. cloacae, K. aerogenes, K. pneumonia, S. aureus, P. aeruginosa and E. coli. This report provides a summary of all available data on these cases to enhance the basic and clinical science around a personalized or tailored approach for phage therapy. The generation of a worldwide network of phage centers like TAILOR will fill a critical treatment void for the most complex and challenging patients suffering either from antibiotic failure or difficult to treat infections or both.