Speaker
Description
Patients with cystic fibrosis (CF) face chronic antibiotic-resistant bacterial infections in their airways, lungs, other mucosal surfaces, and in some cases, bloodstream. Over the patients’ lifetime, these infections become exceedingly difficult to treat. Despite the profound benefits of corrector and modulator drugs that restore some function to the CFTR on quality of life and lifespan, ~10% patients have mutant channels that are not responsive to these drugs. Bacteriophage therapy (PT) in conjunction with antibiotics holds promise for these patients, despite PT lacking clear parameters such as phage doses, delivery, length of treatment, or interactions with antibiotics. Additionally, there are few if any clear-cut criteria for measuring success. We have safely treated with antibiotics and phages several CF patients with multi-drug resistant Achromobacter xylosoxidans infections; one of these patients was treated twice, ~2 years apart. Metagenomic analyses of sputum and blood samples showed that Achromobacter sequences decreased as much as 80% and remained reduced for months. During each round of therapy, some of the isolates became sensitive to antibiotics. No neutralizing antibodies were detected after the first round of therapy (the results from the second round are still being analyzed). Microbiological, genomic, and metagenomic data of Achromobacter strains isolated before, during, and after PT showed changes in both phage and antibiotic sensitivity. Some of the mutations correspond with those conferring phage resistance in vitro. These highlight the dynamics between bacterial fitness and the three-way interactions between the phages, the target pathogen, and antibiotics within human lungs.
