Pseudomonas aeruginosa and Staphylococcus aureus are bacterial pathogens frequently associated with pulmonary complications and disease progression in cystic fibrosis (CF). However, these bacteria increasingly show resistance to antibiotics, necessitating novel management strategies. One possibility is bacteriophage (phages; bacteria‐specific viruses) therapy, where lytic phages are administered to kill target bacterial pathogens. Recent publications of case reports of phage therapy to treat antibiotic‐resistant lung infections in CF have garnered significant attention. These cases exemplify the renewed interest in phage therapy, an older concept that is being newly updated to include rigorous collection and analysis of patient data to assess clinical benefit, which will inform the development of clinical trials. As outcomes of these trials become public, the results will valuable gauge the potential usefulness of phage therapy to address the rise in antibiotic‐resistant bacterial infections. In addition, we highlight the further need for basic research to accurately predict the different responses of target bacterial pathogens when phages are administered alone, sequentially, or as mixtures (cocktails), and whether within‐cocktail interactions among phages hold consequences for the efficacy of phage therapy in patient treatment.
Bacteriophage therapy, which uses lytic viruses as antimicrobials, has received renewed interest to address the emerging antimicrobial resistance (AMR) crisis. Cystic fibrosis (CF), a disease complicated by recurrent P. aeruginosa pulmonary infections that cause lung function decline, is an example where AMR is already a clinical problem. While bacteria evolve bacteriophage resistance, we developed a strategy to select bacteriophages that target bacterial cell surface receptors that contribute to antibiotic resistance or virulence. Thus, in addition to killing bacteria, these phages steer surviving, evolved bacteria to antibiotic re-sensitivity or attenuated virulence. Here, we present outcomes from nine CF adults treated with nebulized bacteriophage therapy for AMR P. aeruginosa using this personalized approach. Results showed that phage therapy: 1) reduced sputum P. aeruginosa, 2) showed evidence for predicted trade-offs in most subjects, and 3) improved lung function, which may reflect the combined effects of decreased bacterial sputum density and phage-driven evolved trade-offs.
Pseudomonas aeruginosa and Staphylococcus aureus are bacterial pathogens frequently associated with pulmonary complications and disease progression in cystic fibrosis (CF) patients. However, these bacteria increasingly show multiple resistance to antibiotics, necessitating novel management strategies. One possibility is phage therapy, where lytic bacteriophages (phages; bacteria-specific viruses) are administered to kill target bacterial pathogens. Recent publication of case reports of phage-therapy treatment of antibiotic-resistant lung infections in CF has garnered significant attention. These cases exemplify the renewed interest in phage therapy, as an older concept that is newly updated to include rigorous collection and analysis of patient data to assess clinical benefit, while informing the development of clinical trials. As outcomes of these trials become public, the results will valuably gauge the potential usefulness of phage therapy to address the rise in antibiotic-resistant bacterial infections. In addition, we highlight the further need for basic research on accurately predicting the different responses of target bacterial pathogens when phages are administered alone, sequentially or as mixtures (cocktails), and whether within-cocktail interactions among phages hold consequences for the efficacy of phage therapy in patient treatment.
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