Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations

Abstract

Lower respiratory tract infections lead to significant morbidity and mortality. They are increasingly caused by multidrug-resistant pathogens, notably in individuals with cystic fibrosis, hospital-acquired pneumonia and lung transplantation. The use of bacteriophages (phages) to treat bacterial infections is gaining growing attention, with numerous published cases of compassionate treatment over the last few years. Although the use of phages appears safe, the lack of standardisation, the significant heterogeneity of published studies and the paucity of robust efficacy data, alongside regulatory hurdles arising from the existing pharmaceutical legislation, are just some of the challenges phage therapy has to overcome. In this review, we discuss the lessons learned from recent clinical experiences of phage therapy for the treatment of pulmonary infections. We review the key aspects, opportunities and challenges of phage therapy regarding formulations and administration routes, interactions with antibiotics and the immune system, and phage resistance. Building upon the current knowledge base, future pre-clinical studies using emerging technologies and carefully designed clinical trials are expected to enhance our understanding and explore the therapeutic potential of phage therapy.

Bacteriophage Therapy of Multidrug-resistant Achromobacter in an 11-Year-old Boy With Cystic Fibrosis Assessed by Metagenome Analysis

“…Phage therapy has been used in the treatment of multidrug-resistant pathogens in adults at many sites of infection, including lung infection in persons with CF. 4,6,[13][14][15] Intravenous administration has been safe in adults and was well tolerated in our patient, with no phage-attributable adverse events noted. Our patient improved clinically as assessed by decreasing cough and improved exercise tolerance during his hospital treatment course with phages, antibiotics and aggressive pulmonary toilet, with sustained improvement beyond the 1-month follow-up visit.…”

“…Phage therapy has been used in the treatment of multidrug-resistant pathogens in adults at many sites of infection, including lung infection in persons with CF. 4,6,13–15…”

Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications

“…Unlike the major therapeutic hurdles of antibiotics and other chemotherapies caused by high degrees of bacteria resistance in clinic, phage therapy provides a new therapeutic approach for precisely editing the intestinal microbiota, completely resolving bacteria resistance and treating liver diseases. Although great advances have presented in various bacterial infection ( Mitropoulou et al., 2022 ; Van Nieuwenhuyse et al., 2022 ), due to the diversity and complexity of gut microbiome, more clinical trials with larger cohorts are required to validate the relevance of the findings in NAFLD patients.…”

Phage-Antibiotic Combination: An Effective Method for Eradication ofStaphylococcus aureus

“…Most clinical reports on phage treatment have shown promising therapeutic outcomes [6]. Additionally, clinical studies have demonstrated encouraging results in treating osteomyelitis [7], bone and joint infections [8] [9], and pulmonary infections [6]. Most clinical studies have reported that the combination of phages and antibiotics is more effective than phage treatment alone [10,11].…”

“…Phage therapy has recently become a more pronounced treatment option in many developed countries [5]. Most clinical reports on phage treatment have shown promising therapeutic outcomes [6]. Additionally, clinical studies have demonstrated encouraging results in treating osteomyelitis [7], bone and joint infections [8] [9], and pulmonary infections [6].…”