Phage Therapy in Lung Transplantation

An impactful review article on phage therapy by Saima Aslam, IPATH

After the seminal case of intravenous phage therapy in the United States in 2016, the past 7 years have seen an explosion of interest in using lytic phage for the treatment of multidrug-resistant (MDR) and biofilm-based infections in Western medicine [1–3]. Phage has historically been available as an over-the-counter treatment for a variety of clinical indications in Eastern Europe and Russia though not much publicized or rigorously studied before and generally used in oral or inhaled formulations. However, the ongoing MDR pandemic has forced us to think outside the confines of conventional antibiotic therapy for antibiotic recalcitrant infections [4].

Lung transplantation for end-stage lung disease is increasing globally, with almost 34 000 lung transplantation between 2010 and 2018 [5]. Lung transplant candidates and recipients are a unique population characterized by MDR pathogen colonization and infection, recurrent pulmonary infection, high biomass of the respiratory microbiome (especially in the setting of bronchiectactic lung disease), polymicrobial infections, reduced mucociliary clearance, and immunosuppression [5, 6]. Immunosuppression can be in the pretransplant period (eg, in the use of recurrent courses of steroids for chronic obstructive pulmonary disease or antiproliferative and cytotoxic agents in various autoimmune lung diseases) as well as induction immunosuppression at the time of transplant surgery followed by triple immunosuppression in the transplant recipient with steroids, calcineurin inhibitors, and cell cycle inhibitors; many patients develop acquired hypogammaglobulinemia as well requiring monthly intravenous immunoglobulin infusions [7]. Globally, about 15%–20% of lung transplant recipients (LTRs) have underlying cystic fibrosis (CF), a unique subset marked by younger age, higher rates of MDR pathogen colonization than in other LTRs, higher rate of antibiotic allergies, and increased risk for posttransplant infectious complications [5, 6, 8].

More recently during the coronavirus disease 2019 (COVID-19) pandemic, there has been a remarkable increase in lung transplantation for COVID-19–related acute respiratory distress syndrome—8.7% of all lung transplantations in the United States in 2020–2022 were for COVID-19–related acute respiratory distress syndrome [9]. Many of these patients required prolonged periods of mechanical ventilation and extracorporeal membrane oxygenation in the pretransplantation period, and they are at increased risk of nosocomial infections, especially those due to MDR gram-negative bacteria (g, Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii) and Aspergillus species [9, 10]. Infectious complications are the leading cause of death in LTRs, accounting for almost 30% of deaths in the first posttransplant year and about 20% thereafter [5]. Main pathogens of interest in the lung transplant setting include P. aeruginosa, methicillin-resistant Staphylococcus aureus, Burkholderia cepacia complex species, Mycobacterium abscessus, Stenotrophomonas maltophilia, and Achromobacter xyloxidans. These organisms tend to be MDR with very limited therapeutic options.