Safety and Efficacy of Bacteriophage Therapy in Lung Transplant Candidates and Recipients

Abstract

Purpose Bacteriophage therapy (BT) employs lytic bacteriophages to treat pathogenic bacteria. Although BT is an emerging strategy against multidrug-resistant (MDR) infections, experience in solid organ transplant is limited. We describe BT in four lung transplant candidates and recipients with life-threatening MDR infections, including Pseudomonas aeruginosa (PsA) (n=3) and Burkholderia dolosa (n=1) Methods For each patient, lytic bacteriophages were selected against their bacterial isolates (Table 1). Intravenous (IV) bacteriophage was administered for variable durations under individual emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical and laboratory parameters and efficacy was based on clinical resolution of infection. All patients received concurrent antibiotics. Results One lung transplant candidate and three recipients received BT. The transplant candidate had developed acute kidney injury (AKI) on IV colistin for MDR PsA prompting adjunctive BT administration. Following BT, colistin was discontinued, oxygen requirements improved, AKI resolved, and she went on to lung transplant. Two ventilator dependent recipients with refractory MDR PsA pneumonia despite antibiotic therapy and multiple pulmonary procedures to mitigate airway complications also received BT therapy. Both patients were weaned from mechanical ventilation prior to hospital discharge. A fourth patient had recurrent B. dolosa infection following transplant despite IV antibiotic therapy. Following BT initiation consolidative opacities improved and ventilator weaning was begun. There were no treatment-related adverse events reported in the four cases. Conclusion BT was well-tolerated and was associated with clinical efficacy when used as an adjunct to antibiotics in patients who were not responsive to antibiotics alone. Bacteriophage therapy may be a viable adjunct to antibiotics in the era of increasing antimicrobial resistance.