Early clinical experience of bacteriophage therapy in 3 lung transplant recipients

Am J Transplant. 2019 Sep;19(9):2631-2639. doi: 10.1111/ajt.15503. Epub 2019 Jul 17.

Abstract

Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.

Keywords: antibiotic drug resistance; antibiotic: antibacterial; clinical research/practice; infection and infectious agents - bacterial; infectious disease; lung disease: infectious; lung transplantation/pulmonology; translational research/science.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / prevention & control*
  • Bacterial Infections / therapy*
  • Burkholderia
  • Drug Resistance, Multiple, Bacterial*
  • Female
  • Humans
  • Lung Diseases / complications
  • Lung Diseases / microbiology
  • Lung Diseases / surgery*
  • Lung Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Phage Therapy / methods*
  • Postoperative Complications
  • Pseudomonas aeruginosa
  • Respiratory Tract Infections / microbiology
  • Transplant Recipients

Substances

  • Anti-Bacterial Agents

Supplementary concepts

  • Burkholderia dolosa