Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug‐resistant Burkholderia multivorans

Abstract

Background There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic‐resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died. Methods Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis. Results Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O‐antigen profiles of an early versus a late isolate. Conclusions This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia

“…These characteristics have allowed enterococci to become successful nosocomial pathogens, especially in immunocompromised populations ( 2 ). Bacteriophages (phages) offer a potential adjunctive tool to manage infections with multi-drug-resistant bacteria ( 3 , 4 ). However, few reports have demonstrated in vivo efficacy of phage therapy for E. faecium infections in humans ( 5 , 6 ).…”

Investigational non‐antibiotic therapeutics for infections in hematopoietic cell transplant recipients and patients with hematologic malignancies receiving cellular therapies

“…Bacteriophages, or viruses that infect bacteria, have been used to treat refractory bacterial infections in immunocompromised patients, specifically solid organ transplant recipients. [30][31][32][33] However, to our knowledge, there are no published reports of bacteriophages used to treat patients undergoing HCT or cellular therapies. Nonetheless, we have elected to review bacteriophage therapy, as this remains an area of unexplored potential for hematologic malignancy patients with refractory bacterial infections.…”

“…Bacteriophages, or viruses that infect bacteria, have been used to treat refractory bacterial infections in immunocompromised patients, specifically solid organ transplant recipients 30–33 . However, to our knowledge, there are no published reports of bacteriophages used to treat patients undergoing HCT or cellular therapies.…”

Harnessing the diversity ofBurkholderiaspp. prophages for therapeutic potential

“…While phage therapy for Burkholderia spp. infections would be advantageous, to date only three compassionate use cases of Burkholderia -targeting phages have been reported [17–19]. However, studies investigating the use of phages to treat Burkholderia spp.…”