Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans.
Female
Humans
Anti-Bacterial Agents
/ therapeutic use
Burkholderia cepacia complex
Burkholderia Infections
/ drug therapy
Cystic Fibrosis
/ microbiology
DNA
/ therapeutic use
Leukocytosis
/ drug therapy
Lipopolysaccharides
/ therapeutic use
Lung
/ microbiology
Phage Therapy
Transplant Recipients
Fatal Outcome
Adult
Burkholderia
antibiotic resistance
cystic fibrosis
phage therapy
Journal
Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
06
02
2023
received:
23
10
2022
accepted:
09
02
2023
pmc-release:
01
04
2024
medline:
11
4
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
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. 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. 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. This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.
Identifiants
pubmed: 36864824
doi: 10.1111/tid.14041
pmc: PMC10085838
mid: NIHMS1875177
doi:
Substances chimiques
Anti-Bacterial Agents
0
DNA
9007-49-2
Lipopolysaccharides
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14041Subventions
Organisme : Cystic Fibrosis Foundation
ID : BOMBER19R0
Organisme : National Institute of Allergy and Infectious Diseases
ID : K23AI154546
Organisme : Department of Medicine at the University of Pittsburgh School of Medicine
Organisme : NIAID NIH HHS
ID : K23 AI154546
Pays : United States
Organisme : Cystic Fibrosis Foundation
ID : VANTYN21GO
Informations de copyright
© 2023 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.
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