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

dc.contributor.authorHaidar, Ghady
dc.contributor.authorChan, Benjamin K.
dc.contributor.authorCho, Shu-Ting
dc.contributor.authorHughes Kramer, Kailey
dc.contributor.authorNordstrom, Hayley R.
dc.contributor.authorWallace, Nathan R.
dc.contributor.authorStellfox, Madison E.
dc.contributor.authorHolland, Mische
dc.contributor.authorKline, Ellen G.
dc.contributor.authorKozar, Jennifer M.
dc.contributor.authorKilaru, Silpa D.
dc.contributor.authorPilewski, Joseph M.
dc.contributor.authorLiPuma, John J.
dc.contributor.authorCooper, Vaughn S.
dc.contributor.authorShields, Ryan K.
dc.contributor.authorVan Tyne, Daria
dc.date.accessioned2023-05-01T19:11:25Z
dc.date.available2024-05-01 15:11:23en
dc.date.available2023-05-01T19:11:25Z
dc.date.issued2023-04
dc.identifier.citationHaidar, Ghady; Chan, Benjamin K.; Cho, Shu-Ting ; Hughes Kramer, Kailey; Nordstrom, Hayley R.; Wallace, Nathan R.; Stellfox, Madison E.; Holland, Mische; Kline, Ellen G.; Kozar, Jennifer M.; Kilaru, Silpa D.; Pilewski, Joseph M.; LiPuma, John J.; Cooper, Vaughn S.; Shields, Ryan K.; Van Tyne, Daria (2023). "Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug- resistant Burkholderia multivorans." Transplant Infectious Disease 25(2): n/a-n/a.
dc.identifier.issn1398-2273
dc.identifier.issn1399-3062
dc.identifier.urihttps://hdl.handle.net/2027.42/176290
dc.description.abstractBackgroundThere 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.MethodsPhages 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.ResultsPhage 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.ConclusionsThis case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.A critically ill lung transplant recipient with CF and B. multivorans sepsis was treated with phage therapy for 7 days before they died. We investigated phage and antibiotic susceptibility of serial B. multivorans isolates collected from the patient as well as phage pharmacokinetics and immune responses.
dc.publisherRandom House
dc.publisherWiley Periodicals, Inc.
dc.subject.otherantibiotic resistance
dc.subject.otherphage therapy
dc.subject.othercystic fibrosis
dc.subject.otherBurkholderia
dc.titlePhage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMedicine (General)
dc.subject.hlbsecondlevelMicrobiology and Immunology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176290/1/tid14041_am.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176290/2/tid14041-sup-0002-figureS1-S2.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176290/3/tid14041.pdf
dc.identifier.doi10.1111/tid.14041
dc.identifier.sourceTransplant Infectious Disease
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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