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Impact of Burkholderia Infection on Lung Transplantation in Cystic Fibrosis
Open accessAbstract
Rationale: Lung transplantation offers the only survival option for patients with cystic fibrosis (CF) with end-stage pulmonary disease. Infection with Burkholderia species is typically considered a contraindication to transplantation in CF. However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined. Objectives: To quantify the risks of infection with Burkholderia species on survival before and after lung transplantation in patients with CF. Methods: Multivariate Cox survival models assessed hazard ratios of infection with Burkholderia species in 1,026 lung transplant candidates and 528 lung transplant recipients. Lung allocation scores, incorporating Burkholderia infection status, were calculated for transplant candidates. Measurements and Main Results: Transplant candidates infected with different Burkholderia species did not have statistically different mortality rates. Among transplant recipients infected with B. cenocepacia, only those infected with nonepidemic strains had significantly greater post-transplant mortality compared with uninfected patients (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04–6.12; P = 0.04). Hazards were similar between uninfected transplant recipients and those infected with B. multivorans (HR, 0.66; 95% CI, 0.27–1.56; P = 0.34). Transplant recipients infected with B. gladioli had significantly greater post-transplant mortality than uninfected patients (HR, 2.23; 95% CI, 1.05–4.74; P = 0.04). Once hazards for species/strain were included, lung allocation scores of B. multivorans–infected transplant candidates were comparable to uninfected candidate scores, whereas those of candidates infected with nonepidemic B. cenocepacia or B. gladioli were lower. Conclusions: Post-transplant mortality among patients with CF infected with Burkholderia varies by infecting species. This variability should be taken into account in evaluating lung transplantation candidates.
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“particularly B. cenocepacia has been associated with post-transplant infections and increased mortality especially within the first 6–12 months.(72, 73)”
From Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. (2021) · cites this paper as [73]
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Hirche, T. O., Knoop, C., Hebestreit, H. U., Shimmin, D., Solé, A., Elborn, J. S., Ellemunter, H., Aurora, P., Hogardt, M., Wagner, T. O. F., et al. (2014) · Pulmonary Medicine · doi:10.1155/2014/621342 · Cited by 78
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“We were unable to analyze its effect on survival, owing to a small number of patients (n=4) with documented infection or colonization (28, 29).”
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Morrell, M. R., Kiel, S., & Pilewski, J. M. (2019) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0039-3399554 · Cited by 32
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“[3] compared predicted survival of CF BCC infected patients on a LTx waiting list (n=171) to predicted survival following LTx of CF BCC infected patients (n=88), using a multivariate Cox survival model.”
BackgroundMethodAssessment of infection risks prior to lung transplantation
Luong, M., Morrissey, O., & Husain, S. (2010) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e32833f9f93 · Cited by 29
Clinical andin vitroevidence for the antimicrobial therapy inBurkholderia cepaciacomplex infections
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“However, infection with the nonepidemic strain of B cenocepacia resulted in a significantly increased risk of posttransplant mortality compared with uninfected control subjects.(13) It has also been shown that B cenocepacia strain E12, which is more common in Canada and the United Kingdom, results in increased mortali…”
BackgroundUpdate in Lung Transplantation 2008
Lama, V. N. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200902-0177up · Cited by 27
Horsley, A. R., & Jones, A. M. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009529.pub2 · Cited by 27
Lung transplantation in cystic fibrosis patients with difficult to treat lung infections
Dupont, L. (2017) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000431 · Cited by 26
Los-Arcos, I., Len, O., Martín-Gómez, M. T., González-López, J. J., Saéz-Giménez, B., Deu, M., Nuvials, X., Ferrer, R., Román, A., & Gavaldà, J. (2019) · Infection · doi:10.1007/s15010-018-1261-y · Cited by 24
Accurate identification of members of the Burkholderia cepacia complex in cystic fibrosis sputum
Martinucci, M., Roscetto, E., Iula, V. D., Votsi, A., Catania, M. R., & Gregorio, E. D. (2015) · Letters in Applied Microbiology · doi:10.1111/lam.12537 · Cited by 25
“Indeed, CF patients infected by B. cenocepacia and B. gladioli have a poor prognosis, and had been debated their eligibility for lung transplant (Murray et al. 2008).”
BackgroundLong term complications following 54 consecutive lung transplants
Tabarelli, W., Bonatti, H., Tabarelli, D., Eller, M., Müller, L. C., Ruttmann, E., Lass‐Flörl, C., Larcher, C., & Geltner, C. (2016) · Journal of Thoracic Disease · doi:10.21037/jtd.2016.05.03 · Cited by 25
Quon, B. S., Reid, J. D., Wong, P. H. P., Wilcox, P., Javer, A. R., Wilson, J. M., & Levy, R. D. (2011) · Canadian Respiratory Journal · doi:10.1155/2011/304179 · Cited by 25
Candidate Selection, Timing of Listing, and Choice of Procedure for Lung Transplantation
Kreider, M., Hadjiliadis, D., & Kotloff, R. M. (2011) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2011.02.001 · Cited by 24
Guidelines for the selection of lung-transplant candidates
Shah, P. D., & Orens, J. B. (2012) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e328357d898 · Cited by 23
“In two separate studies, recipients with non-Cenocepacia BCC had comparable survival to uninfected recipients, suggesting that these patients could be transplanted safely [24,25].”
BackgroundResultRecent Advances in Cystic Fibrosis
Lobo, J., Rojas-Balcazar, J., & Noone, P. G. (2012) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2012.02.006 · Cited by 23
den Driessche, F. V., Vanhoutte, B., Brackman, G., Crabbé, A., Rigole, P., Vercruysse, J., Verstraete, G., Cappoen, D., Vervaet, C., Cos, P., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172723 · Cited by 23
“cenocepacia are associated with lower survival following lung transplantation [4,5].”
BackgroundInfluentialUpdate in Cystic Fibrosis 2008
Ratjen, F. A. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200812-1927up · Cited by 22
Lung Transplantation for Advanced Bronchiectasis
Hayes, D., & Meyer, K. (2010) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0030-1249109 · Cited by 22
Pediatric Lung Transplantation
Huddleston, C. B. (2010) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-010-0105-6 · Cited by 21
Special considerations for the use of lung transplantation in pediatrics
Schmid, F. A., & Benden, C. (2016) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2016.1168298 · Cited by 20
Torre‐Cisneros, J., Ferrer, R., Martos, C. D. L. F., Sarda, J., Calvo, A. J. G., Verardi, S., Karas, A., & Soriano, À. (2025) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-025-05109-5 · Cited by 19
Huse, H. K., Lee, M. J., Wootton, M., Sharp, S. E., Traczewski, M., LiPuma, J. J., & Jorth, P. (2021) · Journal of Clinical Microbiology · doi:10.1128/jcm.01447-21 · Cited by 19
“cenocepacia are associated with better and worse survival post lung transplant, respectively (6, 22).”
BackgroundInfluentialSelf-citationBronchiolitis and bacteraemia caused by Burkholderia gladioli in a non-lung transplantation patient
Imataki, O., Kita, N., Nakayama‐Imaohji, H., Kida, J., Kuwahara, T., & Uemura, M. (2014) · New Microbes and New Infections · doi:10.1002/nmi2.64 · Cited by 19
“gladioli are associated with poor graft survival and unfavourable outcomes [1,2].”
BackgroundUpdate on antibiotics for infection control in cystic fibrosis
Kirkby, S. E., Novak, K. J., & McCoy, K. (2009) · Expert Review of Anti-infective Therapy · doi:10.1586/eri.09.82 · Cited by 19
Wong, K., Dhaliwal, S., Bilawka, J., Srigley, J. A., Champagne, S., Romney, M. G., Tilley, P. A. G., Sadarangani, M., Zlosnik, J. E. A., & Chilvers, M. A. (2020) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001223 · Cited by 17
“gladioli have been reported as having adverse outcomes postlung transplant [6, 37, 38] and may be considered relative or even absolute contraindications to lung transplant in some centres [39–41].”
BackgroundBrizendine, K. D., Baddley, J. W., Pappas, P. G., Leon, K. J., & Rodriguez, J. M. (2012) · Transplant Infectious Disease · doi:10.1111/j.1399-3062.2012.00726.x · Cited by 17
“(19), who performed an interesting retrospective multivariate survival analysis that assessed the hazards of infection with Burkholderia species.”
BackgroundDeath after Lung Transplantation in Cystic Fibrosis Patients Infected with Burkholderia cepacia
Hopkins, P. M.-A., Kidd, T. J., Coulter, C., Feather, I. H., Derrington, P., & Bell, S. C. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.179.3.257 · Cited by 17
Managing Pulmonary Infection in Adults With Cystic Fibrosis
Green, H. D., & Jones, A. M. (2022) · CHEST Journal · doi:10.1016/j.chest.2022.02.007 · Cited by 16
Patel, G., Rana, M. M., & Huprikar, S. S. (2013) · Current Infectious Disease Reports · doi:10.1007/s11908-013-0371-z · Cited by 16
Selection of cystic fibrosis patients for lung transplantation
Aurora, P., Carby, M. R., & Sweet, S. C. (2008) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328313e3d4 · Cited by 16
Lung transplantation for cystic fibrosis: an update
Chaparro, C., & Keshavjee, S. H. (2016) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2016.1261016 · Cited by 15
“cepacia and there are only case reports with variable results [72,84].”
BackgroundCarraro, D. D. S., Carraro, R. M., Campos, S. V., Iuamoto, L. R., Braga, K. A. D. O., de Oliveira, L. C., Sabino, É. C., Rossi, F., & Pêgo‐Fernandes, P. M. (2018) · Clinics · doi:10.6061/clinics/2018/e166 · Cited by 15
“was not associated with an unacceptably high risk of a fatal outcome after LTx, although a relationship with poorer long-term survival was found (20,21).”
BackgroundMiller, R. R., Hird, T. J., Tang, P., & Zlosnik, J. E. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0143472 · Cited by 15
LiPuma, J. J., Currie, B. J., Peacock, S. J., & Vandamme, P. A. R. (2011) · doi:10.1128/9781555816728.ch41 · Cited by 15
Self-citationReed, A. K., Mercier, O. M., Behr, J., Dave, K., Dellgren, G., Kotecha, S., Kukreja, J., Landry, C., Levvey, B. J., Lyster, H. S., et al. (2025) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2025.07.033 · Cited by 15
Marrs, E. C. L., Perry, A., & Perry, J. D. (2021) · Microorganisms · doi:10.3390/microorganisms9122604 · Cited by 13
“Post lung transplantation, Burkholderia cenocepacia is particularly associated with an increased rate of mortality [5,6] and, in many centres, infection with B.”
BackgroundSuccessful lung re-transplant in a patient with cepacia syndrome due to Burkholderia ambifaria
Goodlet, K. J., Nailor, M. D., Omar, A., Huang, J. L., LiPuma, J. J., Walia, R., & Tokman, S. (2019) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.08.011 · Cited by 12
Self-citationInfections in lung transplantation: new insights
Hafkin, J., & Blumberg, E. A. (2009) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32833062f6 · Cited by 12
Cystic fibrosis, primary ciliary dyskinesia and non-cystic fibrosis bronchiectasis: update 2008–11
Flight, W. G., & Jones, A. M. (2011) · Thorax · doi:10.1136/thoraxjnl-2011-200467 · Cited by 12
Metadata
- Authors
- Murray, S., Charbeneau, J., Marshall, B. C., & LiPuma, J. J.
- Affiliations
- University of Michigan (US)
- Cystic Fibrosis Foundation (US)
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-08
- Volume
- 178
- Issue
- 4
- Pages
- 363-371
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2081925747
- Semantic Scholar
- 68cf39ee60f9774eb35ae3f703478d0c836ebf29
- Cited by
- 177
- References
- 40
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 13 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 9 · 2015: 13 · 2014: 14 · 2013: 8 · 2012: 12
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- Cystic Fibrosis Foundation
- Health Resources and Services Administration
- Topics
- Health Sciences › Medicine › Epidemiology › Burkholderia infections and melioidosis
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Microbiology (medical) › Infections and bacterial resistance
- Keywords
- cystic fibrosis, lung transplantation, Burkholderia cenocepacia, Burkholderia multivorans, Burkholderia gladioli, post-transplant mortality, lung allocation score, transplant candidates
- MeSH terms
- Contraindications, Adult, Cystic Fibrosis, Female, Humans, Male, Postoperative Complications, Prognosis, Risk, United States, Cohort Studies, Survival Rate, Multivariate Analysis, Case-Control Studies, Lung Transplantation, Treatment Outcome, Pneumonia, Bacterial, Disease-Free Survival, Burkholderia Infections
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