Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1–91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

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Lung transplantation in two cystic fibrosis patients infected with previously pandrug-resistant Burkholderia cepacia complex treated with ceftazidime–avibactam

Infection ◽

10.1007/s15010-018-1261-y ◽

2018 ◽

Vol 47 (2) ◽

pp. 289-292 ◽

Cited By ~ 6

Author(s):

Ibai Los-Arcos ◽

Oscar Len ◽

María Teresa Martín-Gómez ◽

Juan José González-López ◽

Berta Saéz-Giménez ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Transplantation ◽

Burkholderia Cepacia ◽

Burkholderia Cepacia Complex

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Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02068-15 ◽

2015 ◽

Vol 60 (1) ◽

pp. 348-355 ◽

Cited By ~ 7

Author(s):

Sarah Kennedy ◽

Trevor Beaudoin ◽

Yvonne C. W. Yau ◽

Emma Caraher ◽

James E. A. Zlosnik ◽

...

Keyword(s):

Cystic Fibrosis ◽

Burkholderia Cepacia ◽

Burkholderia Cenocepacia ◽

Burkholderia Cepacia Complex ◽

Suppressive Therapy ◽

High Dose ◽

Lung Function Decline ◽

Complex Species ◽

Content Type ◽

Biofilm Thickness

ABSTRACTPulmonary infection withBurkholderia cepaciacomplex in cystic fibrosis (CF) patients is associated with more-rapid lung function decline and earlier death than in CF patients without this infection. In this study, we used confocal microscopy to visualize the effects of various concentrations of tobramycin, achievable with systemic and aerosolized drug administration, on matureB. cepaciacomplex biofilms, both in the presence and absence of CF sputum. After 24 h of growth, biofilm thickness was significantly reduced by exposure to 2,000 μg/ml of tobramycin forBurkholderia cepacia,Burkholderia multivorans, andBurkholderia vietnamiensis; 200 μg/ml of tobramycin was sufficient to reduce the thickness ofBurkholderia dolosabiofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for allBurkholderiaspecies. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml forB. cepaciaandB. dolosa(24 h) and ≥100 μg/ml forBurkholderia cenocepaciaandB. dolosa(48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 μg/ml were still able to significantly reduce biofilm thickness of allB. cepaciacomplex species with the exception ofB. vietnamiensis. In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only forB. multivoranscompared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness ofB. cepaciacomplex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF.

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The impact of the high emergency lung transplantation program in cystic fibrosis in France: insight from a comparison with Canada

European Respiratory Journal ◽

10.1183/13993003.00014-2021 ◽

2021 ◽

pp. 2100014

Author(s):

Adèle Coriati ◽

Jenna Sykes ◽

Lydie Lemonnier ◽

Xiayi Ma ◽

Sanja Stanojevic ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Transplantation ◽

Population Based ◽

Transplant Survival ◽

Post Transplant ◽

Kaplan Meier ◽

Before And After ◽

Cumulative Incidence Curve ◽

The Impact ◽

To Receive

IntroductionFrance implemented a high emergency lung transplantation (HELT) program nationally in 2007. A similar program does not exist in Canada. The objectives of our study were to compare health outcomes within France as well as between Canada and France before and after the HELT program in a population with Cystic Fibrosis (CF).MethodsThis population-based cohort study utilised data from the French and Canadian CF registries. A cumulative incidence curve assessed time to transplant with death without transplant as competing risks. The Kaplan-Meier method was used to estimate post-transplant survival.ResultsBetween 2002 and 2016, there were 1075 (13.0%) people with CF in France and 555 (10.2%) people with CF in Canada who underwent lung transplantation. The proportion of lung transplant increased in France after the HELT program was initiated (4.5% versus 10.1%) whereas deaths pre-transplant decreased from 85.3% in the pre-HELT to 57.1% in the post-HELT period. Between 2008–2016, people in France were significantly more likely to receive a transplant (Hazard Ratio (HR) 1.56, 95% CI 1.37–1.77, p<0.001) than die (HR 0.55, 95% CI 0.46–0.66, p<0.001) compared to Canada. Post-transplant survival was similar between the countries and there was no difference in survival when comparing pre- and post-HELT period in France.ConclusionFollowing the implementation of the HELT program, people living with CF in France were more likely to receive a transplant than die. Post-transplant survival in the post-HELT period in France did not change compared to the pre-HELT period, despite potentially sicker patients being transplanted, and is comparable to Canada.

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Six-Year Molecular Analysis of Burkholderia cepacia Complex Isolates among Cystic Fibrosis Patients at a Referral Center for Lung Transplantation

Journal of Clinical Microbiology ◽

10.1128/jcm.40.4.1188-1193.2002 ◽

2002 ◽

Vol 40 (4) ◽

pp. 1188-1193 ◽

Cited By ~ 23

Author(s):

D. G. Heath ◽

K. Hohneker ◽

C. Carriker ◽

K. Smith ◽

J. Routh ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Transplantation ◽

Molecular Analysis ◽

Burkholderia Cepacia ◽

Burkholderia Cepacia Complex ◽

Referral Center

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Activity of Cysteamine against the Cystic Fibrosis Pathogen Burkholderia cepacia Complex

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01198-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 6200-6206 ◽

Cited By ~ 7

Author(s):

Douglas Fraser-Pitt ◽

Derry Mercer ◽

Emma Lovie ◽

Jennifer Robertson ◽

Deborah O'Neil

Keyword(s):

Cystic Fibrosis ◽

Biofilm Formation ◽

Burkholderia Cepacia ◽

Standard Of Care ◽

Burkholderia Cepacia Complex ◽

Content Type ◽

Folate Pathway ◽

The Impact ◽

Slow Growing

ABSTRACTThere are no wholly successful chemotherapeutic strategies againstBurkholderia cepaciacomplex (BCC) colonization in cystic fibrosis (CF). We assessed the impact of cysteamine (Lynovex) in combination with standard-of-care CF antibioticsin vitroagainst BCC CF isolates by the concentration at which 100% of bacteria were killed (MIC100) and checkerboard assays under CLSI standard conditions. Cysteamine facilitated the aminoglycoside-, fluoroquinolone- and folate pathway inhibitor-mediated killing of BCC organisms that were otherwise resistant or intermediately sensitive to these antibiotic classes. Slow-growing BCC strains are often recalcitrant to treatment and form biofilms. In assessing the impact of cysteamine on biofilms, we demonstrated inhibition of BCC biofilm formation at sub-MIC100s of cysteamine.

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Multiple combination bactericidal testing for patients with cystic fibrosis infected with Burkholderia cepacia before and after lung transplantation

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2003.11.148 ◽

2004 ◽

Vol 23 (2) ◽

pp. S91

Author(s):

A.R Scott ◽

J.M Morton ◽

C Harbour ◽

B Rose ◽

M Robinson ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Transplantation ◽

Burkholderia Cepacia ◽

Before And After

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Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients

Russian Medical Inquiry ◽

10.32364/2587-6821-2021-5-7-462-467 ◽

2021 ◽

Vol 5 (7) ◽

pp. 462-467

Author(s):

V.R. Makhmutova ◽

◽

T.E. Gembitskaya ◽

A.G. Chermensky ◽

O.N. Titova ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Burkholderia Cepacia ◽

Fatal Outcome ◽

Burkholderia Cepacia Complex ◽

Diffusion Method ◽

Achromobacter Xylosoxidans ◽

Disk Diffusion Method ◽

Resistance Monitoring

Aim: to evaluate the infection rate and resistance of isolated Achromobacter xylosoxidans to carbapenems in adult cystic fibrosis patients (CF). Patients and Methods: a retrospective analysis of the results of culture test and time-of-flight mass spectrometry MALDI-TOF was conducted: 685 sputum samples of 58 adult CF patients for a period of 5 years (2016–2020). To assess the sensitivity to imipenem and meropenem, the agar gradient diffusion and disk diffusion method were used. Results: the incidence of infection with A. xylosoxidans in adult CF patients for the period from 2016 to 2020 when monitoring a single sample of patients (n=24) to evaluate the occurrence of this pathogen with increasing age ranged from 16.6% in 2016–2017, increasing to 37.5% in 2018–2019, and with a further reduction to 20.8% (associated with disease fatal outcome in 3 of the 9 infected patients). There was no statistically significant dependence of the fatal outcome on infection with A. xylosoxidans. When analyzing the entire pool of patients (n=58) from 2016 to 2020, the release frequency of Pseudomonas aeruginosa remains approximately the same, varying from 63.3% to 46.5% and maintaining a numerical advantage in all follow-up periods, while the A. xylosoxidans infection ranges from 13.7% to 39.3%. In 2016–2018, 50% of isolates were sensitive to carbapenems, in 2018 — 53.8% of isolates, in 2019–2020 — the activity of obtained isolates decreased to 37.5% and 30.7%, respectively. Conclusion: despite the dynamics of indicators and the sample size, the dynamics over 5 years maintained a group-wide proportion of microbiome species dominated primarily by Pseudomonas infection and A. xylosoxidans. In our follow-up, the activity of carbapenems in relation to A. xylosoxidans has almost halved. KEYWORDS: cystic fibrosis, Burkholderia cepacia complex, Achromobacter xylosoxidans, Pseudomonas aeruginosa, lethality, antibiotic resistance, carbapenems. FOR CITATION: Makhmutova V.R., Gembitskaya T.E., Chermensky A.G. et al. Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients. Russian Medical Inquiry. 2021;5(7):462–467 (in Russ.). DOI: 10.32364/2587-6821-2021-5-7-462-467.

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