scholarly journals Management of initial colonisations with Burkholderia species in France, a retrospective analysis in five Cystic Fibrosis Centres

2020 ◽  
Author(s):  
Vianney Gruzelle ◽  
Hélène Guet-Revillet ◽  
Christine Segonds ◽  
Stéphanie Bui ◽  
Julie Macey ◽  
...  

Abstract Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome. We performed a retrospective review of the primary colonisations (PC) observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected. Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher FEV1 and FVC at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. Thus, the management of PC was shown to be heterogeneous, and the statistic power of our study insufficient. Large prospective studies are needed to define who to treat, when, and how. Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia one month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of IV beta-lactam + oral or IV fluoroquinolone + inhaled aminoglycoside.

2019 ◽  
Author(s):  
Vianney Gruzelle ◽  
Hélène Guet-Revillet ◽  
Christine Segonds ◽  
Stéphanie Bui ◽  
Julie Macey ◽  
...  

Abstract Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome. We performed a retrospective review of the primary colonisations (PC) observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected. Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher FEV1 and FVC at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. Thus, the management of PC was shown to be heterogeneous, and the statistic power of our study insufficient. Large prospective studies are needed to define who to treat, when, and how. Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia one month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of IV beta-lactam + oral or IV fluoroquinolone + inhaled aminoglycoside.


2020 ◽  
Author(s):  
Vianney Gruzelle ◽  
Hélène Guet-Revillet ◽  
Christine Segonds ◽  
Stéphanie Bui ◽  
Julie Macey ◽  
...  

Abstract Background: Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome. Methods: We performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected. Results: Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in one second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how. Conclusion: Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia one month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of IV beta-lactam + oral or IV fluoroquinolone + inhaled aminoglycoside.


2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Vidya P. Narayanaswamy ◽  
Andrew P. Duncan ◽  
John J. LiPuma ◽  
William P. Wiesmann ◽  
Shenda M. Baker ◽  
...  

ABSTRACT Burkholderia cepacia complex (Bcc) lung infections in cystic fibrosis (CF) patients are often associated with a steady decline in lung function and death. The formation of biofilms and inherent multidrug resistance are virulence factors associated with Bcc infection and contribute to increased risk of mortality in CF patients. New therapeutic strategies targeting bacterial biofilms are anticipated to enhance antibiotic penetration and facilitate resolution of infection. Poly (acetyl, arginyl) glucosamine (PAAG) is a cationic glycopolymer therapeutic being developed to directly target biofilm integrity. In this study, 13 isolates from 7 species were examined, including Burkholderia multivorans, Burkholderia cenocepacia, Burkholderia gladioli, Burkholderia dolosa, Burkholderia vietnamiensis, and B. cepacia. These isolates were selected for their resistance to standard clinical antibiotics and their ability to form biofilms in vitro. Biofilm biomass was quantitated using static tissue culture plate (TCP) biofilm methods and a minimum biofilm eradication concentration (MBEC) assay. Confocal laser scanning microscopy (CLSM) visualized biofilm removal by PAAG during treatment. Both TCP and MBEC methods demonstrated a significant dose-dependent relationship with regard to biofilm removal by 50 to 200 μg/ml PAAG following a 1-h treatment (P < 0.01). A significant reduction in biofilm thickness was observed following a 10-min treatment of Bcc biofilms with PAAG compared to that with vehicle control (P < 0.001) in TCP, MBEC, and CLSM analyses. PAAG also rapidly permeabilizes bacteria within the first 10 min of treatment. Glycopolymers, such as PAAG, are a new class of large-molecule therapeutics that support the treatment of recalcitrant Bcc biofilm.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Dale M. Mazer ◽  
Carol Young ◽  
Linda M. Kalikin ◽  
Theodore Spilker ◽  
John J. LiPuma

ABSTRACT We tested the activities of ceftolozane-tazobactam and 13 other antimicrobial agents against 221 strains of Burkholderia cepacia complex and Burkholderia gladioli. Most strains (82%) were cultured from persons with cystic fibrosis, and most (85%) were recovered since 2011. The ceftolozane-tazobactam MIC was ≤8 μg/ml for 77% of the strains. However, the MIC range was broad (≤0.5 to >64 μg/ml; MIC50/90, 2/32 μg/ml). Significant differences in susceptibility to some antimicrobial agents were observed between species.


2014 ◽  
Vol 82 (11) ◽  
pp. 4729-4745 ◽  
Author(s):  
Ute Schwab ◽  
Lubna H. Abdullah ◽  
Olivia S. Perlmutt ◽  
Daniel Albert ◽  
C. William Davis ◽  
...  

ABSTRACTThe localization ofBurkholderia cepaciacomplex (Bcc) bacteria in cystic fibrosis (CF) lungs, alone or during coinfection withPseudomonas aeruginosa, is poorly understood. We performed immunohistochemistry for Bcc andP. aeruginosabacteria on 21 coinfected or singly infected CF lungs obtained at transplantation or autopsy. Parallelin vitroexperiments examined the growth of two Bcc species,Burkholderia cenocepaciaandBurkholderia multivorans, in environments similar to those occupied byP. aeruginosain the CF lung. Bcc bacteria were predominantly identified in the CF lung as single cells or small clusters within phagocytes and mucus but not as “biofilm-like structures.” In contrast,P. aeruginosawas identified in biofilm-like masses, but densities appeared to be reduced during coinfection with Bcc bacteria. Based on chemical analyses of CF and non-CF respiratory secretions, a test medium was defined to study Bcc growth and interactions withP. aeruginosain an environment mimicking the CF lung. When test medium was supplemented with alternative electron acceptors under anaerobic conditions,B. cenocepaciaandB. multivoransused fermentation rather than anaerobic respiration to gain energy, consistent with the identification of fermentation products by high-performance liquid chromatography (HPLC). Both Bcc species also expressed mucinases that produced carbon sources from mucins for growth. In the presence ofP. aeruginosain vitro, both Bcc species grew anaerobically but not aerobically. We propose that Bcc bacteria (i) invade aP. aeruginosa-infected CF lung when the airway lumen is anaerobic, (ii) inhibitP. aeruginosabiofilm-like growth, and (iii) expand the host bacterial niche from mucus to also include macrophages.


2016 ◽  
Vol 60 (10) ◽  
pp. 6200-6206 ◽  
Author(s):  
Douglas Fraser-Pitt ◽  
Derry Mercer ◽  
Emma Lovie ◽  
Jennifer Robertson ◽  
Deborah O'Neil

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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