scholarly journals In VitroEfficacy of High-Dose Tobramycin against Burkholderia cepacia Complex and Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

2014 ◽  
Vol 59 (1) ◽  
pp. 711-713 ◽  
Author(s):  
Anina Ratjen ◽  
Yvonne Yau ◽  
Jillian Wettlaufer ◽  
Larissa Matukas ◽  
James E. A. Zlosnik ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Outcomes ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Burkholderia Cepacia Complex ◽  
High Dose ◽  
Content Type ◽  
Planktonic Growth ◽  
Inhalation Devices

ABSTRACTBurkholderia cepaciacomplex andStenotrophomonas maltophiliainfections are associated with poor clinical outcomes in persons with cystic fibrosis (CF). The MIC50based on planktonic growth and the biofilm concentration at which 50% of the isolates tested are inhibited (BIC50) of tobramycin were measured for 180B. cepaciacomplex and 101S. maltophiliaCF isolates and were 100 μg/ml for both species. New inhalation devices that deliver high tobramycin levels to the lung may be able to exceed these MICs.

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

2015 ◽  
Vol 60 (1) ◽  
pp. 348-355 ◽  
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.

scholarly journals Differential Persistence among Genomovars of the Burkholderia cepacia Complex in a Murine Model of Pulmonary Infection

2002 ◽  
Vol 70 (5) ◽  
pp. 2715-2720 ◽  
Author(s):  
Karen K. Chu ◽  
Donald J. Davidson ◽  
T. Keith Halsey ◽  
Jacqueline W. Chung ◽  
David P. Speert
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Outcomes ◽  
Murine Model ◽  
Burkholderia Cepacia ◽  
Pulmonary Infection ◽  
Burkholderia Cepacia Complex ◽  
Clinical Infection ◽  
Minimal Toxicity

ABSTRACT Cystic fibrosis patients infected with strains from different genomovars of the Burkholderia cepacia complex can experience diverse clinical outcomes. To identify genomovar-specific determinants that might be responsible for these differences, we developed a pulmonary model of infection in BALB/c mice. Mice were rendered leukopenic by administration of cyclophosphamide prior to intranasal challenge with 1.6 × 104 bacteria. Five of six genomovar II strains persisted at stable numbers in the lungs until day 16 with minimal toxicity, whereas zero of seven genomovar III strains persisted but resulted in variable toxicity. We have developed a chronic pulmonary model of B. cepacia infection which reveals differences among genomovars in terms of clinical infection outcome.

scholarly journals Epidemiology of cystic fibrosis respiratory pathogens isolated at a South African Hospital, 2006–2010

2016 ◽  
Vol 31 (4) ◽  
pp. 106-111
Author(s):  
Vindana Chibabhai ◽  
Warren Lowman
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
South African ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Burkholderia Cepacia Complex ◽  
Respiratory Pathogens ◽  
Academic Hospital ◽  
Cystic Fibrosis Population ◽  
Susceptibility Patterns

Background: The epidemiology of cystic fibrosis (CF) associated pathogens other than Pseudomonas aeruginosa in the South African cystic fibrosis population has not been previously described.Methods: A retrospective review of respiratory cultures taken from cystic fibrosis clinic patients at the Charlotte Maxeke Johannesburg Academic Hospital from 2006 to 2010 was performed.Results: During the study period, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia complex and Candida albicans prevalence remained stable, Aspergillus fumigatus increased from 8% to 20% (p = 0.0132); Staphylococcus aureus decreased from 66% to 50% (p = 0.0243) and Haemophilus influenzae decreased from 13% to 3% (p = 0.0136). There were significant antimicrobial susceptibility changes to meropenem (p  0.0001) amongst P. aeruginosa isolates and cloxacillin (p 0.0001) amongst S. aureus isolates. Prevalence of most bacterial pathogens appeared to increase with increasing age.Conclusion: The findings of this study illustrate the epidemiology of CF associated respiratory pathogens and the trends in prevalence and susceptibility patterns over a 5-year period.

scholarly journals In Vitro Activity of a Novel Glycopolymer against Biofilms of Burkholderia cepacia Complex Cystic Fibrosis Clinical Isolates

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Vidya P. Narayanaswamy ◽  
Andrew P. Duncan ◽  
John J. LiPuma ◽  
William P. Wiesmann ◽  
Shenda M. Baker ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Laser Scanning Microscopy ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Confocal Laser ◽  
Content Type ◽  
Biofilm Removal ◽  
Increased Risk

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.

scholarly journals Biofilm Compared to Conventional Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

2013 ◽  
Vol 57 (3) ◽  
pp. 1546-1548 ◽  
Author(s):  
Kitty Wu ◽  
Yvonne C. W. Yau ◽  
Larissa Matukas ◽  
Valerie Waters
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Dose ◽  
Content Type

ABSTRACTStenotrophomonas maltophiliais a multidrug-resistant organism increasingly isolated from the lungs of cystic fibrosis (CF) patients. One hundred twenty-fiveS. maltophiliaisolates from 85 CF patients underwent planktonic and biofilm susceptibility testing against 9 different antibiotics, alone and in double antibiotic combinations. WhenS. maltophiliaisolates were grown as a biofilm, 4 of the 10 most effective antibiotic combinations included high-dose levofloxacin and 7 of the 10 combinations included colistin at doses achievable by aerosolization.

scholarly journals Is the Potable Water System an Advantageous Preinfection Niche for Bacteria Colonizing the Cystic Fibrosis Lung?

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Matthew J. Wargo
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Potable Water ◽  
Water System ◽  
Achromobacter Xylosoxidans ◽  
Low Oxygen ◽  
Content Type ◽  
Lung Infections ◽  
Successful Colonization

ABSTRACTPeople with cystic fibrosis are susceptible to lung infections from a variety of bacteria, a number of which also reside in the potable water system, includingPseudomonas aeruginosa,Stenotrophomonas maltophilia,Achromobacter xylosoxidans,Burkholderia cepaciacomplex, and nontuberculosisMycobacteria. Here, I propose chemical and physical aspects of the potable water system along with bacterial lifestyle strategies in this system that may enhance successful colonization of cystic fibrosis lungs by these bacteria, including iron and copper levels, lipids, and low growth rates within low-oxygen biofilms.

scholarly journals Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

2016 ◽  
Vol 84 (5) ◽  
pp. 1424-1437 ◽  
Author(s):  
Siobhán McClean ◽  
Marc E. Healy ◽  
Cassandra Collins ◽  
Stephen Carberry ◽  
Luke O'Shaughnessy ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Burkholderia Cepacia ◽  
Therapeutic Option ◽  
Lung Epithelial Cells ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Content Type ◽  
Lung Epithelial ◽  
Proteomics Approach

Members of theBurkholderia cepaciacomplex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species:Burkholderia cenocepacia, the most virulent, andB. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species.Escherichia colistrains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responsesin vivo. Mice immunized with either recombinant linocin or OmpW were protected fromB. cenocepaciaandB. multivoranschallenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

scholarly journals In Vitro Activity of Ceftolozane-Tazobactam and Other Antimicrobial Agents against Burkholderia cepacia Complex and Burkholderia gladioli

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Dale M. Mazer ◽  
Carol Young ◽  
Linda M. Kalikin ◽  
Theodore Spilker ◽  
John J. LiPuma
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Antimicrobial Agents ◽  
Vitro Activity ◽  
Burkholderia Cepacia Complex ◽  
In Vitro Activity ◽  
Content Type ◽  
Burkholderia Gladioli

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.

scholarly journals Localization of Burkholderia cepacia Complex Bacteria in Cystic Fibrosis Lungs and Interactions with Pseudomonas aeruginosa in Hypoxic Mucus

2014 ◽  
Vol 82 (11) ◽  
pp. 4729-4745 ◽  
Author(s):  
Ute Schwab ◽  
Lubna H. Abdullah ◽  
Olivia S. Perlmutt ◽  
Daniel Albert ◽  
C. William Davis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Burkholderia Cepacia ◽  
Single Cells ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Test Medium ◽  
Fermentation Products ◽  
Content Type

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.

scholarly journals Activity of Cysteamine against the Cystic Fibrosis Pathogen Burkholderia cepacia Complex

2016 ◽  
Vol 60 (10) ◽  
pp. 6200-6206 ◽  
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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