Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Sponsor: Gilead Sciences


The purpose of this research study is to see if an experimental drug called Aztreonam for Inhalation Solution is safe and effective to treat Burkholderia lung infections in patients with Cystic fibrosis.

Drug: Aztreonam for Inhalation solution

Study Type: Phase III

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Official Title:
Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trail to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis(CF) and Chronic Burkholderia Species Infection

Primary Outcome Measures:
Change from baseline in FEV1 percent predicted as measured by the AUCave through week 24.

Secondary Outcome Measures:
AUCave of relative change from baseline in FEV1, FVC, and FEF25 to 75 percent through week 24.

Estimated Enrollment:
76

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.
lactose and sodium chloride: Placebo Comparator

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.

Eligibility

Ages Eligible for Study:
6 Years and older

Inclusion Criteria:
Male or female ≥ 6 years of age

Subjects with CF as diagnosed by one of the following:
Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
Documented sweat sodium ≥ 60 mmol/L
Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Abnormal NPD with accompanying symptoms characteristic of CF

Chronic infection with Burkholderia spp. defined by:
One sputum culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
At least 50% of sputum cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
At least one positive sputum culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory)

Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment.

Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction on their aerosolized antibiotic treatment

Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed

Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures

Ability to perform reproducible pulmonary function tests

Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner

Exclusion Criteria:
Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
Administration of AZLI treatment within the 28 days prior to randomization/baseline

Known local or systemic hypersensitivity to monobactam antibiotics

History of lung transplantation

Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
AST or ALT > 5 times upper limit of normal (ULN) range
Serum creatinine > 2 times ULN

Known portal hypertension or complications of CF hepatopathy

Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested

Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8

Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01059565
Contacts
Contact: Sheila Leitzinger
2062564904
sheila.leitzinger@gilead.com
Contact: Jennifer Glover
2067923039
jennifer.glover@gilead.com Hide Study Locations

Locations

United States, Alabama
Pulmonary Associates of Mobile, P.C.
Mobile, Alabama, United States, 36608

United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016

United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205

United States, California
University of Southern California
Los Angeles, California, United States, 90033

United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206

United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102

United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803

United States, Florida
Tampa General Hospital
Tampa, Florida, United States, 33606

University of Miami
Miami, Florida, United States, 33136
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207

United States, Illinois
The Cystic Fibrosis Institute
Glenview, Illinois, United States, 60025

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
UMass Medical Center
Worcester, Massachusetts, United States, 01605

United States, Michigan
Harper University Hospital/Wayne State University
Detroit, Michigan, United States, 48201
University of Michigan
Ann Arbor, Michigan, United States, 48109

United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455

United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

United States, Nevada
Childrens Lung Specialists
Las Vegas, Nevada, United States, 89107

United States, New Jersey
Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903

Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962

United States, New Mexico
Univesity of New Mexico
Albuquerque, New Mexico, United States, 87131

United States, New York
The Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040

United States, North Carolina
UNC Chapel Hill
Chapel Hill, North Carolina, United States, 27599

United States, Ohio
Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308
Toledo Children's Hospital/The Toledo Hospital
Toledo, Ohio, United States, 43606

United States, Oklahoma
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, United States, 73112

United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States, 97239

Kaiser Permanente Northwest
Portland, Oregon, United States, 97227

United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15201
Penn State Inst & Milton S. Hershey Med Ctr
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina
MUSC
Charleston, South Carolina, United States, 29425

University of South Carolinas School of Medicine
Columbia, South Carolina, United States, 29203

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298

Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507

United States, West Virginia
Pediatric Infectious Diseases
Morgantown, West Virginia, United States, 26506

United States, Wisconsin
Medical College of Wisconsin, Children's Hospital Wisconsin
Milwaukee, Wisconsin, United States, 53201

Canada, Ontario
St Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8

Trends in pathogens colonising the respiratory tract of adult patients with cystic fibrosis, 1985-2005.

J Cyst Fibros. 2009 Sep 7. [Epub ahead of print]

Trends in pathogens colonising the respiratory tract of adult patients with cystic fibrosis, 1985-2005.

Millar FA, Simmonds NJ, Hodson ME.

Adult Cystic Fibrosis Dept, NHLI/Imperial College and Royal Brompton Hospital, London, United Kingdom.

INTRODUCTION: The treatment of patients with CF has continued to evolve. We hypothesised that sputum microbiology may have changed as a result of this.

METHOD: Retrospective analysis of sputum microbiology from adult CF patients (1985 to 2005) using the Royal Brompton Hospital CF database.

RESULTS: Colonisation with Pseudomonas aeruginosa or Staphylococcus aureus between 1985 and 2005 remained stable (77 to 82%, p=0.159; 54 to 47%, p=0.108; respectively). Haemophilus influenzae (48 to 6%; p<0.001), Aspergillus species (18 to 9%; p=0.002) and Burkholderia cepacia complex (9 to 4%; p=0.041) prevalence decreased. Stenotrophomonas maltophilia and MRSA increased (1 to 4%, p=0.02; 1 to 6%, p=0.002, respectively).

CONCLUSION: P. aeruginosa colonisation has remained stable; there has been a decline in B. cepacia complex, H. influenzae and Aspergillus sp., and only a small increase in S. maltophilia and MRSA. Intensive antibiotic strategies have been employed, which, so far, have not resulted in clinically significant emergence of new pathogens.

Liposomal Tobramycin Receives Second Orphan Drug Designation Within Weeks

ZURICH, July 16 /PRNewswire/ -- An innovative treatment for infections of the respiratory tract in cystic fibrosis patients has received a second orphan drug designation in the US only weeks after a first designation was granted. The recent designation relates to Burkholderia cepacia pathogens that can cause lethal infections in cystic fibrosis patients. For Axentis Pharma AG of Zurich, Switzerland, both designations affirm the therapeutic potential of its product candidate Fluidosomes(TM)-tobramycin, whose unique microbiological profile sets it apart from other antibiotic formulations (including free tobramycin).

Axentis Pharma (Switzerland) announced today that the Office of Orphan Products Development of the US Food and Drug Administration (FDA) has granted a second orphan drug designation to its lead product candidate Fluidosomes(TM)-tobramycin. This drug is a liposomal formulation of tobramycin and an innovative treatment for infections of the respiratory tract in patients with cystic fibrosis. Only three months ago, the FDA granted Fluidosomes(TM)-tobramycin orphan drug designation for the treatment of pulmonary infections caused by Pseudomonas aeruginosa. The newly granted second designation relates to pulmonary infections caused by Burkholderia cepacia (B. cepacia) pathogens.

Despite stringent infection control practices, B. cepacia infections still occur in cystic fibrosis patients and can lead to fatal sepsis. The cell envelopes of these especially virulent bacteria are impermeable to most antibiotics, which makes them particularly difficult to treat. Due to its unique mode of action, which allows the antibiotics to penetrate into the bacteria, Fluidosomes(TM)-tobramycin could become a particularly effective treatment for B. cepacia infections.

Prof. Dr. Miguel A Valvano, MD, Medical Advisor to Axentis Pharma, comments on the development: "Burkholderia cepacia is almost always multi-resistant to antibiotics and this, in conjunction with the poor prognosis of patients with B. cepacia infection, makes the treatment of these patients exceedingly complex. Tobramycin is in principle an effective antibiotic. The drug is however rather ineffective due to the impermeability of B. cepacia's cell envelope. In addition, B. cepacia - just like many other pathogens - has developed mechanisms to eliminate antibiotics once they have entered the cell. Fluidosomes(TM)-tobramycin seems to overcome these limitations by packing tobramycin into liposomes, which, by allowing effective penetration of the antibiotic into the bacterial cell, completely changes the microbiological profile of this antibiotic. Hence, Fluidosomes(TM)-tobramycin could be a totally new antibiotic formulation that addresses microbiological needs that no other antibiotic can."

What exactly happens when Fluidosomes(TM)-tobramycin encounters the bacterium is still not entirely clear, but pre-clinical data indicate a novel mode of action. Dr. Helmut Brunar, CEO of Axentis Pharma explains: "Once at the site of infection, tobramycin-containing liposomes seem to fuse with the cell membrane of the pathogen. In this way, the entire load of tobramycin contained in the Fluidosomes(TM) is released into the bacterial cell. Additionally, our data indicate that bacterial rescue mechanisms that pump tobramycin out of the cell are inhibited by the fusion process. The efficient delivery and maximum release of tobramycin into the bacterial cell together with inhibition of the clearance mechanism indicate that Fluidosomes(TM)-tobramycin has a highly efficient therapeutic effect."

About Axentis Pharma AG (http://www.axentispharma.com)

Axentis Pharma is a respiratory specialty pharmaceutical company whose core competence is the combination of a fully patented, liposome-based drug delivery system with already established and well-characterized therapeutic agents. The company is using its platform delivery technology, named Fluidosomes(TM) technology, for the development of its lead product, an inhalable liposomal formulation of tobramycin. Axentis Pharma's lead product is designed to treat bacterial infections in the lungs.

About Fluidosomes(TM) technology

Axentis Pharma's Fluidosomes(TM) technology uses biocompatible lipids endogenous to the lung that are formulated into small liposomes. This nanocapsule platform offers wide-ranging potential for unmet medical needs, including chronic respiratory infections of the lung. In the case of Fluidosomes(TM)-tobramycin, the interaction between tobramycin and the microbial cell is triggered when the liposomes undergo a fusion process with the outer membrane of the bacterial cell wall. Tobramycin then penetrates into the inner cell compartment and triggers bacterial cell death.

   
   For further information, please contact:
   Dr. Helmut Brunar, Ph.D., CEO
   Axentis Pharma AG
   Limmatquai 138
   8001 Zurich, Switzerland
   T +41-44-202-7878
   E board@axentispharma.com
   W http://www.axentispharma.com

   Copy Editing & Distribution:
   PR&D - Public Relations for Research & Education
   Campus Vienna Biocenter 2
   1030 Vienna, Austria
   T +43-1-505-70-44
   E contact@prd.at
   W http://www.prd.at

Isolation of Burkholderia cenocepacia and Burkholderia vietnamiensis from sewage. Important data for CFers

Int J Environ Health Res. 2009 Apr;19(2):157-62.

Isolation of Burkholderia cenocepacia and Burkholderia vietnamiensis from human sewage.

McNeely D, Moore JE, Elborn JS, Millar BC, Rendall J, Dooley JS.

University of Ulster, Coleraine, UK.

Fresh human sewage was examined from a sewage treatment plant for the presence of members of the Burkholderia cepacia complex (BCC) of bacterial organisms and confirmed the presence of viable B. cenocepacia and B. vietnamiensis, by a combination of cultural, phenotypic and genotypic techniques. Both these organisms are important respiratory pathogens for patients with cystic fibrosis (CF). Presently, the survival dynamics of these organisms in sewage effluent and sludge is, as yet, unknown. Therefore, as this study represents the first report of these CF pathogens in sewage and until such survival data is available, careful risk assessment needs to be undertaken in relation to the end use application of potentially contaminated sewage and where such material comes into association with non-colonised patients with cystic fibrosis, so that any potential transmission of these pathogens from sewage to patient is assessed and minimised/eliminated.

Sugar sweet and deadly? Cepacia and CF

Microbiology 155 (2009), 665-666; DOI 10.1099/mic.0.024752-0

Microbiology 155 (2009), 665-666; DOI 10.1099/mic.0.024752-0
© 2009 Society for General Microbiology

Comment

Sugar sweet and deadly?

D. W. Reid¹ and S. C. Bell²

¹ Menzies Research Institute, Hobart, Tasmania, Australia
² The Prince Charles Hospital, Chermside, Brisbane, Queensland, Australia

Correspondence
D. W. Reid
(d.e.c.reid@utas.edu.au)

The recent report by Bartholdson et al. (2008) demonstrating production of large amounts of exopolysaccharide (EPS) by organisms of the Burkholderia cepacia complex (Bcc), which changed the phenotype from non-mucoid to mucoid when the bacteria were exposed in vitro to a variety of sugar alcohols including mannitol, fructose and sucrose, raises a worrying scenario. Mannitol as an inhaled therapy appears to increase the hydration of airway secretions and thus promote airway clearance, with demonstrated improvements in lung function (Jaques et al., 2008; Minasian et al., 2007). As Bartholdson and colleagues highlight, cystic fibrosis (CF) patients infected with Bcc have been excluded from the clinical trials of mannitol in order not to confound results, given the potential adverse impact of some of these strains on lung function decline. In Australia, 4.1 % of all CF individuals are infected with Bcc, but the prevalence rises with increasing age (Australian CF Data Registry Report 2005). Similar or higher prevalence of Bcc infection has been reported from Europe, the USA and Canada (Lambiase et al., 2006). The obvious concern is that despite the findings of Bartholdson and colleagues, mannitol will be prescribed in Bcc-infected patients. The large multi-centre studies of hypertonic saline (Elkins et al., 2006) and azithromycin (Saiman et al., 2003) have also excluded patients with Bcc infection; however, these treatments are now frequently prescribed in this patient population (unpublished observations). Interestingly, strains of the more virulent ET12 strain of Burkholderia cenocepacia did not produce EPS following growth on mannitol, and the critical determinant here appears to be the bce gene cluster, with ET12 strains possessing an 11 bp deletion that prevented bce upregulation by mannitol and thus EPS production. Paradoxically therefore, mannitol may not be of great concern when administered to patients infected with the ET12 strain, but may have adverse consequences when used in the setting of what are generally considered less virulent strains.

View this table: [in this window] [in a new window]

The other consideration from a microbiological perspective prompted by the study of Bartholdson and colleagues is the impact of increased sugar moiety availability to Bcc in the setting of CF-related diabetes (CFRD). To our knowledge, no comprehensive longitudinal study has been undertaken of the impact of CFRD on Bcc infection. Insulin therapy for CFRD has been shown to improve lung function and nutritional indices as well as reduce the prevalence of positive sputum cultures for Streptococcus pneumoniae and Haemophilus influenzae, suggesting that abnormal glucose homeostasis may promote infection in CF (Lanng et al., 1994). Assessment of sugar moieties has not been undertaken in CF sputum, but levels of fructose and other sugar alcohols are elevated in the serum of patients with diabetes and are likely to be similarly increased in airway secretions in patients with CFRD, providing a favourable substrate for bacterial growth (Kawasaki et al., 2002). The findings of Bartholdson and colleagues would also suggest that the lungs of patients with CFRD may promote bacterial virulence, i.e. EPS production by Bcc. Careful analysis of the impact of CFRD on CF patients with Bcc infection is required but will need international collaboration to ensure sufficient patient numbers to provide statistical power. New therapies such as mannitol will require close scrutiny in patients with Bcc infection, although the evidence indicates that this therapy will be of benefit in those infected with P. aeruginosa, who constitute the vast majority of the CF population.

REFERENCES

Bartholdson, S. J., Brown, A. R., Mewburn, B. R., Clarke, D. J., Fry, S. C., Campopiano, D. J. & Govan, J. R. (2008). Plant host and sugar alcohol induced exopolysaccharide biosynthesis in the Burkholderia cepacia complex. Microbiology 154, 2513–2521.[Abstract/Free Full Text]

Elkins, M. R., Robinson, M., Rose, B. R., Harbour, C., Moriarty, C. P., Marks, G. B., Belousova, E. G., Xuan, W. & Bye, P. T. (2006). A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 354, 229–240.[Abstract/Free Full Text]

Jaques, A., Daviskas, E., Turton, J. A., McKay, K., Cooper, P., Stirling, R. G., Robertson, C. F., Bye, P. T., Lesouëf, P. N. & other authors (2008). Inhaled mannitol improves lung function in cystic fibrosis. Chest 133, 1388–1396.[CrossRef][Medline]

Kawasaki, T., Akanuma, H. & Yamanouchi, T. (2002). Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 25, 353–357.[Abstract/Free Full Text]

Lambiase, A., Raia, V., Del Pezzo, M., Sepe, A., Carnovale, V. & Rossano, F. (2006). Microbiology of airway disease in a cohort of patients with cystic fibrosis. BMC Infect Dis 6, 4[CrossRef][Medline]

Lanng, S., Thorsteinsson, B., Nerup, J. & Koch, C. (1994). Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections. Acta Paediatr 83, 849–853.[Medline]

Minasian, C. C., Wallis, C. & Bush, A. (2007). Mannitol as a mucolytic in cystic fibrosis. J R Soc Med 100 (Suppl. 47), 53–56.[Medline]

Saiman, L., Marshall, B. C., Mayer-Hamblett, N., Burns, J. L., Quittner, A. L., Cibene, D A., Coquillette, S., Fieberg, A. Y., Accurso, F. J. & other authors (2003). Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 290, 1749–1756.[Abstract/Free Full Text]

Related Articles

Sugar sweet and deadly: author's response

John R. W. Govan
Microbiology 2009 155: 666. [Full Text] [PDF]

Plant host and sugar alcohol induced exopolysaccharide biosynthesis in the Burkholderia cepacia complex

S. Josefin Bartholdson, Alan R. Brown, Ben R. Mewburn, David J. Clarke, Stephen C. Fry, Dominic J. Campopiano, and John R. W. Govan
Microbiology 2008 154: 2513-2521. [Abstract] [Full Text] [PDF]

http://snipurl.com/fn89b

Superbug complicates treatment of infections in cystic fibrosis (Cepacia people, PLEASE READ)

A must read for cepacia patients....

Superbug complicates treatment of infections in cystic fibrosis

The unexpected behaviour of a family of "superbugs" called the Burkholderia cepacia complex (Bcc) could have implications for the treatment of cystic fibrosis (CF) patients. CF patients produce large quantities of sticky mucus in their lungs that is difficult to expel and is easily infected by bacteria. A recent treatment for CF, inhalation of a sugar called mannitol, works by attracting moisture into the lungs. This thins the mucus making it easier to disperse. However, recent research by Professor John Govan and colleagues at the University of Edinburgh, published in the journal Microbiology has shown that when Bcc bacteria are grown on mannitol they produce a sticky substance called exopolysaccharide (EPS) which could contribute to the very problem that the mannitol therapy was designed to solve.

Infections caused by slime-producing bacteria are particularly difficult to treat in CF patients. The bacterial slime combines with the debris of the body's own defence cells to form a biofilm which protects the bacteria against both natural defences and antibiotics. And Bcc is an especially virulent bug.

"Burkholderia make other superbugs look like wimps", said Professor Govan, "They not only have larger genomes (hence genetic potential) and are resistant to almost all antibiotics, they can even use antibiotics such as penicillin as a nutrient. One of the problems is that when they are grown under normal laboratory conditions they do not produce the exopolysaccharide slime so their potential for causing serious infection may have been underestimated. We grew them on onion tissue – they were first identified in the 1950's as the cause of onion rot – and found that then they produced copious amounts of slime. Onion tissue contains a lot of simple sugars, including mannitol".

Since Professor Govan's work was published, further potential complications in CF patients caused by the Burkholderia bacteria have been identified. Commenting on the work in the current issue of Microbiology, Dr David Reid, from the Menzies Research Institute, Hobart, Australia, and Dr Scott Bell from The Prince Charles Hospital, Brisbane, Australia, have suggested that the increased levels of sugar in the blood of CF patients with diabetes could contribute to Burkholderia infections.

"CF-related diabetes affects almost one-third of adults with CF", said Dr Reid, "But no comprehensive studies have been carried out to investigate the effect of diabetes on Burkholderia infection. We will need international collaboration to ensure there are sufficient patient numbers to make any survey statistically significant".

"CF patients known to have Burkholderia infections have been excluded from the clinical trials of mannitol therapy", he went on, "But the obvious concern is that, despite Professor Govan's findings, patients with Burkholderia infections will be prescribed mannitol – because mannitol works very well for CF patients with infections caused by a bug called Pseudomonas aeruginosa which consitute the vast majority of the CF population".

In a further twist to the tale, one of the most virulent strains of Burkholderia lacks the gene that causes the bacterium to produce slime – and so CF patients infected with this particular variety might be able to benefit from mannitol therapy. However less virulent Burkholderia strains can use the mannitol to produce slime and make the infections they cause much more severe.

http://www.eurekalert.org/pub_releases/2009-03/sfgm-sct031609.php