Activity of Tobramycin against Cystic Fibrosis Isolates of Burkholderia cepacia Complex Grown as Biofilms.
Pulmonary infection with Burkholderia cepacia complex 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 mature B. cepacia complex 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 for Burkholderia cepacia, Burkholderia multivorans, and Burkholderia vietnamiensis; 200 μg/ml of tobramycin was sufficient to reduce the thickness of Burkholderia dolosa biofilm. With a more mature 48-h biofilm, significant reductions in thickness were seen with tobramycin at concentrations of ≥100 μg/ml for all Burkholderia species. In addition, an increased ratio of dead to live cells was observed in comparison to control with tobramycin concentrations of ≥200 μg/ml for B. cepacia and B. dolosa (24 h) and ≥100 μg/ml for Burkholderia cenocepacia and B. 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 all B. cepacia complex species with the exception of B. vietnamiensis. In the presence of sputum, 1,000 μg/ml of tobramycin significantly increased the dead-to-live ratio only for B. multivorans compared to control. In summary, although killing is attenuated, high-dose tobramycin can effectively decrease the thickness of B. cepacia complex biofilms, even in the presence of sputum, suggesting a possible role as a suppressive therapy in CF.
Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Sarah
S
Kennedy
Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Trevor
T
Beaudoin
Division of Microbiology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Yvonne C W
YC
Yau
Centre for Microbial Host Interactions (CMHI), Institute of Technology Tallaght, Dublin 2 Centre of Applied Science in Health (CASH), Dublin, Ireland.
Emma
E
Caraher
Division of Infectious Diseases, Department of Pediatrics, Centre for Understanding and Preventing Infection in Children, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
James E A
JE
Zlosnik
Division of Infectious Diseases, Department of Pediatrics, Centre for Understanding and Preventing Infection in Children, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
David P
DP
Speert
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA.
John J
JJ
LiPuma
Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada.
Elizabeth
E
Tullis
Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada Valerie.waters@sickkids.ca.
Valerie
V
Waters
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D019117:Burkholderia / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D042602:Burkholderia cepacia complex / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D013045:Species Specificity; D013183:Sputum / Q000737:chemistry / Q000382:microbiology; D014031:Tobramycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D014031:Tobramycin