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

Abstract

f 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 g/ml of tobramycin for Burkholderia cepacia, Burkholderia multivorans, and Burkholderia vietnamiensis; 200 g/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 g/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 g/ml for B. cepacia and B. dolosa (24 h) and >100 g/ml for Burkholderia cenocepacia and B. dolosa (48 h). Although sputum significantly increased biofilm thickness, tobramycin concentrations of 1,000 g/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 g/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.

Burkholderia cenocepacia Infections in Cystic Fibrosis Patients: Drug Resistance and Therapeutic Approaches

“… Kennedy et al (2015) showed the efficacy of high-dose tobramycin in reducing Burkholderia biofilm thickness in vitro , suggesting a possible role as a suppressive therapy in CF. Subsequently, a pilot, open-label clinical trial of TOBI Podhaler administered twice daily for 28 days in adults and children with CF and chronic B. cepacia complex infection was carried out ( Waters et al, 2017 ).…”

Antibiotics susceptibility of Burkholderia species of Sarawak origin

“…However, unlike what has been reported in other melioidosis endemic countries, over 80% B. pseudomallei strains in Sarawak were found to be susceptible towards aminoglycosides and macrolides (Podin et al, 2014). Apart from a previous report of B. cepacia being resistant to tobramycin (Kennedy et al, 2015), there is little knowledge on the antibiotics susceptibility profile of other Burkholderia spp.…”

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

“…The latest ceftazidime-avibactam combination therapy seems promising but insufficient clinical experience has been acquired to date [36]. In spite of the natural resistance to aminoglycosides, the use of inhaled tobramycin which allows the delivery of high doses are considered to be of interest in BCC infections [24], [25]. B. gladioli is generally slightly more susceptible than BCC, especially to piperacillintazobactam and aminoglycosides [17].…”

“…Once data collection had been completed, the susceptibility of the last strain recovered before the onset of treatment was tested by the OBC, for each antibiotic administered, following the guidelines of the antibiogram committee of the French Society for Microbiology, and using PK-PD breakpoints, or species related breakpoints when available [23]. In the absence of specific values for inhaled aztreonam-lysine, the breakpoints for parenteral administration were used, whereas inhaled tobramycin was considered active given the high pulmonary concentrations delivered [24,25]. The consistency of eradication treatments with in vitro antibiotic susceptibilities or recognized activity (inhaled tobramycin) was then analysed for each patient treated.…”