f Burkholderia cepacia complex and Stenotrophomonas maltophilia infections are associated with poor clinical outcomes in persons with cystic fibrosis (CF). The MIC 50 based on planktonic growth and the biofilm concentration at which 50% of the isolates tested are inhibited (BIC 50 ) of tobramycin were measured for 180 B. cepacia complex and 101 S. maltophilia CF isolates and were 100 g/ml for both species. New inhalation devices that deliver high tobramycin levels to the lung may be able to exceed these MICs. As individuals with cystic fibrosis (CF) age, they are increasingly infected in their lungs with multidrug-resistant Gramnegative organisms such as Burkholderia cepacia complex and Stenotrophomonas maltophilia, which are associated with poor clinical outcomes (1-5). Treatment of these infections is difficult (6-9) due to their numerous mechanisms of antimicrobial resistance, including efflux pumps, chromosomally encoded ␤-lactamases, decreased outer membrane permeability, intracellular survival, and biofilm formation (10-12). However, newer inhalational antibiotic therapies have the ability to deliver very high concentrations of drug to the lung, which may be able to overcome some of these mechanisms. One of the new inhalational antibiotics available is tobramycin inhalation powder (TIP), delivered by the Podhaler device, which can achieve up to 1.5-to 2-fold higher sputum tobramycin concentrations (up to 2,000 g/g) than tobramycin inhalation solution (TIS) (13). It is not known whether these higher tobramycin concentrations can overwhelm the efficient efflux pumps known to be present in B. cepacia complex and S. maltophilia (14)(15)(16).In order to determine whether the known pulmonary concentrations of inhaled high-dose tobramycin powder can overcome these inhibitory concentrations, the aim of this study was to measure the inhibitory concentrations of tobramycin for a large collection of B. cepacia complex and S. maltophilia isolates, grown planktonically and in a biofilm, from pediatric and adult CF patients.B. cepacia complex isolates (n ϭ 180) were prospectively collected from sputum samples from CF patients from four study sites, The Hospital for Sick Children (n ϭ 10), St. Michael's Hospital (n ϭ 36), the Cystic Fibrosis Foundation Burkholderia cepacia Research Repository at the University of Michigan (n ϭ 16), and the Canadian Burkholderia cepacia Complex Research and Referral Repository at the University of British Columbia, Vancouver (n ϭ 118). S. maltophilia isolates (n ϭ 101) were obtained from pediatric CF patients at The Hospital for Sick Children in Toronto (n ϭ 67) and from adult CF patients (n ϭ 34) at St. Michael's Hospital in Toronto. All the isolates used in this study were independent strains (1 isolate/patient). Antimicrobial susceptibility testing was performed on isolates grown planktonically by broth microdilution using Clinical and Laboratory Standards Institute (CLSI) guidelines (17). Antimicrobial susceptibility testing was also performed on isolates grown as a biofilm using a mo...

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada. A total of 10 subjects (4 pediatric, 6 adult patients) were treated. There was a mean drop of 1.4 log (CFU/ml) in sputum bacterial density (p=0.01) and sputum IL-8 levels decreased significantly after 28days of TIP (p=0.04). The mean relative change in FEV (L) from Day 0 to Day 28 of TIP administration was a 4.6% increase but this was not statistically significant. The majority of patients (70%) had no or mild adverse events.