cMICs and biofilm inhibitory concentrations (BICs) were measured for 68 cystic fibrosis (CF) Achromobacter isolates for amikacin, aztreonam, colistin, levofloxacin, and tobramycin. With the exception of colistin and levofloxacin, the remaining antibiotics had MIC 90 s, BICs at which 50% of the isolates were susceptible (BIC 50 s), and BICs at which 90% of the isolates were susceptible (BIC 90 s) equal to or above the highest concentrations tested. In a biofilm model, tobramycin was able to significantly increase killing of bacterial cells compared to controls, for intermediate-resistant strains only, at concentrations of 1,000 and 2,000 g/ml.A chromobacter species, previously known as Alcaligenes species, are multidrug-resistant Gram-negative bacteria that have increasingly been isolated from the sputum from cystic fibrosis (CF) patients worldwide (1). Case-control studies have shown increased decline in lung function following pulmonary infection with Achromobacter xylosoxidans (2, 3). As with Burkholderia cepacia complex and Stenotrophomonas maltophilia, A. xylosoxidans species are intrinsically resistant to several classes of antibiotics (4-7). Currently, there are no recommendations for chronic suppressive aerosolized antimicrobial therapies to treat these infections in CF patients. The objectives of this study were thus to examine the effects of antibiotics available for aerosolization against a range of CF Achromobacter species grown planktonically and as biofilms, which are important in CF pulmonary infections.Sixty-eight Achromobacter isolates were collected from CF patients at The Hospital for Sick Children, Toronto, Ontario, Canada (n ϭ 15), and the CF Foundation B. cepacia Research Laboratory and Repository, Ann Arbor, MI (n ϭ 53). The collection of Achromobacter CF isolates included five species: A. xylosoxidans (n ϭ 50), A. denitrificans (n ϭ 3), A. dolens (n ϭ 5), A. insolitus (n ϭ 5), and A. ruhlandii (n ϭ 5). Antimicrobial susceptibility testing was performed on isolates grown planktonically and as biofilms for amikacin, aztreonam, colistin, levofloxacin, and tobramycin, as previously described (8, 9). Five A. xylosoxidans CF isolates with intermediate biofilm inhibitory concentrations (BICs) (defined as Յ800 g/ml tobramycin, representing the mean peak sputum concentration of aerosolized tobramycin [10]) and another 5 isolates from the same species but with high BICs (Ͼ800 g/ml tobramycin) were selected for further study in the biofilm slide chamber model. After 48 h of growth, biofilms were treated with various concentrations of tobramycin (0, 8, 400,
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.
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