Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients during a recent clinical trial of inhaled tobramycin. Impermeability, in which bacteria have reduced susceptibility to all aminoglycosides, was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or p...

To address limitations in the production of DNA aptamers against small molecules, we introduce a DNA-based capture-SELEX (systematic evolution of ligands by exponential enrichment) protocol with long and continuous randomized library for more flexibility, coupled with in-stream direct-specificity monitoring via SPR and high throughput sequencing (HTS). Applying this capture-SELEX on tobramycin ...

Bacteriophage infection and antibiotics used individually to reduce biofilm mass often result in the emergence of significant levels of phage and antibiotic resistant cells. In contrast, combination therapy in Escherichia coli biofilms employing T4 phage and tobramycin resulted in greater than 99% and 39% reduction in antibiotic and phage resistant cells, respectively. In P. aeruginosa biofilms...

OBJECTIVES We evaluated the suitability of an aminosterol derivative (ASD), possessing interesting in vitro antimicrobial activities against various resistant pathogens involved in lung infections of cystic fibrosis patients, for aerosol drug delivery. METHODS The suitability of 2 and 10 mg/mL ASD solutions for aerosol delivery was evaluated and compared with that of a commercial inhalable so...

Burkholderia cepacia complex and Stenotrophomonas maltophilia infections are associated with poor clinical outcomes in persons with cystic fibrosis (CF). The MIC50 based on planktonic growth and the biofilm concentration at which 50% of the isolates tested are inhibited (BIC50) of tobramycin were measured for 180 B. cepacia complex and 101 S. maltophilia CF isolates and were 100 μg/ml for both ...

We assayed serum gentamicin and tobramycin specimens by the enzyme multiplied immunoassay technique (Syva EMIT) and the fluorescence polarization immunoassay (Abbott TDx). When interassay and intraassay control samples were evaluated, both methods gave an overall coefficient of variation of less than +/- 10%. Using patient serum samples, we obtained excellent correlation with both methods in th...

It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic t...

OBJECTIVE To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF) and whether pulmonary deposition correlates with disease severity or genotype. METHODS A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aer...

While the MerR-like transcriptional regulator BrlR has been demonstrated to contribute to Pseudomonas aeruginosa biofilm tolerance to antimicrobial agents known as multidrug efflux pump substrates, the role of BrlR in resistance to cationic antimicrobial peptides (CAP), which is based on reduced outer membrane susceptibility, is not known. Here, we demonstrate that inactivation of brlR coincide...

The efficacy of tobramycin-containing bone cement with that of systemic cefazolin for treatment of infection in a one-stage revision model is compared. In addition, the value of detecting bacterial DNA after antibiotic treatment was investigated. An implant was inserted into the right tibia of rabbits after inoculation with Staphylococcus aureus. At 28 days, the implant was removed. Subsequentl...