Tobramycin

OBJECTIVES: Fosfomycin resistance occurs rapidly with monotherapy. This study systematically investigated bacterial killing and emergence of fosfomycin resistance with fosfomycin combinations against Pseudomonas aeruginosa.

Microbial cells embedded in a self-produced extracellular biofilm matrix cause chronic infections, e. g. by Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. The antibiotic killing of bacteria in biofilms is generally known to be reduced by 100-1000 times relative to planktonic bacteria. This makes such infections difficult to treat. We have therefore proposed that biofilms can be regarded as an independent compartment with distinct pharmacokinetics. To elucidate this pharmacokinetics we have measured the penetration of the tobramycin into seaweed alginate beads which serve as a model of the extracellular polysaccharide matrix in P. aeruginosa biofilm. We find that, rather than a normal first order saturation curve, the concentration of tobramycin in the alginate beads follows a power-law as a function of the external concentration. Further, the tobramycin is observed to be uniformly distributed throughout the volume of the alginate bead.

STUDY OBJECTIVE: To evaluate the success of an initial tobramycin dosing regimen to achieve target peak and trough concentrations in adult patients with pulmonary exacerbations of cystic fibrosis (CF).

INTRODUCTION: TOBI® Podhaler™ is a capsule-based drug-device combination (tobramycin inhalation powder [TIP] 28 mg capsules via unit-dose dry powder T-326 Inhaler [Podhaler™]) developed for treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF). We explored how inspiratory flow profiles and mouth-throat geometries affect drug delivery with the T-326 Inhaler.