Inhaled antibiotics have already been used in the treatment of other respiratory tract conditions, including cystic fibrosis (CF)67 and 68 and bronchiectasis.91 and 92 Administration of aerosolised antibiotics plays a particularly important role in CF, since patients with the condition suffer from diminished mucociliary

clearance, increasing their susceptibility to colonisation and infection by bacterial pathogens, including P. aeruginosa. 93 In this population, intermittent inhaled tobramycin has been shown to improve pulmonary function and decrease the density of P. aeruginosa in sputum, leading to significant reductions in respiratory hospitalisations. 67 and 68 Inhaled gentamycin has recently been shown to have a beneficial effect on outcomes in bronchiectasis, reducing the number of exacerbations and decreasing P. aeruginosa in the sputum. 72 In addition, use of inhaled dry powder ciprofloxacin Rapamycin cost in bronchiectasis patients has been associated with improved quality of life, which is likely to be due to reductions in bacterial load and improved eradication (of approximately

35%). 91 Inhaled antibiotics appear to be well tolerated in most of the above studies, reducing the risks Pexidartinib of adverse effects associated with systemic exposure. While wheezing and localised irritation (e.g. cough, bronchospasm) have been reported in some studies,92, 94 and 95 most report minimal side effects.67, 68 and 91 Choice of antimicrobial is dependent on pharmacokinetics/pharmacodynamics

in the bronchopulmonary tree, with the ability to achieve high Cmax values favouring concentration-killing drugs, while the applied delivery system influences particle size distribution and hence deposition and exposure. 96 and 97 Although the optimal dosing regimen (e.g. continuous or pulsed) for inhaled antibiotics in COPD has not been determined, their administration in aerosolised form has the ability to achieve high, microbiologically relevant concentrations in respiratory secretions in excess of the MIC of the infecting organism(s). 98 In COPD patients with chronic bacterial infection, delivery of a high concentration of antibiotic in Ribonucleotide reductase the airway through inhalation may lead to a reduction in chronic inflammation via a reduction in bacterial load, potentially reducing the frequency of exacerbations. Nevertheless, evidence for a reduction in airway inflammation following the use of aerosolised antibiotics is limited. The pharmacodynamic/pharmacokinetic profile of inhaled antibiotic therapy in the lower respiratory tract are quite different from systemic antibiotic use. The measured concentrations of various antibiotics (gentamycin, sisomycin, amikacin, tobramycin) in various locations in the respiratory tract following inhalation exceeded the highest MICs of the prevalent pathogens by between 50 and 125 times.