67, 91, 106, 107, 108, 109, 110, 111, 112, 113, 114, Selleck Ku-0059436 115 and 116 However, adequate delivery of antibiotic to the airways through inhalation is a complex method influenced by several factors. Conditions that have to be optimised include the choice of nebuliser (jet
or ultrasonic, vibrating mesh inhaler), the drug formulation (aerosolised solution or dry powder), the particle size (must be between 1 μm and 5 μm for adequate deposition and delivery into lower airways), the chemical properties of the molecule (e.g. lipophilic or hydrophilic). Furthermore, patient characteristics including age and lung function, the respiratory cycle length and inspiratory/expiratory ratio, may also influence efficiency of inhaled antibiotic delivery. As seen with long-term systemic antibiotic use, selleck concern exists too for inhaled antibiotics regarding the possibility of resistance development during long-term treatment. As shown in Table 3, there is inconsistent evidence for the emergence of resistant pathogens during treatment with aerosolised antibiotics
in some respiratory conditions67 and 95 (Table 3). It is likely that risk of resistance development may be lessened by use of shorter courses, intermittent therapy (as currently practiced in cystic fibrosis) or alternating different antibiotic classes. To date, there have been only two published reports investigating the use of inhaled antibiotics in patients with Rebamipide COPD. Dal Negro et al.117 examined the impacts of 14-day, twice daily treatment with inhaled tobramycin nebuliser solution on clinical outcome as well as inflammatory markers in bronchial secretions from a small cohort (n = 13) of multiresistant P. aeruginosa-colonised patients with severe COPD (FEV1 < 50% predicted). P. aeruginosa infection is associated with a severe degree of functional impairment in COPD, 118 and colonisation could well herald the presence of bronchiectasis, 41 and 119 suggesting a potential role for inhaled antibiotics. Indeed, such treatment resulted in a substantial reduction from baseline
of pro-inflammatory chemotactic mediators, including interleukin-1 beta (P < 0.03), interleukin-8 (P < 0.02) and eosinophilic cationic protein (P < 0.01). After the 6-month follow-up period, P. aeruginosa was considered to be eradicated in two patients, while P. aeruginosa density was reduced in a further four patients. Two-week treatment with inhaled tobramycin decreased the frequency of exacerbations by 42%, when compared with the 6-month period prior to initiating inhaled tobramycin therapy. 117 Although this study has many limitations, including its open-label design and its small size, it does suggest a therapeutic role for inhaled antibiotics in COPD patients, particularly those colonised with multiresistant P. aeruginosa.
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