Microbiological Progress in Patients with Bronchial Infection with Pseudomonas aeruginosa Treated with Nebulised Colistin.

BACKGROUND: Inhaled antibiotics allow the delivery of higher drug concentrations at the site of infection without the systemic adverse effects observed with the use of parenteral or oral antibiotics. These antibiotics have shown to decrease the number of exacerbations, reduce bacterial load or improve pulmonary function in several chronic respiratory conditions. OBJECTIVES: The aim of this study was to describe changes in the bacteriology of sputum in patients with chronic bronchial infection with Pseudomonas aeruginosa treated with nebulised colistin. MATERIAL AND METHODS: All patients with chronical infection with P. aeruginosa treated with nebulised colistin attending a day care unit during a 5-year (January 2010 to December 2014) period were included. Repeated-measures t tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalisations. RESULTS: Treatment with colistin was associated with a decrease in the number of ambulatory exacerbations (1.87-1.1, p = 0.007), of hospital exacerbations (1.3-0.7, p = 0.010) and of length of stay (15.7-8.6 days, p = 0.005). There was no linear trend in the proportion of isolate Enterobacteriaceae, gram-positive cocci, Haemophilus influenzae or fungi. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulised colistin was associated with an increase in the number of ambulatory exacerbations (incidence rate ratio 1.99, 95% CI 1.05-3.79). CONCLUSIONS: Nebulised colistin was effective in the treatment of chronic infection with P. aeruginosa, and no significant changes in the microbiological evolution were observed. Isolation of Enterobacteriaceae within 1 year after the beginning of the treatment with nebulised colistin was associated with an increase in the number of exacerbations.

A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models.

BACKGROUND: Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic. METHODS: In vitro studies using a laser diffractometer and a bacterial-viral filter were used to measure the effect of the type and size of tracheal tubes and antibiotic concentration on the particle size distribution of the tobramycin 400 mg (4 ml; 100 mg/ml) and 160 mg (4 ml, 40 mg/ml) aerosol and nebulised mass delivered. To compare the regional drug distribution in the lung of two routes (intravenous and nebulised) of drug administration of tobramycin 400 mg, technetium-99m-labelled tobramycin 400 mg with planar nuclear medicine imaging was used in a mechanically ventilated ovine model. To measure tobramycin concentrations by intravenous and nebulised tobramycin 400 mg (4 ml, 100 mg/ml) administration in the lung interstitial space (ISF) fluid and blood of mechanically ventilated sheep, the microdialysis technique was used over an 8-h duration. RESULTS: Tobramycin 100 mg/ml achieved a higher lung dose (121.3 mg) compared to 40 mg/ml (41.3 mg) solution. The imaging study with labelled tobramycin indicated that nebulised tobramycin distributed more extensively into each lung zone of the mechanically ventilated sheep than intravenous administration. A higher lung ISF peak concentration of tobramycin was observed with nebulised tobramycin (40.8 mg/l) compared to intravenous route (19.0 mg/l). CONCLUSIONS: The research methods appear promising to describe lung pharmacokinetics for formulations intended for nebulisation during mechanical ventilation. These methods need further validation in an experimental pneumonia model to be able to contribute toward optimising dosing regimens to inform clinical trials and/or clinical use.

Long-term antibiotic treatment for non-cystic fibrosis bronchiectasis in adults: evidence, current practice and future use.

INTRODUCTION: Bronchiectasis is defined pathologically by the permanent dilation of the bronchi and bronchioles and chronic airway inflammation. This is the outcome of a number of different aetiologies but up to half of bronchiectasis cases are labelled idiopathic. It is characterised by a chronic productive cough, haemoptysis, shortness of breath and recurrent infective exacerbations. Long-term antibiotics are used with the aim of reducing symptom severity and exacerbation frequency, improving quality of life and preventing disease progression. Areas covered: This perspective provides an overview of evidence and current practice for long-term oral, inhaled and pulsed intravenous antibiotic therapy in adults with non-cystic fibrosis bronchiectasis. Evidence was drawn from a recent systemic literature review. Expert commentary: An approach to long-term antibiotic treatment is provided. Side effects of treatment, methods of monitoring treatment success and actions to be considered if treatment fails are discussed. Emerging long-term antibiotic treatments and strategies are considered.

Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review.

We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled ß-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.