5. New Therapies
130 Antimicrobial activity of liposomal b-glycan against Pseudomonas aeruginosa isolated from cystic ﬁbrosis patients
132 Respirability assessment of amikacin from a novel dry powder inhaler versus nebulized solution
M. Halwani1 , H.H. Balkhy1 , M.A. Khiyami2 , A. Omri3 . 1 King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 2 King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia; 3 Laurentian University, Chemistry/Biochemistry, Sudbury, Canada
A.G. Balducci1,2 , F. Borella2 , R. Bettini3 , P. Colombo3 , F. Buttini3 . 1 University of Parma, Biopharmanet_TEC, Parma, Italy; 2 Plumestars srl, Parma, Italy; 3 University of Parma, Parma, Italy
Objective: Management of pseudomonal pulmonary infections associated with cystic ﬁbrosis is often difﬁcult due to the development of resistance to commonly used antibiotics. Our objective was to ﬁnd new therapeutic strategies to treat drug resistant infection by the use of liposomal formulations. Methods: The antimicrobial activity of free and liposomal b-glycan against Pseudomonas aeruginosa strains isolated from cystic ﬁbrosis patients were examined. The bacterial motility, attachment, and virulence factors in the presence of these liposomal formulations were also evaluated. The release kinetics in bronchoalveolar lavage was assessed by microbiological assay. Results: A strong antibacterial activity against most of the P. aeruginosa strains was observed in the presence of liposomal b-glycan compared to free b-glycan. Liposomal b-glycan at sub-inhibitory concentrations, attenuated the P. aeruginosa twitching swarming and swimming on agar, reduced bacterial adhesion and viability in 96-well plates and decreased protease and elastase levels. Conclusion: These liposomal b-glycan formulations could be used in the management of pulmonary infections due to Pseudomonas aeruginosa in cystic ﬁbrosis patients.
131 The experience of nebulised aztreonam lysine at the All Wales Adult CF Centre (AWACFC) A. Rees1 , R.I. Ketchell1 , C. Bridges1 , J. Duckers1 . 1 All Wales Adult Cystic Fibrosis Centre, Cardiff, United Kingdom Objectives: To evaluate the experience of patients chronically colonised with Pseudomonas aeruginosa trialled on nebulised aztreonam lysine and their outcomes over a 6 month period at the AWACFC. Methods: Patients’ FEV1 and BMI values were restrospectively collected for the 6 months pre and post aztreonam lysine and mean values were calculated. The total number of IV antibiotic days pre and post were also collected. Results: Data for 27 patients (9 males) was collected, mean (SD) age 34.0 (11.5) years range 19 to 71 years. From the 27 patients trialled 1 patient failed the trial, 1 patient discontinued, 4 patients were transplanted and 1 patient died awaiting a transplant. Objective parameter
6 months pre aztreonam lysine
FEV1 (l), mean (SD) 1.18 (0.53) No. of IV antibiotic days, mean (SD) 49.4 (20.7) BMI (kg/m2 ), mean (SD) 20.8 (2.32)
6 months post aztreonam lysine
1.19 (0.62) 37.0 (23.4) 20.9 (2.43)
0.74 0.003 0.37
Conclusion: Aztreonam lysine was well tolerated within the adult population at the AWACFC. The majority of patients commenced on aztreonam lysine generally had severe lung disease and 4 of these went on to have transplants. This is likely to account for the lack of statistical signiﬁcance for mean FEV1 and BMI change. However it is reassuring that these patients appeared stable over a 6 month period. There was a statistically signiﬁcant reduction in the number of post IV antibiotic days. The study is limited by the small number of patients included in the data and should be analysed in conjunction with a larger database.
Objectives: The aim of this work was to compare in vitro the aerodynamic behavior of an amikacin sulphate liquid solution after nebulization and an amikacin dry powder (AmikaPS) after aerosolization. AmikaPS, was prepared using a proprietary spray drying technology to construct a powder to inhale having high content of drug and respirability. Methods: Amikacin solution for injection was nebulized with Pari Turbo boy equipped with a Pari LC plus cup. AmikaPS powder was loaded in the DPI device (RS01, Plastiape) at the labeled dose of 125 mg of amikacin sulfate. Results: The dosage of amikacin solution given off-label by nebulization is 625 mg/twice a day. At the end of the nebulization, it was found that, more than 50% of the amikacin dose (625 mg amikacin sulfate corresponding to 500 mg amikacin base) remained in the ampule, about 20% was dispersed in the environment and only 17.6% of the loaded dose was delivered as aerosol available for inhalation. Thus, since the respirable fraction of this aerosol was 56.3%, the dose to lung after 625 mg nebulization resulted 61.8 mg of amikacin sulfate. The ﬁne particle dose of AmikaPS powder was 63.8 mg of amikacin sulfate. The data indicate that 125 mg of amikacin sulfate powder afford a respirable dose equivalent, or even slightly higher than that obtained by nebulizing 3 mL of solution for injection containing 625 mg of amikacin sulfate. Conclusions: The objective of the proposed amikacin product is to offer a valid alternative to the other antibiotics for inhalation, keeping as low as possible the amount of powder to be inhaled by the patient while maximizing the amount of active ingredient deposited in the lung.
133 Cost-effectiveness of dry-powder mannitol for inhalation as an add-on to best supportive care (BSC) in the treatment of adult cystic ﬁbrosis (CF) patients in Ireland M. Schwenkglenks1 , T.J. Toward2 , B. Dooley3 , R.M. Burns3 , E.J. Adams4 , J. Van Stiphout1 . 1 University of Basel, Institute of Pharmaceutical Medicine, Basel, Switzerland; 2 Pharmaxis Pharmaceuticals Ltd., Bucks, United Kingdom; 3 AXIS Healthcare Consulting Ltd, Galway, Ireland; 4 Aquarius Population Health Ltd., Bristol, United Kingdom Objectives: Despite advances in BSC, European CF patients still experience reduced life-expectancy, impaired lung function (FEV1 ) and frequent pulmonary exacerbations requiring hospital admission. Airway clearance is critical to improve outcomes but options remain limited. In pooled analysis of 2 Phase III RCTs substantiating the EU adult license, inhaled dry-powder mannitol (Bronchitol® ) improved FEV1 (p < 0.001) and reduced pulmonary exacerbations (ns). Ireland has the highest rate of CF worldwide. A cost-utility analysis was undertaken to assess the clinical, quality adjusted life year (QALY) and economic impact of mannitol use in Ireland. Methods: A decision-analytic microsimulation framework assessed the incremental cost-effectiveness ratio (ICER) of BSC plus mannitol versus BSC alone. A life-long time horizon from the perspective of the publicly-funded Health Service Executive (HSE) was adopted. Model inputs included RCT, expert opinion, local unit-cost and tabulated anonymised CF Registry data. Results: Compared to BSC alone, simulated patients receiving BSC plus mannitol had a lower estimated exacerbation rate, lived longer and gained 0.54 QALYs. The resulting ICER was €33,772 per QALY gained. Additional net costs (€18,370) were driven by drugs and prolonged life. Lung transplant costs were 5% lower. The ICER was relatively robust in deterministic sensitivity analysis with most variation from assumptions on the impact of mannitol on exacerbations. In probabilistic analysis, 74% of ICERs were below a €45,000 willingness to pay threshold. Conclusion: In adults with CF, mannitol added to BSC is clinically beneﬁcial and a cost-effective option for the HSE in Ireland.