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ePS06.6 Antimicrobial activity of a novel liposomal azithromycin formulation against clinical CF respiratory isolates
Oral Presentations / Journal of Cystic Fibrosis 15 (2016) S1–S50
as efficient as the PARI-LC. The OD dosing regimen increased these concentrations even further. Acknowledgement: Supported by unrestricted grant by Chiesi Farmaceutici S.p.A. ePS06.5 Post-hoc review of outcomes in patients switching from tobramycin for nebulization solution (TNS) to aztreonam lysine for inhalation (AZLI) M. Fayon1 , C.M. Oermann2 , T. Pressler3 , J. Wicklund4 , J. Brekke4 , H. Liu4 , M. Bresnik4 , B. Assael5 . 1 Hˆ opital Pellegrin-Enfants CHU de Bordeaux, Bordeaux, France; 2 Children’s Mercy Hospitals and Clinics, Kansas City, United States; 3 National University Hospital, Copenhagen, Denmark; 4 Gilead Sciences, Foster City, United States; 5 Centro Fibrosi Cistica, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy Objectives: The AZLI vs. TNS Active Comparator study evaluated the effect of 3 on-off courses of AZLI (28-days TID) compared to TNS (28-days BID) in chronic Pseudomonas aeruginosa infected CF patients (pts). A post-hoc analysis was conducted to explore the impact of switching from TNS to AZLI in pts taking TNS prior to being randomized to AZLI, and in pts randomized to TNS and then switched to AZLI in the extension phase of the study. Methods: Group 1 pts were those who reported >84 days of TNS use in the 12 months prior to randomization in the Active Comparator study. Group 2 pts were those initially randomized to TNS and then switched to AZLI in the extension phase. The mean change over 3 treatment cycles in FEV1 , CFQ-R Respiratory Symptoms Score (RSS), and body weight in Group 1 were compared to baseline values. Mean changes in these values observed in Group 2 over 3 cycles of AZLI during the extension phase were compared to the 3 cycles on TNS during the active comparator phase of the study. Results: The 114 pts in Group 1 demonstrated significant improvements in mean FEV1 (3.3% predicted; p < 0.0.05), CFQ-R RSS (4.93; p < 0.05) and weight (0.40 kg; p < 0.05). The 65 pts in Group 2 demonstrated significantly improvements in mean FEV1 (1.55% predicted; p < 0.05), CFQ-R RSS (2.84; p < 0.05) and weight (0.47 kg; p < 0.05). Conclusion: Significant improvements in lung function, patientreported symptoms and body weight were observed in both TNS to AZLI groups suggesting that patients may benefit from a switch in inhaled antibiotic treatment. Acknowledgement: Supported by Gilead Sciences ePS06.6 Antimicrobial activity of a novel liposomal azithromycin formulation against clinical CF respiratory isolates Y.D. Bashi1 , J. Payne2 , S.J. McGrath1 , J.S. Elborn2 , M.M. Tunney1 , V.L. Kett1 . 1 Queen’s University Belfast, Pharmacy, Belfast, United Kingdom; 2 Queens University Belfast, Centre for Infection and Immunity, Belfast, United Kingdom Objectives: Oral azithromycin maintenance therapy is frequently prescribed in CF as it has been shown to improve long-term clinical outcome. However, systemic azithromycin use is associated with toxic effects. Entrapment of antimicrobial agents in liposomes has the potential to enable direct delivery to the site of infection in the lungs and to reduce toxic side-effects. Therefore, this study aimed to determine the antimicrobial activity of a novel liposomal azithromycin formulation against clinical respiratory isolates. Methods: Antimicrobial activity of free azithromycin and azithromycin loaded liposomes against clinical P. aeruginosa and S. aureus isolates was determined using minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC), time-kill and biofilm assays. Liposomal uptake by isolates was determined using flow cytometry analysis. Results: In general, there was no difference in MIC/MBC values for free and liposomal loaded azithromycin. The majority of P. aeruginosa and S. aureus isolates were resistant with MBCs ranging from 128 to >256 mg/ml and 8 to >256 mg/ml, respectively. However, liposomal azithromycin was significantly more potent than free azithromycin in both prevention of P. aeruginosa biofilm formation and eradication of
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P. aeruginosa biofilms. Liposomal uptake ranged from 57% to 96% for P. aeruginosa and from 58% to 78% for S. aureus. Conclusion: This novel liposomal azithromycin formulation could be potentially useful in the management of CF respiratory infection. Acknowledgement: Work part funded by a US-Ireland Project Partnership Grant (HSC R&D, Public Health Agency, NI). ePS06.7 Antibiotic treatment strategy with fusidic acid on colistin resistant Pseudomonas aeruginosa in cystic fibrosis H. Wang1,2 , F. Li1 , O. Ciofu2 , N. Høiby1,2 . 1 Rigshospitalet, University Hospital of Copenhagen, Department of Clinical Microbiology, Copenhagen, Denmark; 2 University of Copenhagen, Faculty Of Health and Medical Sciences, Department of Immunology and Microbiology, Copenhagen, Denmark Colistin resistant P. aeruginosa is a challenging problem in the treatment of chronic lung infection of cystic fibrosis (CF). Combination antimicrobial treatment is a strategy to reduce the emergence of bacterial resistance. Recent studies were to investigate the effect of fusidic acid in colistin resistant P. aeruginosa in vitro. Clinical resistant strains from CF lung with PhoQ and PmrB mutations were involved in this study. MICs of colistin and fusidic acid for these planktonic strains were tested by E-test and microdilution method. The combination effect of colistin/fusidic acid was detected by microdilution method and disk diffusion method. Time-kill method was used to check the killing effect of colistin and fusidic acid. A screening test for potential synergy between colistin and fusidic acid was performed by checkerboard method. MICs of colistin to these PhoQ and PmrB mutants of P. aeruginosa were 16 mg/l to >512 mg/l, and 256 to >2048 for fusidic acid. MICs of colistin/fusidic acid combination were 4 mg/l to 32 mg/l with 4–32 times decrease on these colistin resistant strains of P. aeruginosa. Synergistic effect of colistin/fusidic acid combination was found in disk diffusion test and checkerboard test on all these colistin resistant mutants. Time-kill assays showed that bactericidal killing in colistin/fusidic acid combination was superior to colistin alone. Results with colistin/fusidic acid combinations showed a synergistic effect in planktonic colistin resistant strains of P. aeruginosa with PhoQ and PmrB mutations. Combination antibiotic therapy of colistin/fusidic acid may be a candidate strategy for the treatment of colistin resistant strains in the CF lung. ePS06.8 Fungal disease and triazole treatment in adults with cystic fibrosis, 2012–2014: treatment trends, clinical characteristics and safety L. Spurr1 , E. Bowman1 , A.M. Jones1 , S. Schelenz1 , D. Armstrong-James1 , N.J. Simmonds1 . 1 Royal Brompton Hospital, London, United Kingdom Objectives: To describe prescribing practice of the 3 currently available azoles, compare clinical characteristics and outline their safety. Methods: From the UK-Patient Registry, we obtained cross-sectional data of all (exc. transplanted) patients in our adult CF centre that received azoles (itraconazole (itra); voriconazole (vori); posaconazole (posa)) each year from 2012–2014. Additional data was collected from electronic medical records. Clinical characteristics of the 2014 cohort on azoles (n = 104) were compared to non-azole treated patients (n = 473). Effectiveness and safety were reviewed in a sub-group (2014 cohort), chosen at random [n = 10 (itra), 10 (vori), 10 (posa)]. Results: Azole usage increased proportionately each year [11.5% (n = 65) 2012; 15.1% (n = 90) 2013; 18.1% (n = 104) 2014] which was mostly driven by vori (2012, 21.5% (n = 14) to 2014, 26.9% (n = 28)]. Comparatively azole patients had significantly (p < 0.001) lower median BMI (21 vs 23) and FEV1% (55% vs 64%) and more CFRD (48% vs 26%) and median days on IV antibiotics (15 vs 0). 79% of all azole patients had Aspergillusrelated disease. Of the 2014 sub-group (n = 30), median treatment duration (months): itra 7.5 (2–20); vori 20.7 (4–29); posa 22.5 (1–47). 70% (n = 7) on vori had switched from itra (57% sub-therapeutic; 43% lack of efficacy). 70% (n = 7) on posa had switched to vori from itra (43% nonadherent; 29% lack of efficacy; 14% sub-therapeutic; 14% failed trial off itra) then to posa (86% side effects; 14% sub-therapeutic). No discontinuations occurred on posa.
as efficient as the PARI-LC. The OD dosing regimen increased these concentrations even further. Acknowledgement: Supported by unrestricted grant by Chiesi Farmaceutici S.p.A. ePS06.5 Post-hoc review of outcomes in patients switching from tobramycin for nebulization solution (TNS) to aztreonam lysine for inhalation (AZLI) M. Fayon1 , C.M. Oermann2 , T. Pressler3 , J. Wicklund4 , J. Brekke4 , H. Liu4 , M. Bresnik4 , B. Assael5 . 1 Hˆ opital Pellegrin-Enfants CHU de Bordeaux, Bordeaux, France; 2 Children’s Mercy Hospitals and Clinics, Kansas City, United States; 3 National University Hospital, Copenhagen, Denmark; 4 Gilead Sciences, Foster City, United States; 5 Centro Fibrosi Cistica, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy Objectives: The AZLI vs. TNS Active Comparator study evaluated the effect of 3 on-off courses of AZLI (28-days TID) compared to TNS (28-days BID) in chronic Pseudomonas aeruginosa infected CF patients (pts). A post-hoc analysis was conducted to explore the impact of switching from TNS to AZLI in pts taking TNS prior to being randomized to AZLI, and in pts randomized to TNS and then switched to AZLI in the extension phase of the study. Methods: Group 1 pts were those who reported >84 days of TNS use in the 12 months prior to randomization in the Active Comparator study. Group 2 pts were those initially randomized to TNS and then switched to AZLI in the extension phase. The mean change over 3 treatment cycles in FEV1 , CFQ-R Respiratory Symptoms Score (RSS), and body weight in Group 1 were compared to baseline values. Mean changes in these values observed in Group 2 over 3 cycles of AZLI during the extension phase were compared to the 3 cycles on TNS during the active comparator phase of the study. Results: The 114 pts in Group 1 demonstrated significant improvements in mean FEV1 (3.3% predicted; p < 0.0.05), CFQ-R RSS (4.93; p < 0.05) and weight (0.40 kg; p < 0.05). The 65 pts in Group 2 demonstrated significantly improvements in mean FEV1 (1.55% predicted; p < 0.05), CFQ-R RSS (2.84; p < 0.05) and weight (0.47 kg; p < 0.05). Conclusion: Significant improvements in lung function, patientreported symptoms and body weight were observed in both TNS to AZLI groups suggesting that patients may benefit from a switch in inhaled antibiotic treatment. Acknowledgement: Supported by Gilead Sciences ePS06.6 Antimicrobial activity of a novel liposomal azithromycin formulation against clinical CF respiratory isolates Y.D. Bashi1 , J. Payne2 , S.J. McGrath1 , J.S. Elborn2 , M.M. Tunney1 , V.L. Kett1 . 1 Queen’s University Belfast, Pharmacy, Belfast, United Kingdom; 2 Queens University Belfast, Centre for Infection and Immunity, Belfast, United Kingdom Objectives: Oral azithromycin maintenance therapy is frequently prescribed in CF as it has been shown to improve long-term clinical outcome. However, systemic azithromycin use is associated with toxic effects. Entrapment of antimicrobial agents in liposomes has the potential to enable direct delivery to the site of infection in the lungs and to reduce toxic side-effects. Therefore, this study aimed to determine the antimicrobial activity of a novel liposomal azithromycin formulation against clinical respiratory isolates. Methods: Antimicrobial activity of free azithromycin and azithromycin loaded liposomes against clinical P. aeruginosa and S. aureus isolates was determined using minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC), time-kill and biofilm assays. Liposomal uptake by isolates was determined using flow cytometry analysis. Results: In general, there was no difference in MIC/MBC values for free and liposomal loaded azithromycin. The majority of P. aeruginosa and S. aureus isolates were resistant with MBCs ranging from 128 to >256 mg/ml and 8 to >256 mg/ml, respectively. However, liposomal azithromycin was significantly more potent than free azithromycin in both prevention of P. aeruginosa biofilm formation and eradication of
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P. aeruginosa biofilms. Liposomal uptake ranged from 57% to 96% for P. aeruginosa and from 58% to 78% for S. aureus. Conclusion: This novel liposomal azithromycin formulation could be potentially useful in the management of CF respiratory infection. Acknowledgement: Work part funded by a US-Ireland Project Partnership Grant (HSC R&D, Public Health Agency, NI). ePS06.7 Antibiotic treatment strategy with fusidic acid on colistin resistant Pseudomonas aeruginosa in cystic fibrosis H. Wang1,2 , F. Li1 , O. Ciofu2 , N. Høiby1,2 . 1 Rigshospitalet, University Hospital of Copenhagen, Department of Clinical Microbiology, Copenhagen, Denmark; 2 University of Copenhagen, Faculty Of Health and Medical Sciences, Department of Immunology and Microbiology, Copenhagen, Denmark Colistin resistant P. aeruginosa is a challenging problem in the treatment of chronic lung infection of cystic fibrosis (CF). Combination antimicrobial treatment is a strategy to reduce the emergence of bacterial resistance. Recent studies were to investigate the effect of fusidic acid in colistin resistant P. aeruginosa in vitro. Clinical resistant strains from CF lung with PhoQ and PmrB mutations were involved in this study. MICs of colistin and fusidic acid for these planktonic strains were tested by E-test and microdilution method. The combination effect of colistin/fusidic acid was detected by microdilution method and disk diffusion method. Time-kill method was used to check the killing effect of colistin and fusidic acid. A screening test for potential synergy between colistin and fusidic acid was performed by checkerboard method. MICs of colistin to these PhoQ and PmrB mutants of P. aeruginosa were 16 mg/l to >512 mg/l, and 256 to >2048 for fusidic acid. MICs of colistin/fusidic acid combination were 4 mg/l to 32 mg/l with 4–32 times decrease on these colistin resistant strains of P. aeruginosa. Synergistic effect of colistin/fusidic acid combination was found in disk diffusion test and checkerboard test on all these colistin resistant mutants. Time-kill assays showed that bactericidal killing in colistin/fusidic acid combination was superior to colistin alone. Results with colistin/fusidic acid combinations showed a synergistic effect in planktonic colistin resistant strains of P. aeruginosa with PhoQ and PmrB mutations. Combination antibiotic therapy of colistin/fusidic acid may be a candidate strategy for the treatment of colistin resistant strains in the CF lung. ePS06.8 Fungal disease and triazole treatment in adults with cystic fibrosis, 2012–2014: treatment trends, clinical characteristics and safety L. Spurr1 , E. Bowman1 , A.M. Jones1 , S. Schelenz1 , D. Armstrong-James1 , N.J. Simmonds1 . 1 Royal Brompton Hospital, London, United Kingdom Objectives: To describe prescribing practice of the 3 currently available azoles, compare clinical characteristics and outline their safety. Methods: From the UK-Patient Registry, we obtained cross-sectional data of all (exc. transplanted) patients in our adult CF centre that received azoles (itraconazole (itra); voriconazole (vori); posaconazole (posa)) each year from 2012–2014. Additional data was collected from electronic medical records. Clinical characteristics of the 2014 cohort on azoles (n = 104) were compared to non-azole treated patients (n = 473). Effectiveness and safety were reviewed in a sub-group (2014 cohort), chosen at random [n = 10 (itra), 10 (vori), 10 (posa)]. Results: Azole usage increased proportionately each year [11.5% (n = 65) 2012; 15.1% (n = 90) 2013; 18.1% (n = 104) 2014] which was mostly driven by vori (2012, 21.5% (n = 14) to 2014, 26.9% (n = 28)]. Comparatively azole patients had significantly (p < 0.001) lower median BMI (21 vs 23) and FEV1% (55% vs 64%) and more CFRD (48% vs 26%) and median days on IV antibiotics (15 vs 0). 79% of all azole patients had Aspergillusrelated disease. Of the 2014 sub-group (n = 30), median treatment duration (months): itra 7.5 (2–20); vori 20.7 (4–29); posa 22.5 (1–47). 70% (n = 7) on vori had switched from itra (57% sub-therapeutic; 43% lack of efficacy). 70% (n = 7) on posa had switched to vori from itra (43% nonadherent; 29% lack of efficacy; 14% sub-therapeutic; 14% failed trial off itra) then to posa (86% side effects; 14% sub-therapeutic). No discontinuations occurred on posa.