- Email: [email protected]
Survival of the PAH and CTEPH Patients in the Swedish Pulmonary Arterial Hypertension Register 2000-2014
Abstracts S361 1( 005) Right Ventricular Performance with Exercise Declines Predictably in Patients with Idiopathic PAH P. Jain , A. Jabbour, E. Kotlyar, C. Hayward, P. Macdonald, A. Keogh. Cardiology, St Vincent’s Hospital, Sydney, Australia. Purpose: Understanding the response of the right ventricle to exercise in pulmonary arterial hypertension (PAH) is critical to improved overall understanding of exercise haemodynamics, which may facilitate early diagnosis and improve prognostication. We sought to characterise this response in patients with established PAH of varying severity and aetiology. Methods: Patients with PAH due to idiopathic disease, scleroderma or chronic thromboembolic pulmonary hypertension (CTEPH) now routinely undergo rest and exercise right heart catheterisation in one sitting in our unit using either supine cycle ergometer or straight leg raise. Standard measurements performed include cardiac output by the thermodilution method. Results: We analysed data from 53 right heart catheterisations (idiopathic = 28, scleroderma = 16, CTEPH = 9). There were no differences between aetiologies in terms of WHO functional class (median = 3 for all groups). Patients with idiopathic disease had a significantly higher resting mPAP but proportionally smaller increase with exercise compared to those with scleroderma and CTEPH. Right ventricular stroke work index (RVSWI) was higher at baseline in patients with idiopathic disease, with reduced exercise-induced augmentation (figure 1). There was a negative, non-linear correlation (r2 = 0.60) between RVSWI augmentation with exercise and baseline mPAP (figure 2) which did not exist in patients with scleroderma and CTEPH (r2= 0.23). Conclusion: Patients with idiopathic PAH demonstrate an early, predictable decline in right ventricular performance with exercise that is not seen in PAH due to scleroderma or CTEPH.
1( 006) Change in PH Therapy from PDE5i to Riociguat Is Associated with Significant Incremental Increase in Cardiac Index, Decrease in Pulmonary Vascular Resistance and Mean Arterial Pressure R.A. Davey , A. Raina, G. Sokos, M. Kanwar, M. Patarroyo Aponte, R. Agarwal, R.L. Benza. Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA. Purpose: Pulmonary hypertension (PH) is characterized by vascular remodeling and progressive constriction. Phosphodiesterase-5 inhibitors (PDE5i) are a well studied class of pulmonary vasodilators. Recently, a soluble
guanylate cyclase stimulator, riociguat, has also been used in place of PDE5i but the benefit of switching from PDE5 to this drug has not been established. We sought to investigate the clinical and hemodynamic effects of replacing PDE5i with riociguat. Methods: We retrospectively analyzed data from patients who had been switched from a PDE5i to riociguat for a clinical indication. Baseline (prePDE5i), on PDE-5i, and post-riociguat exchange hemodynamic and clinical data were analyzed to determine if any changes were associated with riociguat exchange. Covariate analysis was performed to correct for length of time on therapy and whether other PH specific therapies had been added or intensified. Results: 18 consecutive PDE5i to riociguat switch patients were screened for inclusion and, since 5 were found to have incomplete records, 13 were included for analysis. In comparing pre-PDE5i to post-PDE5i parameters, there were no significant hemodynamic or clinical differences between the groups after a mean of 172 weeks of follow-up despite 75% of patients having other PH therapies added or intensified. However, after PDE5i to riociguat exchange for a minimum of 12 weeks (mean 34 weeks), cardiac index (CI) by Fick increased by 0.41±0.16 L/min/m2 (p= 0.026), pulmonary vascular resistance (PVR) decreased by 1.56±0.67 WU (p= 0.037) and mean arterial pressure (MAP) decreased by 19±5 mmHg (p= 0.001). Further, covariate analysis showed no significant contribution from length of time on riociguat or whether PH therapies were intensified at the time of riociguat exchange. Conclusion: We conclude that PDE5i to riociguat exchange is a viable option for patients with worsening clinical status and, after 12 weeks, is associated with significantly increased CI, decreased PVR, and decreased MAP irrespective of intensifying other PH directed therapies or extended use of the drug beyond 12 weeks. Forthcoming data from the prospective RESPITE trial may aid in further delineating this relationship. 1( 007) Survival of the PAH and CTEPH Patients in the Swedish Pulmonary Arterial Hypertension Register 2000-2014 G. Rådegran ,1 B. Kjellström,2 B. Ekmehag,3 R. Hesselstrand,4 B. Kornhall,1 F. Larsen,5 M. Nissel,6 B. Rundkvist,7 B. Ullman,8 K. Wall,9 G. Wikström,10 M. Willehadson,10 K. Jansson,11 S. Söderberg.12 1Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden; 2Cardiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden; 3Department of Public Health and Caring Science, Uppsala University, Uppsala, Sweden; 4Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden; 5Department of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institute, Stockholm, Sweden; 6Department of Medicine, Karolinska Institute, Stockholm, Sweden; 7Department of Cardiology, The Sahlgenska Academy, Gothenburg University, Gothenburg, Sweden; 8Department of Cardiology, Karolinska Institute, Stockholm, Sweden; 9Department of Clinical Physiology, Örebro University, Örebro, Sweden; 10Department of Medical Sciences Cardiology, Uppsala University, Uppsala, Sweden; 11Departments of Cardiology and Clinical Physiology, Institution of Medicine and Health Sciences, Linköping University, Linköping, Sweden; 12Department of Public Health and Clinical Medicine, Cardiology and the Heart Centre, Umeå University, Umeå, Sweden. Purpose: To define characteristics and survival of the pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients in Sweden. Methods: Incident and prevalent cases of PAH and CTEPH patients included in the Swedish Pulmonary Arterial Hypertension Register (SPAHR) between 2000 and 2014 were reviewed. Results: SPAHR included 697 PAH patients, whereof 392 were alive at the end of 2014. Median age at diagnosis was 63 years (66% female), whereof 80% were in functional-class-III-IV. Corresponding numbers for CTEPH were 247 patients, whereof 153 were alive at the end of 2014. Median age at diagnosis was 68 years (49% female), whereof 82% in functional-class-III-IV. In 2014 the prevalence of IPAH/HPAH, APAH and CTEPH were 25, 24 and 19 and the incidence 5, 2 and 3, per million inhabitants, respectively. One, three and five year survival was 78, 65 and 53% for PAH and 85, 77 and 71% for CTEPH. In the univariate analyses (Hazard ratio [95% Confidence Intervals]),
S362
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
APAH-others and APAH-CHD had a better survival compared to IPAH/ HPAH (0.35 [0.14-0.85] and 0.44 [0.25-0.78], respectively), whereas APAH-CTD had a worse survival compared to IPAH-HPAH (1.42 [1.041.92]). The differences were attenuated after adjustments for age and sex, but remained for APAH-CTD compared to IPAH-HPAH (0.60 [0.241.50], 0.74 [0.41-1.33], and (1.41 [1.03-1.94], respectively). CTEPH patients who had undergone pulmonary endarterectomy (PEA) had better survival compared to those without PEA (0.29 [0.13-0.64]), although attenuated after adjustments for age and sex (0.43 [0.18-1.02]). Survival for patients diagnosed 2005-2009 or 2010-2014 did not differ (p= 0.56), however, survival appeared worse (p< 0.01, for both) compared to those diagnosed 2000-2004. The difference between the two later compared to the first period did not remain (p greater than 0.80, for both) after adjustment for sex and age. Conclusion: The majority of PAH and CTEPH patients in Sweden were in functional-class-III-IV and 60-79 years old at diagnosis. Survival in our PAH cohort has improved compared to historical data of untreated PAH patients in the US NIH registry, and differs between PH-subgroups, but the analysis also indicates a survival bias related to prevalent vs. incident cases, comparing the time period of 2000-2004 with 2005-2009 respectively 2010-2014. 1( 008) Autologous Transfusion of Stored Red Blood Cells Impairs Endothelium-Dependent Vasodilatation in Experimental Pulmonary Arterial Hypertension. This Effect Is Reversed by Inhaled Nitric Oxide A. Rungatscher ,1 L. Daniele,1 L. San Biagio,1 S. Bombieri,1 S. Hallström,2 G. Luciani,1 G. Faggian.1 1University f Verona, Verona, Italy; 2Institute of Physiological Chemistry, University of Graz Medical School, Graz, Austria. Purpose: Transfusion with erythrocytes stored for prolonged periods increases plasma free hemoglobin (fHb), which scavenges endogenous nitric oxide (NO). The present study aimed to investigate the effects of autologous transfusion of stored erythrocytes with or without contemporary nitric oxide administered by inhalation (iNO) in a model of pulmonary arterial hypertension (PAH). Methods: PAH was induced in 30 male Wistar rats exposed to left to right shunt (Qp/Qs > 2). After 10 weeks they were randomly treated with saline (control) or with autologous erythrocytes stored for 20 days (5 ml/h) with or without iNO (30 ppm for 60 min). fHb and NO consumption was determined in plasma. Right ventricular (RV) contractility and ventricular-vascular coupling were assessed in vivo at different pre-loads by conductance catheter. Endotheliumdependent relaxation was assessed in vitro in pulmonary artery rings. Results: Results: Rats treaded with stored erythrocytes had significantly higher fHb plasma concentrations, which correlated with NO consumption (r = 0.75, p < 0.01). RV afterload expressed by effective pulmonary arterial elastance was higher in transfused rats but not in the group receiving contemporary iNO compared to control (Ea; 1.3 ± 0.5 vs 0.5 ± 0.3 vs. 0.6 ± 0.5 mm Hg/ml, respectively; p < 0.001). Ventricular-vascular coupling (Ees/Ea) was impaired after transfusion and this effect was completely abolished by iNO. Maximal endothelium-dependent relaxation in pulmonary artery was significantly attenuated in rats receiving transfusion but not in those receiving contemporary iNOS nor in the control (13.2 ± 1.5 vs. 38.5 ± 2.3 vs. 40.5 ± 2.0 %, respectively; p < 0.001). Conclusion: Transfusion with autologous stored erythrocytes worsens pulmonary arterial hypertension impairing endothelium dependent relaxation through NO scavenging by fHb. iNO completely abolish this phenomenon. 1( 009) WITHDRAWN 1( 010) Antimicrobial Activity of Cysteamine Against Antibiotic Resistant Pathogens Isolated from Cystic Fibrosis and Non- CF Patients Including Mycobacterium abscessus Complex from Lung Transplant Recipients A. Perry , J.D. Perry, C. Preece, D. Tierney, S. Peart, F.K. Gould. Microbiology Department, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Purpose: Lung transplantation for cystic fibrosis (CF) patients colonised with pan resistant bacteria, in particular M abscessus complex (MABSC) may preclude them from lung transplantation due to poor outcomes. Treatment of MABSC generally consists of a 3 drug regime including nephrotoxic/ototoxic amikacin. Oral cysteamine is licenced for treatment of cystinosis and has recently been reported as having good antimicrobial, anti-biofilm and mucolytic activity against CF pathogens. We evaluated the antimicrobial activity of this compound against a collection of 31 strains of CF and non- CF pathogens including isolates from lung transplant recipients. We also evaluated the interaction of cysteamine with 12 anti-pseudomonal agents against 4 strains P aeruginosa (Pa). Methods: Microdilution MIC’s against 12 MABSC were performed and bactericidal activity was assessed by subculture. MIC’s were performed against a collection of 19 further strains including: Pa (n= 3), Achromobacter spp. (n= 2) and 1 each of the following: Burkholderia multivorans, Burkholderia cenocepacia, Ralstonia mannitolylitica, Pandoraea sp. Stenotrophomonas maltophilia, and Inquilinus limosus. NCTC strains of E coli, S aureus; C albicans, E faecalis and 4 carbapenemase-producing Enterobacteriacae (CPE) were also evaluated. The Multiple Combination Bactericidal Test (MCBT) was utilised to assess synergy by incorporating cysteamine at 500 mg/L with 12 agents at the systemic concentration. The 4 strains selected were only susceptible to colomycin. Results: Cysteamine at 500 mg/L was bactericidal against all 4 strains of Pa and no antagonism was observed with antipseudomonal agents. The MIC’s of 12 MABSC were 256-1024 mg/L with bactericidal activity against 9 strains at 1024 mg/L and 512 mg/L for 2 strains. One strain was inhibited at 256 mg/L but no bactericidal activity observed at 1024 mg/L. The MIC’s of the 19 other isolates ranged from 64-1024 mg/L with bactericidal activity ranging from 128-1024 mg/L for all except C albicans. Conclusion: The results of this study demonstrate that cysteamine has potential as an antimicrobial for the treatment of severe infection caused by pan resistant bacteria in lung transplant patients with or without CF and warrants further evaluation. 1( 011) Posaconazole Tablets Exposure in the Real-Life of Lung Transplantation B. Douvry ,1 B. Toussaint,2 A. Roux,1 L. Lecuyer,3 E. Rivaud,1 L. Couderc,1 V. Boussaud,3 D. Grenet,1 R. Guillemain,3 E.M. Billaud.2 1Pneumology, Hosp Foch, Suresnes, France; 2Pharmacology, Hosp Georges Pompidou, Paris Cedex 15, France; 3Thoracic Transplantation, Hosp Georges Pompidou, Paris Cedex 15, France. Purpose: Appropriate exposure to Posaconazole (PSZ) was limited since the recent approval of the delayed release oral tablet formulation. Our goal is to determine the exposure obtained using the standard dose of 300 mgx1 in lung transplant patients (LT) including cystic fibrosis (CF) background. Methods: We prospectively included all patients receiving PSZ tablet 300 mgx1 under Therapeutic Drug Monitoring (TDM) evaluation performed in our centre. PSZ trough plasma concentrations (C0) were determined using LCMS assay. Indicative thresholds of interest were based on the usual < 0.5 mg/L (prophylaxis) and 0.7 mg/L (curative). Results: During June-October 2015 period, we recorded 9 LT and 12 non LT patients (P) addressed to Pneumology department from 2 centres among a multicentre cohort of over 60 patients. Respectively in LT vs P: demographics were 37.7±18.7 vs 56±17 yrs old, 55±12 vs 61±18 kg, 6 M/3F vs 10 M/2F, 6/9 vs 1/12 CF and corresponding C0 PSZ exposure was 1.6±1.2 mg/L [0.4- 3.8] vs 3.0±1.5 mg/L [0.9-5.5] (p< 0 .5). Data collection range was 4 days up to 3 months after instauration. One CFLT was excluded of the analysis due to a documented failure in drug administration due to the absence of prescription renewal. Dramatic underexposure < 0.5 mg/L were never observed in the P group whereas compliance issue, occasional oral suspension administration and severe diarrhoea resulted in very low exposure in one CFLT. Previous exposures obtained with the suspension formulation in 17 CFLT in our centre were dramatically lower 0.7±0.5 mg/L with 1084±330 mg/d. The Proton pump inhibitor status was in favour of a reduced role with PSZ tablet (respectively 78% and 70% in LT and P groups).
1( 006) Change in PH Therapy from PDE5i to Riociguat Is Associated with Significant Incremental Increase in Cardiac Index, Decrease in Pulmonary Vascular Resistance and Mean Arterial Pressure R.A. Davey , A. Raina, G. Sokos, M. Kanwar, M. Patarroyo Aponte, R. Agarwal, R.L. Benza. Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA. Purpose: Pulmonary hypertension (PH) is characterized by vascular remodeling and progressive constriction. Phosphodiesterase-5 inhibitors (PDE5i) are a well studied class of pulmonary vasodilators. Recently, a soluble
guanylate cyclase stimulator, riociguat, has also been used in place of PDE5i but the benefit of switching from PDE5 to this drug has not been established. We sought to investigate the clinical and hemodynamic effects of replacing PDE5i with riociguat. Methods: We retrospectively analyzed data from patients who had been switched from a PDE5i to riociguat for a clinical indication. Baseline (prePDE5i), on PDE-5i, and post-riociguat exchange hemodynamic and clinical data were analyzed to determine if any changes were associated with riociguat exchange. Covariate analysis was performed to correct for length of time on therapy and whether other PH specific therapies had been added or intensified. Results: 18 consecutive PDE5i to riociguat switch patients were screened for inclusion and, since 5 were found to have incomplete records, 13 were included for analysis. In comparing pre-PDE5i to post-PDE5i parameters, there were no significant hemodynamic or clinical differences between the groups after a mean of 172 weeks of follow-up despite 75% of patients having other PH therapies added or intensified. However, after PDE5i to riociguat exchange for a minimum of 12 weeks (mean 34 weeks), cardiac index (CI) by Fick increased by 0.41±0.16 L/min/m2 (p= 0.026), pulmonary vascular resistance (PVR) decreased by 1.56±0.67 WU (p= 0.037) and mean arterial pressure (MAP) decreased by 19±5 mmHg (p= 0.001). Further, covariate analysis showed no significant contribution from length of time on riociguat or whether PH therapies were intensified at the time of riociguat exchange. Conclusion: We conclude that PDE5i to riociguat exchange is a viable option for patients with worsening clinical status and, after 12 weeks, is associated with significantly increased CI, decreased PVR, and decreased MAP irrespective of intensifying other PH directed therapies or extended use of the drug beyond 12 weeks. Forthcoming data from the prospective RESPITE trial may aid in further delineating this relationship. 1( 007) Survival of the PAH and CTEPH Patients in the Swedish Pulmonary Arterial Hypertension Register 2000-2014 G. Rådegran ,1 B. Kjellström,2 B. Ekmehag,3 R. Hesselstrand,4 B. Kornhall,1 F. Larsen,5 M. Nissel,6 B. Rundkvist,7 B. Ullman,8 K. Wall,9 G. Wikström,10 M. Willehadson,10 K. Jansson,11 S. Söderberg.12 1Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden; 2Cardiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden; 3Department of Public Health and Caring Science, Uppsala University, Uppsala, Sweden; 4Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden; 5Department of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institute, Stockholm, Sweden; 6Department of Medicine, Karolinska Institute, Stockholm, Sweden; 7Department of Cardiology, The Sahlgenska Academy, Gothenburg University, Gothenburg, Sweden; 8Department of Cardiology, Karolinska Institute, Stockholm, Sweden; 9Department of Clinical Physiology, Örebro University, Örebro, Sweden; 10Department of Medical Sciences Cardiology, Uppsala University, Uppsala, Sweden; 11Departments of Cardiology and Clinical Physiology, Institution of Medicine and Health Sciences, Linköping University, Linköping, Sweden; 12Department of Public Health and Clinical Medicine, Cardiology and the Heart Centre, Umeå University, Umeå, Sweden. Purpose: To define characteristics and survival of the pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients in Sweden. Methods: Incident and prevalent cases of PAH and CTEPH patients included in the Swedish Pulmonary Arterial Hypertension Register (SPAHR) between 2000 and 2014 were reviewed. Results: SPAHR included 697 PAH patients, whereof 392 were alive at the end of 2014. Median age at diagnosis was 63 years (66% female), whereof 80% were in functional-class-III-IV. Corresponding numbers for CTEPH were 247 patients, whereof 153 were alive at the end of 2014. Median age at diagnosis was 68 years (49% female), whereof 82% in functional-class-III-IV. In 2014 the prevalence of IPAH/HPAH, APAH and CTEPH were 25, 24 and 19 and the incidence 5, 2 and 3, per million inhabitants, respectively. One, three and five year survival was 78, 65 and 53% for PAH and 85, 77 and 71% for CTEPH. In the univariate analyses (Hazard ratio [95% Confidence Intervals]),
S362
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
APAH-others and APAH-CHD had a better survival compared to IPAH/ HPAH (0.35 [0.14-0.85] and 0.44 [0.25-0.78], respectively), whereas APAH-CTD had a worse survival compared to IPAH-HPAH (1.42 [1.041.92]). The differences were attenuated after adjustments for age and sex, but remained for APAH-CTD compared to IPAH-HPAH (0.60 [0.241.50], 0.74 [0.41-1.33], and (1.41 [1.03-1.94], respectively). CTEPH patients who had undergone pulmonary endarterectomy (PEA) had better survival compared to those without PEA (0.29 [0.13-0.64]), although attenuated after adjustments for age and sex (0.43 [0.18-1.02]). Survival for patients diagnosed 2005-2009 or 2010-2014 did not differ (p= 0.56), however, survival appeared worse (p< 0.01, for both) compared to those diagnosed 2000-2004. The difference between the two later compared to the first period did not remain (p greater than 0.80, for both) after adjustment for sex and age. Conclusion: The majority of PAH and CTEPH patients in Sweden were in functional-class-III-IV and 60-79 years old at diagnosis. Survival in our PAH cohort has improved compared to historical data of untreated PAH patients in the US NIH registry, and differs between PH-subgroups, but the analysis also indicates a survival bias related to prevalent vs. incident cases, comparing the time period of 2000-2004 with 2005-2009 respectively 2010-2014. 1( 008) Autologous Transfusion of Stored Red Blood Cells Impairs Endothelium-Dependent Vasodilatation in Experimental Pulmonary Arterial Hypertension. This Effect Is Reversed by Inhaled Nitric Oxide A. Rungatscher ,1 L. Daniele,1 L. San Biagio,1 S. Bombieri,1 S. Hallström,2 G. Luciani,1 G. Faggian.1 1University f Verona, Verona, Italy; 2Institute of Physiological Chemistry, University of Graz Medical School, Graz, Austria. Purpose: Transfusion with erythrocytes stored for prolonged periods increases plasma free hemoglobin (fHb), which scavenges endogenous nitric oxide (NO). The present study aimed to investigate the effects of autologous transfusion of stored erythrocytes with or without contemporary nitric oxide administered by inhalation (iNO) in a model of pulmonary arterial hypertension (PAH). Methods: PAH was induced in 30 male Wistar rats exposed to left to right shunt (Qp/Qs > 2). After 10 weeks they were randomly treated with saline (control) or with autologous erythrocytes stored for 20 days (5 ml/h) with or without iNO (30 ppm for 60 min). fHb and NO consumption was determined in plasma. Right ventricular (RV) contractility and ventricular-vascular coupling were assessed in vivo at different pre-loads by conductance catheter. Endotheliumdependent relaxation was assessed in vitro in pulmonary artery rings. Results: Results: Rats treaded with stored erythrocytes had significantly higher fHb plasma concentrations, which correlated with NO consumption (r = 0.75, p < 0.01). RV afterload expressed by effective pulmonary arterial elastance was higher in transfused rats but not in the group receiving contemporary iNO compared to control (Ea; 1.3 ± 0.5 vs 0.5 ± 0.3 vs. 0.6 ± 0.5 mm Hg/ml, respectively; p < 0.001). Ventricular-vascular coupling (Ees/Ea) was impaired after transfusion and this effect was completely abolished by iNO. Maximal endothelium-dependent relaxation in pulmonary artery was significantly attenuated in rats receiving transfusion but not in those receiving contemporary iNOS nor in the control (13.2 ± 1.5 vs. 38.5 ± 2.3 vs. 40.5 ± 2.0 %, respectively; p < 0.001). Conclusion: Transfusion with autologous stored erythrocytes worsens pulmonary arterial hypertension impairing endothelium dependent relaxation through NO scavenging by fHb. iNO completely abolish this phenomenon. 1( 009) WITHDRAWN 1( 010) Antimicrobial Activity of Cysteamine Against Antibiotic Resistant Pathogens Isolated from Cystic Fibrosis and Non- CF Patients Including Mycobacterium abscessus Complex from Lung Transplant Recipients A. Perry , J.D. Perry, C. Preece, D. Tierney, S. Peart, F.K. Gould. Microbiology Department, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Purpose: Lung transplantation for cystic fibrosis (CF) patients colonised with pan resistant bacteria, in particular M abscessus complex (MABSC) may preclude them from lung transplantation due to poor outcomes. Treatment of MABSC generally consists of a 3 drug regime including nephrotoxic/ototoxic amikacin. Oral cysteamine is licenced for treatment of cystinosis and has recently been reported as having good antimicrobial, anti-biofilm and mucolytic activity against CF pathogens. We evaluated the antimicrobial activity of this compound against a collection of 31 strains of CF and non- CF pathogens including isolates from lung transplant recipients. We also evaluated the interaction of cysteamine with 12 anti-pseudomonal agents against 4 strains P aeruginosa (Pa). Methods: Microdilution MIC’s against 12 MABSC were performed and bactericidal activity was assessed by subculture. MIC’s were performed against a collection of 19 further strains including: Pa (n= 3), Achromobacter spp. (n= 2) and 1 each of the following: Burkholderia multivorans, Burkholderia cenocepacia, Ralstonia mannitolylitica, Pandoraea sp. Stenotrophomonas maltophilia, and Inquilinus limosus. NCTC strains of E coli, S aureus; C albicans, E faecalis and 4 carbapenemase-producing Enterobacteriacae (CPE) were also evaluated. The Multiple Combination Bactericidal Test (MCBT) was utilised to assess synergy by incorporating cysteamine at 500 mg/L with 12 agents at the systemic concentration. The 4 strains selected were only susceptible to colomycin. Results: Cysteamine at 500 mg/L was bactericidal against all 4 strains of Pa and no antagonism was observed with antipseudomonal agents. The MIC’s of 12 MABSC were 256-1024 mg/L with bactericidal activity against 9 strains at 1024 mg/L and 512 mg/L for 2 strains. One strain was inhibited at 256 mg/L but no bactericidal activity observed at 1024 mg/L. The MIC’s of the 19 other isolates ranged from 64-1024 mg/L with bactericidal activity ranging from 128-1024 mg/L for all except C albicans. Conclusion: The results of this study demonstrate that cysteamine has potential as an antimicrobial for the treatment of severe infection caused by pan resistant bacteria in lung transplant patients with or without CF and warrants further evaluation. 1( 011) Posaconazole Tablets Exposure in the Real-Life of Lung Transplantation B. Douvry ,1 B. Toussaint,2 A. Roux,1 L. Lecuyer,3 E. Rivaud,1 L. Couderc,1 V. Boussaud,3 D. Grenet,1 R. Guillemain,3 E.M. Billaud.2 1Pneumology, Hosp Foch, Suresnes, France; 2Pharmacology, Hosp Georges Pompidou, Paris Cedex 15, France; 3Thoracic Transplantation, Hosp Georges Pompidou, Paris Cedex 15, France. Purpose: Appropriate exposure to Posaconazole (PSZ) was limited since the recent approval of the delayed release oral tablet formulation. Our goal is to determine the exposure obtained using the standard dose of 300 mgx1 in lung transplant patients (LT) including cystic fibrosis (CF) background. Methods: We prospectively included all patients receiving PSZ tablet 300 mgx1 under Therapeutic Drug Monitoring (TDM) evaluation performed in our centre. PSZ trough plasma concentrations (C0) were determined using LCMS assay. Indicative thresholds of interest were based on the usual < 0.5 mg/L (prophylaxis) and 0.7 mg/L (curative). Results: During June-October 2015 period, we recorded 9 LT and 12 non LT patients (P) addressed to Pneumology department from 2 centres among a multicentre cohort of over 60 patients. Respectively in LT vs P: demographics were 37.7±18.7 vs 56±17 yrs old, 55±12 vs 61±18 kg, 6 M/3F vs 10 M/2F, 6/9 vs 1/12 CF and corresponding C0 PSZ exposure was 1.6±1.2 mg/L [0.4- 3.8] vs 3.0±1.5 mg/L [0.9-5.5] (p< 0 .5). Data collection range was 4 days up to 3 months after instauration. One CFLT was excluded of the analysis due to a documented failure in drug administration due to the absence of prescription renewal. Dramatic underexposure < 0.5 mg/L were never observed in the P group whereas compliance issue, occasional oral suspension administration and severe diarrhoea resulted in very low exposure in one CFLT. Previous exposures obtained with the suspension formulation in 17 CFLT in our centre were dramatically lower 0.7±0.5 mg/L with 1084±330 mg/d. The Proton pump inhibitor status was in favour of a reduced role with PSZ tablet (respectively 78% and 70% in LT and P groups).