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102 Maintenance of Antibody Response to Pneumococcal Capsular Polysaccharide Vaccination in Adult Patients after Heart Transplantation
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
OHT), enterococcus (12% MCS; 6% OHT), and streptococcus species (8% MCS; 10% OHT). Conclusions: Major infections are common in this cohort, affecting 1/5 patients, with a majority occurring in hospital. BT was an important predictor of infection; 72% of patients with BT⬎200 min became infected. High rates of respiratory infections should guide more effective management practices. 102 Maintenance of Antibody Response to Pneumococcal Capsular Polysaccharide Vaccination in Adult Patients after Heart Transplantation E. Sarmiento,1 N. Del Pozo,1 J. Rodriguez-Molina,1 J. Navarro,1 J. Fernandez-Yañez,2 J. Palomo,2 J. Carbone.1 1Clinical Immunology, Gregorio Marañon Hospital, Madrid, Spain; 2Cardiology, Gregorio Marañon Hospital, Madrid, Spain. Purpose: The aim of this study was to evaluate the maintenance of antibody response to unconjugated pneumococcal capsular polysaccharide vaccine (PPV23) in adult heart recipients. Methods and Materials: 37 heart recipients (mean age 52⫾10) that were vaccinated with PPV23 at the time of inclusion in the waiting list, and 29 unvaccinated healthy controls (mean age 46⫾9 years) were analysed. Blood samples were taken pre-HT before vaccination (n⫽16) and after vaccination (n⫽17, mean time from vaccination: 143 days). Study points after HT: 7days (n⫽34), 1m (n⫽34), 3m (n⫽37), 6m (n⫽37), 12m (n⫽33) and 18m (n⫽22). Specific antibodies were measured using a commercial enzyme-linked immunosorbent assay technique (ELISA, Binding Site, Birmingham, UK; measuring range: 0.33-27 mg/dl). Results: In the pre-HT evaluation anti-PPS concentrations before vaccination were similar in heart recipients and controls (10⫾9 vs 10⫾8 mg/dl). After vaccination heart recipients disclosed significantly higher concentrations than controls: before HT (27⫾0.9, p⬍0.001,) and at 7days (20⫾8, p⬍0.001), 1m (19⫾9, p⬍0.001), 3m (18⫾9, p⬍0.001), 6m (16⫾9, p⫽0.005), and 12m (14⫾9, p⫽0.045) after-HT. There were no significant differences between both groups at 18m (12⫾9, p⫽0.21). Median fold increase of anti-PPS was 4.56 (pre-HT vs 7 days, interval: 0.54-17.42). There was a progressive decrease in anti-PPS which were significantly lower as compared with baseline post-vaccination values at all post-HT study points. During follow-up, 8 patients (20.5%) developed bacterial infectious complications. The frequency of heart recipients that maintained anti-PPS concentrations higher than 27 mg/dl during the first 3 months was 12.5% and 48% in patients with and without bacterial infections, respectively (p⫽0.07). Conclusions: Heart recipients maintained higher concentrations of antiPPS as compared with unvaccinated healthy controls up to 18 months after transplantation. Lower concentrations of anti-PPS mignt be associated with development of bacterial infections. 103 Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas Aeruginosa H.N. Haja Mydin,1 P.A. Corris,1,3 G. Meachery,1 A. Nicholson,2 S. Peart,2 C. Fagan,2 J.L. Lordan,1,3 A.J. Fisher,1,3 F.K. Gould.2 1 Department of Cardiopulmonary Transplantation, The Freeman Hospital, Newcastle upon Tyne, United Kingdom; 2Department of Medical Microbiology, The Freeman Hospital, Newcastle upon Tyne, United Kingdom; 3Transplantation and Immunobiology Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. Purpose: Early infection is a recognised complication following lung transplantation in patients with cystic fibrosis (CF). Our centre currently advocates the use of multiple combination bactericidal testing (synergy testing) when determining appropriate prophylactic regimens. To evaluate our strategy, we compared the rates of infection post-transplant in patients whose peri-transplant anti-microbial regimens were determined using the synergy method versus conventional means. Methods and Materials: Patients with CF who underwent lung transplantations between 2000 and 2010 were identified. Data was collected retrospectively from patients’ records to collate post-transplant clinical information. Our microbiology database was interrogated to identify
microorganisms cultured from the patients. These were mapped against antibiotic resistance, method of sensitivity testing and choice of antibiotics that were administered. Results: Between 27/01/2000 and 23/08/2010, 129 lung transplants were performed on patients with CF and Pseudomonas aeruginosa colonisation (mean age 28, male: female, 63:66). Synergy testing was gradually introduced from October 2001 and became the default method from May 2008. Fifty patients were given antibiotics that were chosen based on synergy testing. There were 79 patients in the conventional group. Two patients who were synergy-tested developed septicaemia within 30 days, compared to 13 in the conventional group (p⬍0.05, 2-tailed Fisher’s test). One patient who was synergy-tested was noted to have bacterial growth in the posttransplant pleural effusion, as opposed to 10 in the conventional group (p⬍0.05). There were no statistically significant differences in overall mortality rate at 30 days and at 1 year. Conclusions: Patients who were given antibiotics based on synergy testing had significantly lower rates of septicaemia and lower rates of positive microbiological cultures in their pleural effusions. 104 Reduced Lifetime Incidence of Cytomegalovirus with Extended Prophylaxis: Long-Term Follow Up from a Randomized Controlled Trial C.A. Finlen Copeland,1 W.A. Davis,1 L.D. Snyder,1 M. Banks,2 R. Avery,3 S.M. Palmer.1,2 1Medicine, Duke University Medical Center, Durham, NC; 2Duke Clinical Research Institute, Durham, NC; 3 Medicine, Cleveland Clinic, Cleveland, OH. Purpose: The optimal approach to cytomegalovirus (CMV) prevention in lung transplant recipients is controversial. We recently completed the only randomized placebo-controlled study of CMV prevention in lung transplantation and demonstrated the short-term efficacy and safety of 12 months of valganciclovir prophylaxis (extended therapy) as compared to 3 months (shortcourse therapy). To examine whether extended therapy provides a long-term benefit we followed a single center subset of patients enrolled in the trial and assessed their lifetime incidence of CMV and hematological abnormalities. Methods and Materials: All randomized patients (n⫽38) from Duke Medical Center were included in the follow-up analysis. All patients underwent consistent serial serum CMV monitoring and surveillance bronchoscopy. CMV was defined by either viremia (⬎500 CMV DNA copies/ ml) or pneumonitis. Safety was assessed by review of all posttransplant complete blood counts. Results: Over a mean follow-up time of 4 years in each group, extended as compared to short-course therapy led to a significant lifetime reduction in CMV (12% vs. 55%, respectively, p ⫽ 0.009, HR ⫽ 0.13, 95% CI ⫽ 0.03-0.61). The groups underwent a comparable number of peripheral blood draws and bronchoscopies to screen for CMV. White blood cell, neutrophil, and platelet counts were similar between treatment groups over posttransplant follow-up. Conclusions: Extending valganciclovir prophylaxis to 12 months after lung transplantation significantly reduces the lifetime incidence of CMV by preventing most late onset disease, as compared to 3 months. Until immune based CMV risk assessments are implemented to determine the optimal individualized duration of prophylaxis, the use of 12 months is an effective and safe way to reduce the lifetime burden of CMV. 105 Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis D. Mitsani, H. Nguyen, R. Shields, Y. Toyoda, J. Bhama, E. Kwak, F. Silveira, J. Pilewski, M. Crespo, C. Clancy. University of Pittsburgh, Pittsburgh. Purpose: Voriconazole therapeutic drug monitoring (VOR TDM) is advocated in patients (pts) treated for invasive fungal infections (IFI). Associations between VOR levels and outcomes among lung transplant (LTx) recipients receiving VOR prophylaxis (px) are unclear. Methods and Materials: Prospective, observational study of LTx pts receiving VOR px from Jan-Dec 2009 (2 doses IV (6 mg/kg) then 200 mg po BID). TDM was performed by HPLC, beginning after ⱖ7 d of px.
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
OHT), enterococcus (12% MCS; 6% OHT), and streptococcus species (8% MCS; 10% OHT). Conclusions: Major infections are common in this cohort, affecting 1/5 patients, with a majority occurring in hospital. BT was an important predictor of infection; 72% of patients with BT⬎200 min became infected. High rates of respiratory infections should guide more effective management practices. 102 Maintenance of Antibody Response to Pneumococcal Capsular Polysaccharide Vaccination in Adult Patients after Heart Transplantation E. Sarmiento,1 N. Del Pozo,1 J. Rodriguez-Molina,1 J. Navarro,1 J. Fernandez-Yañez,2 J. Palomo,2 J. Carbone.1 1Clinical Immunology, Gregorio Marañon Hospital, Madrid, Spain; 2Cardiology, Gregorio Marañon Hospital, Madrid, Spain. Purpose: The aim of this study was to evaluate the maintenance of antibody response to unconjugated pneumococcal capsular polysaccharide vaccine (PPV23) in adult heart recipients. Methods and Materials: 37 heart recipients (mean age 52⫾10) that were vaccinated with PPV23 at the time of inclusion in the waiting list, and 29 unvaccinated healthy controls (mean age 46⫾9 years) were analysed. Blood samples were taken pre-HT before vaccination (n⫽16) and after vaccination (n⫽17, mean time from vaccination: 143 days). Study points after HT: 7days (n⫽34), 1m (n⫽34), 3m (n⫽37), 6m (n⫽37), 12m (n⫽33) and 18m (n⫽22). Specific antibodies were measured using a commercial enzyme-linked immunosorbent assay technique (ELISA, Binding Site, Birmingham, UK; measuring range: 0.33-27 mg/dl). Results: In the pre-HT evaluation anti-PPS concentrations before vaccination were similar in heart recipients and controls (10⫾9 vs 10⫾8 mg/dl). After vaccination heart recipients disclosed significantly higher concentrations than controls: before HT (27⫾0.9, p⬍0.001,) and at 7days (20⫾8, p⬍0.001), 1m (19⫾9, p⬍0.001), 3m (18⫾9, p⬍0.001), 6m (16⫾9, p⫽0.005), and 12m (14⫾9, p⫽0.045) after-HT. There were no significant differences between both groups at 18m (12⫾9, p⫽0.21). Median fold increase of anti-PPS was 4.56 (pre-HT vs 7 days, interval: 0.54-17.42). There was a progressive decrease in anti-PPS which were significantly lower as compared with baseline post-vaccination values at all post-HT study points. During follow-up, 8 patients (20.5%) developed bacterial infectious complications. The frequency of heart recipients that maintained anti-PPS concentrations higher than 27 mg/dl during the first 3 months was 12.5% and 48% in patients with and without bacterial infections, respectively (p⫽0.07). Conclusions: Heart recipients maintained higher concentrations of antiPPS as compared with unvaccinated healthy controls up to 18 months after transplantation. Lower concentrations of anti-PPS mignt be associated with development of bacterial infections. 103 Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas Aeruginosa H.N. Haja Mydin,1 P.A. Corris,1,3 G. Meachery,1 A. Nicholson,2 S. Peart,2 C. Fagan,2 J.L. Lordan,1,3 A.J. Fisher,1,3 F.K. Gould.2 1 Department of Cardiopulmonary Transplantation, The Freeman Hospital, Newcastle upon Tyne, United Kingdom; 2Department of Medical Microbiology, The Freeman Hospital, Newcastle upon Tyne, United Kingdom; 3Transplantation and Immunobiology Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. Purpose: Early infection is a recognised complication following lung transplantation in patients with cystic fibrosis (CF). Our centre currently advocates the use of multiple combination bactericidal testing (synergy testing) when determining appropriate prophylactic regimens. To evaluate our strategy, we compared the rates of infection post-transplant in patients whose peri-transplant anti-microbial regimens were determined using the synergy method versus conventional means. Methods and Materials: Patients with CF who underwent lung transplantations between 2000 and 2010 were identified. Data was collected retrospectively from patients’ records to collate post-transplant clinical information. Our microbiology database was interrogated to identify
microorganisms cultured from the patients. These were mapped against antibiotic resistance, method of sensitivity testing and choice of antibiotics that were administered. Results: Between 27/01/2000 and 23/08/2010, 129 lung transplants were performed on patients with CF and Pseudomonas aeruginosa colonisation (mean age 28, male: female, 63:66). Synergy testing was gradually introduced from October 2001 and became the default method from May 2008. Fifty patients were given antibiotics that were chosen based on synergy testing. There were 79 patients in the conventional group. Two patients who were synergy-tested developed septicaemia within 30 days, compared to 13 in the conventional group (p⬍0.05, 2-tailed Fisher’s test). One patient who was synergy-tested was noted to have bacterial growth in the posttransplant pleural effusion, as opposed to 10 in the conventional group (p⬍0.05). There were no statistically significant differences in overall mortality rate at 30 days and at 1 year. Conclusions: Patients who were given antibiotics based on synergy testing had significantly lower rates of septicaemia and lower rates of positive microbiological cultures in their pleural effusions. 104 Reduced Lifetime Incidence of Cytomegalovirus with Extended Prophylaxis: Long-Term Follow Up from a Randomized Controlled Trial C.A. Finlen Copeland,1 W.A. Davis,1 L.D. Snyder,1 M. Banks,2 R. Avery,3 S.M. Palmer.1,2 1Medicine, Duke University Medical Center, Durham, NC; 2Duke Clinical Research Institute, Durham, NC; 3 Medicine, Cleveland Clinic, Cleveland, OH. Purpose: The optimal approach to cytomegalovirus (CMV) prevention in lung transplant recipients is controversial. We recently completed the only randomized placebo-controlled study of CMV prevention in lung transplantation and demonstrated the short-term efficacy and safety of 12 months of valganciclovir prophylaxis (extended therapy) as compared to 3 months (shortcourse therapy). To examine whether extended therapy provides a long-term benefit we followed a single center subset of patients enrolled in the trial and assessed their lifetime incidence of CMV and hematological abnormalities. Methods and Materials: All randomized patients (n⫽38) from Duke Medical Center were included in the follow-up analysis. All patients underwent consistent serial serum CMV monitoring and surveillance bronchoscopy. CMV was defined by either viremia (⬎500 CMV DNA copies/ ml) or pneumonitis. Safety was assessed by review of all posttransplant complete blood counts. Results: Over a mean follow-up time of 4 years in each group, extended as compared to short-course therapy led to a significant lifetime reduction in CMV (12% vs. 55%, respectively, p ⫽ 0.009, HR ⫽ 0.13, 95% CI ⫽ 0.03-0.61). The groups underwent a comparable number of peripheral blood draws and bronchoscopies to screen for CMV. White blood cell, neutrophil, and platelet counts were similar between treatment groups over posttransplant follow-up. Conclusions: Extending valganciclovir prophylaxis to 12 months after lung transplantation significantly reduces the lifetime incidence of CMV by preventing most late onset disease, as compared to 3 months. Until immune based CMV risk assessments are implemented to determine the optimal individualized duration of prophylaxis, the use of 12 months is an effective and safe way to reduce the lifetime burden of CMV. 105 Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis D. Mitsani, H. Nguyen, R. Shields, Y. Toyoda, J. Bhama, E. Kwak, F. Silveira, J. Pilewski, M. Crespo, C. Clancy. University of Pittsburgh, Pittsburgh. Purpose: Voriconazole therapeutic drug monitoring (VOR TDM) is advocated in patients (pts) treated for invasive fungal infections (IFI). Associations between VOR levels and outcomes among lung transplant (LTx) recipients receiving VOR prophylaxis (px) are unclear. Methods and Materials: Prospective, observational study of LTx pts receiving VOR px from Jan-Dec 2009 (2 doses IV (6 mg/kg) then 200 mg po BID). TDM was performed by HPLC, beginning after ⱖ7 d of px.