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Combined Short Term Caspofungin and Nebulized Amphotericin B Prophylaxis May Help To Eradicate Aspergillus Related Complications After Lung Transplantation
S180
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
5 Year Actuarial Survival 5 Year Freedom From CAV 5 Year Freedom From NF-MACE *p< 0.05
D-/R(n= 693)
D-/R+ (n= 69)
D+/R(n= 18)
D+/R+ (n= 5)
87.3% 81.5% 82.7%
87.0% 85.5% 88.4%
72.2%* 88.9% 83.3%
80.0% 100.0% 100.0%
compared to control (D-/R-) group
4( 79) Combined Short Term Caspofungin and Nebulized Amphotericin B Prophylaxis May Help To Eradicate Aspergillus Related Complications After Lung Transplantation P.T. Hammainen ,1 M. Eriksson,2 M. Halme,3 K. Lemstrom.1 1Cardiac Surgery, Helsinki Heart and Lung Center, Helsinki, Finland; 2Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland; 3Department of Pulmonology, Helsinki Heart and Lung Center, Helsinki, Finland. Purpose: Early treatment strategies in our institute resulted 10% invasive Aspergillus (IA) mortality within the first posttransplant year. Despite the incidence of IA is lower nowadays, a wide variety of related complications, like posttransplant tracheobronchitis, anastomotic and airway complications requiring interventions, invasive pulmonary disease, fistulas, surgical site infections, endocarditis and systemic spread of IA are reported. The aim of this retrospective study was to evaluate the outcomes of a combined systemic caspofungin and nebulized Amphotericin B (nAmB) prophylaxis. Methods: We followed 96 consecutive double lung transplant patients operated on between 2007-12. This series include 7 re- or re-re-transplantations and 13 patients bridged to transplantation using ECMO. With few exceptions, routine antifungal prophylaxis consisted of caspofungin 50 mg iv. at induction and second dose 24 hours later. nAmB was started immediately in ICU, and nAmphoricin B lipid complex was continued once a week until re-epithelisation of the bronchial anastomosis was complete. The endpoints were postoperative Aspergillus colonization or disease or death due to any cause, or airway complication requiring intervention. Results: The respective 30 day and 1 year survivals were 99% and 97%. The antifungal prophylactic regimens were safe and well tolerated. 93% of patients were alive at the end of the follow up (aver. 3.0 years). No clinically confirmed IA infections occurred. Postoperative colonization was rare. No airway complications requiring dilatation or stents were detected. Preoperative Aspergillus colonization/disease was not a risk factor for death. Conclusion: This is the first report of Aspergillus prophylaxis using the combination of caspofungin and nebulized Amphotericin B. This prophylaxis was associated with a very low number of complications. The correct timing, systemic coverage, synergistic effect and minimal toxicity of the prophylaxis are considered highly important. The effect of surgical techniques, tailored immunosuppression and postoperative colonization in regards to development of BOS will be discussed. 4( 80) Analysis of Incidence and Risk Factors for Polyomavirus Infection after Lung Transplant B. Adams ,1 A.T. Logan,2 T. Haddad.3 1Pharmacy, Tampa General Hospital, Tampa, FL; 2Tampa General Hospital, Tampa, FL; 3New Lung Associates, Tampa, FL. Purpose: BK virus (BKV) and JC virus (JCV) are polyomaviruses (PV) that are well reported in kidney transplant as possible causes of renal dysfunction and graft loss, however, is less studied in the non-renal transplants. Renal dysfunction is a late complication after lung transplant due to multi-factorial causes. This study aims to investigate the incidence of PV viruria, viremia, and risk factors for PV reactivation (PVR). Methods: This was a single centered, retrospective case-control study. 156 patients received a lung transplant between 7/2009-8/2012 and patients between the ages 18-75 years old were included and matched at a 1:3 ratio (case = PVR:control= no PVR) for indication, age, single vs. double lung, and sex. Data collected include demographics, PV PCRs, tacrolimus levels, and serum creatinine (SCr). Incidence of PV viruria and viremia were determined and an
analysis was performed to compare baseline demographics, renal function, prograf troughs, and immunosuppression induction between the two groups. Results: PV viruria was detected in 18 of 156 patients (12%), n= 9 BKV, and n= 9 JCV. PV viremia was detected in 5 patients (3%), [BKV n= 3 and JCV n= 2] and no renal biopsies were performed to assess biopsy proven PV nephropathy. 18 patients were in the case group with 38 matched controls. No significant differences were found in baseline demographics, SCr, tacrolimus levels, induction agent, cylex levels, or rejection. Time to PVR occurred at a median of 335 days. Mean SCr at 3,6,12,and 18 months showed statistically significant increases in the case versus control group respectively (1.2 vs. 0.9, p= 0.020), at 6 months (1.4 vs 1.0, p= 0.017), at 12 months (1.7 vs. 1.3, p= 0.036), and at 18 months (2.1 vs.1.5, p= 0.049). Conclusion: The results show a similar incidence in viral shedding of both BKV and JCV with an overall 3% incidence of viremia. A significant increase in SCr was seen in the patients who developed PV reactivation which may implicate early renal dysfunction with increased risk of PV reactivation. The results support that early screening of polyomavirus should be considered when early renal dysfunction is observed in lung transplant recipients. 4( 81) Cytomegalovirus Infection Following Lung Transplantation Occurrence, Treatment and Risk of OB D. Thomas , A.J. Wilkinson, L. Succony, S. Tsui. Transplant Directorate, Papworth Hospital, Papworth Everard, United Kingdom. Purpose: 1. To review our incidence, prophylaxis and treatment of cytomegalovirus (CMV) infection in lung transplant patients 2. To identify if CMV reactivation (viral load > 3000copies/ml) is associated with poorer long term outcome, specifically an increased risk of bronchiolitis obliterans syndrome (BOS) and mortality. Methods: A retrospective review of the notes of patients who underwent lung transplantation between 2007-09 with data collected for 3 years post transplantation. Results: Of 80 patients transplanted 62 were eligible for inclusion - 10 were excluded as they died within 6 months (none due to CMV) and 8 had incomplete data. All patients received standard 3 agent immunosupression and none received induction therapy. 25 (40%) were CMV donor and recipient negative (R-/D-) and acted as a control. 37 (60%) had CMV exposure; 12 R+/D+; 14 R-/D+; 11 R+/D-. All 37 exposed patients received Valganciclovir 450mg od prophylaxis for an average of 3 months and no reactivation was seen whilst on prophylaxis. CMV reactivation There were no cases of CMV in the control group but 60% (n= 22) had CMV reactivation in the exposed groups - a higher rate than in other series at this centre (25% historical data). Treatment for CMV reactivation was 45% (n= 10) received IV Ganciclovir for an average 7 days, 32% (n= 7) had oral Valganciclovir and 13% (n= 5) received no treatment. Freedom from BOS and three year survival CMV reactivation was associated with a significantly increased rate of BOS at 3 years (66% vs 10% p= 0.034) compared with the control group. A trend towards lower three year survival was seen following CMV reactivation (73% vs 84%). Conclusion: CMV reactivation in exposed patients undergoing lung transplantation was surprisingly high and was associated with a significantly higher risk of subsequent BOS and a trend towards a poorer 3 year survival. Our prophylaxis regime has since extended to six months which may reduce CMV incidence and improve long term outcomes.
Freedom from BOS and survival following lung transplantation according to CMV status. Conditional freedom from BOS at 1 year Control group 24/25 (95%) (R-/D-) (n= 25) CMV exposure but 15/15 (100%) no reactivation (n= 15) CMV exposure with 14/21 (67%) reactivation (n= 22)
Conditional freedom from BOS at 3 years 19/21 (90%)
*
3 year survival 18/21 (84%)
10/14 (71%)
13/14 (93%)
7/16 (44%) p= 0.034
16/22 (73%)
*
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
5 Year Actuarial Survival 5 Year Freedom From CAV 5 Year Freedom From NF-MACE *p< 0.05
D-/R(n= 693)
D-/R+ (n= 69)
D+/R(n= 18)
D+/R+ (n= 5)
87.3% 81.5% 82.7%
87.0% 85.5% 88.4%
72.2%* 88.9% 83.3%
80.0% 100.0% 100.0%
compared to control (D-/R-) group
4( 79) Combined Short Term Caspofungin and Nebulized Amphotericin B Prophylaxis May Help To Eradicate Aspergillus Related Complications After Lung Transplantation P.T. Hammainen ,1 M. Eriksson,2 M. Halme,3 K. Lemstrom.1 1Cardiac Surgery, Helsinki Heart and Lung Center, Helsinki, Finland; 2Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland; 3Department of Pulmonology, Helsinki Heart and Lung Center, Helsinki, Finland. Purpose: Early treatment strategies in our institute resulted 10% invasive Aspergillus (IA) mortality within the first posttransplant year. Despite the incidence of IA is lower nowadays, a wide variety of related complications, like posttransplant tracheobronchitis, anastomotic and airway complications requiring interventions, invasive pulmonary disease, fistulas, surgical site infections, endocarditis and systemic spread of IA are reported. The aim of this retrospective study was to evaluate the outcomes of a combined systemic caspofungin and nebulized Amphotericin B (nAmB) prophylaxis. Methods: We followed 96 consecutive double lung transplant patients operated on between 2007-12. This series include 7 re- or re-re-transplantations and 13 patients bridged to transplantation using ECMO. With few exceptions, routine antifungal prophylaxis consisted of caspofungin 50 mg iv. at induction and second dose 24 hours later. nAmB was started immediately in ICU, and nAmphoricin B lipid complex was continued once a week until re-epithelisation of the bronchial anastomosis was complete. The endpoints were postoperative Aspergillus colonization or disease or death due to any cause, or airway complication requiring intervention. Results: The respective 30 day and 1 year survivals were 99% and 97%. The antifungal prophylactic regimens were safe and well tolerated. 93% of patients were alive at the end of the follow up (aver. 3.0 years). No clinically confirmed IA infections occurred. Postoperative colonization was rare. No airway complications requiring dilatation or stents were detected. Preoperative Aspergillus colonization/disease was not a risk factor for death. Conclusion: This is the first report of Aspergillus prophylaxis using the combination of caspofungin and nebulized Amphotericin B. This prophylaxis was associated with a very low number of complications. The correct timing, systemic coverage, synergistic effect and minimal toxicity of the prophylaxis are considered highly important. The effect of surgical techniques, tailored immunosuppression and postoperative colonization in regards to development of BOS will be discussed. 4( 80) Analysis of Incidence and Risk Factors for Polyomavirus Infection after Lung Transplant B. Adams ,1 A.T. Logan,2 T. Haddad.3 1Pharmacy, Tampa General Hospital, Tampa, FL; 2Tampa General Hospital, Tampa, FL; 3New Lung Associates, Tampa, FL. Purpose: BK virus (BKV) and JC virus (JCV) are polyomaviruses (PV) that are well reported in kidney transplant as possible causes of renal dysfunction and graft loss, however, is less studied in the non-renal transplants. Renal dysfunction is a late complication after lung transplant due to multi-factorial causes. This study aims to investigate the incidence of PV viruria, viremia, and risk factors for PV reactivation (PVR). Methods: This was a single centered, retrospective case-control study. 156 patients received a lung transplant between 7/2009-8/2012 and patients between the ages 18-75 years old were included and matched at a 1:3 ratio (case = PVR:control= no PVR) for indication, age, single vs. double lung, and sex. Data collected include demographics, PV PCRs, tacrolimus levels, and serum creatinine (SCr). Incidence of PV viruria and viremia were determined and an
analysis was performed to compare baseline demographics, renal function, prograf troughs, and immunosuppression induction between the two groups. Results: PV viruria was detected in 18 of 156 patients (12%), n= 9 BKV, and n= 9 JCV. PV viremia was detected in 5 patients (3%), [BKV n= 3 and JCV n= 2] and no renal biopsies were performed to assess biopsy proven PV nephropathy. 18 patients were in the case group with 38 matched controls. No significant differences were found in baseline demographics, SCr, tacrolimus levels, induction agent, cylex levels, or rejection. Time to PVR occurred at a median of 335 days. Mean SCr at 3,6,12,and 18 months showed statistically significant increases in the case versus control group respectively (1.2 vs. 0.9, p= 0.020), at 6 months (1.4 vs 1.0, p= 0.017), at 12 months (1.7 vs. 1.3, p= 0.036), and at 18 months (2.1 vs.1.5, p= 0.049). Conclusion: The results show a similar incidence in viral shedding of both BKV and JCV with an overall 3% incidence of viremia. A significant increase in SCr was seen in the patients who developed PV reactivation which may implicate early renal dysfunction with increased risk of PV reactivation. The results support that early screening of polyomavirus should be considered when early renal dysfunction is observed in lung transplant recipients. 4( 81) Cytomegalovirus Infection Following Lung Transplantation Occurrence, Treatment and Risk of OB D. Thomas , A.J. Wilkinson, L. Succony, S. Tsui. Transplant Directorate, Papworth Hospital, Papworth Everard, United Kingdom. Purpose: 1. To review our incidence, prophylaxis and treatment of cytomegalovirus (CMV) infection in lung transplant patients 2. To identify if CMV reactivation (viral load > 3000copies/ml) is associated with poorer long term outcome, specifically an increased risk of bronchiolitis obliterans syndrome (BOS) and mortality. Methods: A retrospective review of the notes of patients who underwent lung transplantation between 2007-09 with data collected for 3 years post transplantation. Results: Of 80 patients transplanted 62 were eligible for inclusion - 10 were excluded as they died within 6 months (none due to CMV) and 8 had incomplete data. All patients received standard 3 agent immunosupression and none received induction therapy. 25 (40%) were CMV donor and recipient negative (R-/D-) and acted as a control. 37 (60%) had CMV exposure; 12 R+/D+; 14 R-/D+; 11 R+/D-. All 37 exposed patients received Valganciclovir 450mg od prophylaxis for an average of 3 months and no reactivation was seen whilst on prophylaxis. CMV reactivation There were no cases of CMV in the control group but 60% (n= 22) had CMV reactivation in the exposed groups - a higher rate than in other series at this centre (25% historical data). Treatment for CMV reactivation was 45% (n= 10) received IV Ganciclovir for an average 7 days, 32% (n= 7) had oral Valganciclovir and 13% (n= 5) received no treatment. Freedom from BOS and three year survival CMV reactivation was associated with a significantly increased rate of BOS at 3 years (66% vs 10% p= 0.034) compared with the control group. A trend towards lower three year survival was seen following CMV reactivation (73% vs 84%). Conclusion: CMV reactivation in exposed patients undergoing lung transplantation was surprisingly high and was associated with a significantly higher risk of subsequent BOS and a trend towards a poorer 3 year survival. Our prophylaxis regime has since extended to six months which may reduce CMV incidence and improve long term outcomes.
Freedom from BOS and survival following lung transplantation according to CMV status. Conditional freedom from BOS at 1 year Control group 24/25 (95%) (R-/D-) (n= 25) CMV exposure but 15/15 (100%) no reactivation (n= 15) CMV exposure with 14/21 (67%) reactivation (n= 22)
Conditional freedom from BOS at 3 years 19/21 (90%)
*
3 year survival 18/21 (84%)
10/14 (71%)
13/14 (93%)
7/16 (44%) p= 0.034
16/22 (73%)
*