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Viral Pneumonia Accelerates Graft Death and CLAD in Lung Transplant Recipients
Abstracts S305 9/14 patients with active disease received combination therapy as follows (mean +/- SD treatment time in months): 6 with Cefoxitin (6.6 +/- 6), 7 with Amikacin (5.6 +/- 5.5), 5 with Macrolides (7.5 +/- 5.6), 2 with Imipenem (4.7 +/- 1.7), 2 with Clofazamine (4.5 +/- 2.1), 6 with Tygecycline (2.9 +/1.4), 1 with Linezolid. 6/9 had reduction in immunosuppression. 6 patients responded to treatment with no recurrence; among those 4 underwent surgical debridement. Five patients died (35%). Survival time from transplant to death was 25.5 +/- 37.3 months; survival from MA detection to death was 6 +/- 3.3 months. Four patients developed acute cellular rejection (mean time to development 2.85 +/- 0.7 months), all after detection of MA and non-recurrent. Conclusion: Mycobacterium Abscessus is uncommon infectious complication of transplant, it carries significant mortality. Allografts are involved in most cases, skin lesions are common. Surgical debridement in our cohort had better outcomes. Future studies should evaluate optimal therapy of MA in an immunosuppressed population, and the relationship between MA and rejection.
Table 1. Patient characteristics.
Gender Male Female Transplant Type Single Bilateral Diagnosis COPD Cystic Fibrosis Sarcoidosis IPF A1T1 Langerhans Cell Histiocytosis Non-CF bronchiectasis
Number
%
12 2
85.7 14.3
3 11
21.4 78.6
4 3 2 2 1 1 1
28.6 21.4 14.3 14.3 7.1 7.1 7.1
8( 39) Viral Pneumonia Accelerates Graft Death and CLAD in Lung Transplant Recipients P.R. Allyn ,1 E.L. Duffy,2 R.M. Humphries,3 R. Saggar,4 S.S. Weight,4 J.A. Belperio,4 C. Tseng,2 A.L. Gregson.1 1Department of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, CA; 2Department of Medicine, Statistics Core, University of California Los Angeles, Los Angeles, CA; 3Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA; 4Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA. Purpose: Community acquired respiratory virus (CARV) infections occur frequently after lung transplantation. We hypothesized that severe infection would increase the risk of chronic allograft dysfunction and graft death, while asymptomatic carriage would not. Methods: We retrospectively reviewed all lung transplant recipients between January 2000 and July 2013 at the University of California, Los Angeles. Bronchoscopy was performed according to a surveillance protocol at 1 day, 1 week, 1, 3, 6, and 12 months post-transplant. Additional samples were sent from bronchoscopy, sputum, and nasopharyngeal washes when clinically indicated. CARV pneumonia was defined as a positive viral test with symptoms and a consistent radiographic infiltrate. Graft death was defined as patient death or re-transplant. BOS was defined according to International Society for Heart and Lung Transplantation (ISHLT) guidelines. We used multivariate Cox modeling to assess the relationship between CARV infection and outcomes. Results: Of 563 total patients, 139 produced 324 positive specimens in 245 episodes of viral infection (repeat samples within 30 days were excluded). The most frequently isolated viruses were coxsackie/echovirus (20.4%), rhinovirus/enterovirus (19.2%), parainfluenza (18.4%), coronavirus (14.3%), and human metapneumovirus (8.2%). The overall risk of CLAD was elevated
with any CARV infection (HR 1.79, p < 0.01), though when analyzed as parallel predictors in subgroup analysis, only clinical pneumonia remained statistically significant (HR 1.64, p = 0.03). Asymptomatic viral infection (HR 1.50, p = 0.08) and symptomatic viral infection (HR 1.03, p = 0.91) did not meet statistical significance. Viral pneumonia significantly increased the risk of graft death (HR 2.58, p < 0.01). However, overall CARV infection (HR 0.92, p = 0.60), asymptomatic CARV infection (HR 0.76, p = 0.24), and symptomatic CARV infection (HR 0.78, p = 0.42) did not. Conclusion: Viral pneumonia increases the risk of graft death and CLAD after lung transplantation. Overall CARV infections also appear to increase the risk of CLAD, although in our cohort this risk was primarily driven by those with viral pneumonia. Asymptomatic viral carriage and symptomatic CARV infection without pneumonia did not appear to impact graft survival. 8( 40) Everolimus and Valganciclovir Prophylaxis: How to Chase CMV But Not the Patient: Insights From PROTECT Randomized Study B. Perciaccante,1 G. Bianchi,1 L. Potena ,1 P. Prestinenzi,1 A. Chiereghin,2 T. Lazzarotto,2 M. Masetti,1 C. Rapezzi,1 G. Magnani,1 F. Grigioni.1 1Heart and Lung Transplant Program, University of Bologna, Bologna, Italy; 2Microbiology Department, University of Bologna, Bologna, Italy. Purpose: Cytomegalovirus (CMV) infection may influence the development of Cardiac Allograft Vasculopathy (CAV). In this prospective randomized study we aimed to analyze the interplay of immunosuppressive, anti-CMV strategies and CMV immunity on the risk for CMV infection and CAV during the first year after transplant. Methods: By a 2x2 randomization process, CMV seropositive heart transplant (HT) recipients were randomized to receive 3 months of valganciclovir prophylaxis (PRO) or a pre-emptive based approach (PRE), and to receive mycophenolate (MMF) or everolimus (EVE) on top of a cyclosporine-based immunosuppressive therapy. All were monitored for CMV infection by whole blood PCR and CMV-immunity reconstitution by elispot assay. At month 1 and 12 after transplant eligible patients underwent intravascular ultrasound (IVUS). Occurrence of CMV infection and change in maximal intimal thickness (MIT) > 0.5mm were study endpoints. Results: Forty-six patients were randomized: 22 to PRE vs. 24 to PRO, and 24 to EVE vs. 22 to MMF. Six (25%) patients discontinued EVE and 13 (54%) did not completed the 3-months period of PRO for adverse events (mainly effusions in EVE and leucopenia in PRO). Only 23 patients underwent IVUS both at month 1 and month 12. After adjusting for donor serology, PRO and EVE were associated with reduced risk of 70 and 54% respectively for CMV infection in the intention to treat (ITT) analysis (P< 0.05). However, EVE discontinuation and lack of PRO completion were associated with increased risk for CMV infection. Only 4 (17%) patients developed the MIT endpoint, not allowing any conclusion about treatments efficacy. Nevertheless 100% of the patients who discontinued EVE developed the MIT endpoint. Recovery of CMV immunity at month 1 by Elispot analysis allowed stratifying the risk for CMV infection: patients with lack of immunity were at higher risk of infection, and most likely to benefit from PRO or EVE (P< 0.01). Conclusion: EVE and PRO are protective from CMV infection, but a significant percentage of patients discontinued the treatments for intolerance and appear to be exposed to higher risk of events. Analysis of CMV immunity recovery may provide guidance in customizing therapeutic strategies, by identifying patients in whom aggressive anti-CMV strategies may have a favorable risk/benefit ratio. 8( 41) Hepatitis B Vaccination in Heart Transplant Recipients: Response Rate and Risk Factors for Loss of Immunity E.S. Sukerman ,1 I. Echenique,2 M. Angarone,1 R. Gordon,3 A. Anderson,3 J. Rich,3 A. Sauer,3 T. Abicht,4 V. Stosor.1 1Infectious Diseases, Northwestern University, Chicago, IL; 2Infectious Diseases, Cleveland Clinic, Weston, FL; 3Cardiology, Northwestern University, Chicago, IL; 4Cardiac Surgery, Northwestern University, Chicago, IL. Purpose: To examine pre-heart transplant (HT) hepatitis B virus (HB) immunization completion and response rates and identify risk factors for loss of HB immunity after HT.
Table 1. Patient characteristics.
Gender Male Female Transplant Type Single Bilateral Diagnosis COPD Cystic Fibrosis Sarcoidosis IPF A1T1 Langerhans Cell Histiocytosis Non-CF bronchiectasis
Number
%
12 2
85.7 14.3
3 11
21.4 78.6
4 3 2 2 1 1 1
28.6 21.4 14.3 14.3 7.1 7.1 7.1
8( 39) Viral Pneumonia Accelerates Graft Death and CLAD in Lung Transplant Recipients P.R. Allyn ,1 E.L. Duffy,2 R.M. Humphries,3 R. Saggar,4 S.S. Weight,4 J.A. Belperio,4 C. Tseng,2 A.L. Gregson.1 1Department of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, CA; 2Department of Medicine, Statistics Core, University of California Los Angeles, Los Angeles, CA; 3Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA; 4Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA. Purpose: Community acquired respiratory virus (CARV) infections occur frequently after lung transplantation. We hypothesized that severe infection would increase the risk of chronic allograft dysfunction and graft death, while asymptomatic carriage would not. Methods: We retrospectively reviewed all lung transplant recipients between January 2000 and July 2013 at the University of California, Los Angeles. Bronchoscopy was performed according to a surveillance protocol at 1 day, 1 week, 1, 3, 6, and 12 months post-transplant. Additional samples were sent from bronchoscopy, sputum, and nasopharyngeal washes when clinically indicated. CARV pneumonia was defined as a positive viral test with symptoms and a consistent radiographic infiltrate. Graft death was defined as patient death or re-transplant. BOS was defined according to International Society for Heart and Lung Transplantation (ISHLT) guidelines. We used multivariate Cox modeling to assess the relationship between CARV infection and outcomes. Results: Of 563 total patients, 139 produced 324 positive specimens in 245 episodes of viral infection (repeat samples within 30 days were excluded). The most frequently isolated viruses were coxsackie/echovirus (20.4%), rhinovirus/enterovirus (19.2%), parainfluenza (18.4%), coronavirus (14.3%), and human metapneumovirus (8.2%). The overall risk of CLAD was elevated
with any CARV infection (HR 1.79, p < 0.01), though when analyzed as parallel predictors in subgroup analysis, only clinical pneumonia remained statistically significant (HR 1.64, p = 0.03). Asymptomatic viral infection (HR 1.50, p = 0.08) and symptomatic viral infection (HR 1.03, p = 0.91) did not meet statistical significance. Viral pneumonia significantly increased the risk of graft death (HR 2.58, p < 0.01). However, overall CARV infection (HR 0.92, p = 0.60), asymptomatic CARV infection (HR 0.76, p = 0.24), and symptomatic CARV infection (HR 0.78, p = 0.42) did not. Conclusion: Viral pneumonia increases the risk of graft death and CLAD after lung transplantation. Overall CARV infections also appear to increase the risk of CLAD, although in our cohort this risk was primarily driven by those with viral pneumonia. Asymptomatic viral carriage and symptomatic CARV infection without pneumonia did not appear to impact graft survival. 8( 40) Everolimus and Valganciclovir Prophylaxis: How to Chase CMV But Not the Patient: Insights From PROTECT Randomized Study B. Perciaccante,1 G. Bianchi,1 L. Potena ,1 P. Prestinenzi,1 A. Chiereghin,2 T. Lazzarotto,2 M. Masetti,1 C. Rapezzi,1 G. Magnani,1 F. Grigioni.1 1Heart and Lung Transplant Program, University of Bologna, Bologna, Italy; 2Microbiology Department, University of Bologna, Bologna, Italy. Purpose: Cytomegalovirus (CMV) infection may influence the development of Cardiac Allograft Vasculopathy (CAV). In this prospective randomized study we aimed to analyze the interplay of immunosuppressive, anti-CMV strategies and CMV immunity on the risk for CMV infection and CAV during the first year after transplant. Methods: By a 2x2 randomization process, CMV seropositive heart transplant (HT) recipients were randomized to receive 3 months of valganciclovir prophylaxis (PRO) or a pre-emptive based approach (PRE), and to receive mycophenolate (MMF) or everolimus (EVE) on top of a cyclosporine-based immunosuppressive therapy. All were monitored for CMV infection by whole blood PCR and CMV-immunity reconstitution by elispot assay. At month 1 and 12 after transplant eligible patients underwent intravascular ultrasound (IVUS). Occurrence of CMV infection and change in maximal intimal thickness (MIT) > 0.5mm were study endpoints. Results: Forty-six patients were randomized: 22 to PRE vs. 24 to PRO, and 24 to EVE vs. 22 to MMF. Six (25%) patients discontinued EVE and 13 (54%) did not completed the 3-months period of PRO for adverse events (mainly effusions in EVE and leucopenia in PRO). Only 23 patients underwent IVUS both at month 1 and month 12. After adjusting for donor serology, PRO and EVE were associated with reduced risk of 70 and 54% respectively for CMV infection in the intention to treat (ITT) analysis (P< 0.05). However, EVE discontinuation and lack of PRO completion were associated with increased risk for CMV infection. Only 4 (17%) patients developed the MIT endpoint, not allowing any conclusion about treatments efficacy. Nevertheless 100% of the patients who discontinued EVE developed the MIT endpoint. Recovery of CMV immunity at month 1 by Elispot analysis allowed stratifying the risk for CMV infection: patients with lack of immunity were at higher risk of infection, and most likely to benefit from PRO or EVE (P< 0.01). Conclusion: EVE and PRO are protective from CMV infection, but a significant percentage of patients discontinued the treatments for intolerance and appear to be exposed to higher risk of events. Analysis of CMV immunity recovery may provide guidance in customizing therapeutic strategies, by identifying patients in whom aggressive anti-CMV strategies may have a favorable risk/benefit ratio. 8( 41) Hepatitis B Vaccination in Heart Transplant Recipients: Response Rate and Risk Factors for Loss of Immunity E.S. Sukerman ,1 I. Echenique,2 M. Angarone,1 R. Gordon,3 A. Anderson,3 J. Rich,3 A. Sauer,3 T. Abicht,4 V. Stosor.1 1Infectious Diseases, Northwestern University, Chicago, IL; 2Infectious Diseases, Cleveland Clinic, Weston, FL; 3Cardiology, Northwestern University, Chicago, IL; 4Cardiac Surgery, Northwestern University, Chicago, IL. Purpose: To examine pre-heart transplant (HT) hepatitis B virus (HB) immunization completion and response rates and identify risk factors for loss of HB immunity after HT.