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Antifungal Prophylaxis in Lung Transplant Recipients: A Network Meta-Analysis
S314
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019 CMV infection were seronegative recipients who received a lung from a CMV seropositive donor. Comparison of characteristics and clinical outcomes between resistant CMV patients and control patients is provided in Table 1. No differences in immunosuppression, acute rejection, or pre-transplant sensitization were seen between groups. The peak CMV viral load and duration of CMV viremia were significantly higher in the resistant group. The resistant group had a significantly increased overall mortality after onset of viremia compared to the controls. Conclusion: We conclude that drug resistant CMV infection is rare but patients who develop it have decreased overall survival. Risk factors for developing resistant CMV infection were peak CMV viral load and duration of CMV viremia.
Methods: We retrospectively evaluated the incidence of KS and HHV8 associated lymphoproliferative disorders among all lung transplant recipients at our centre, from January 2008 to December 2017. Clinical data of these patients were collected, taking into account time of onset, donor/ recipient HHV8 serology, treatments and outcomes. Results: Four out of 203 (2%) patients developed KS (Table 1). Disseminated forms of KS occurred through HHV8 infection from a seropositive donor (D+/R-); both patients initially complained of aspecific symptoms (fever and malaise) and presented with pancytopenia and very high HHV8 DNAemia. We observed a very aggressive progression of KS, and patient 3 died 4 weeks after the fourth dose of liposomal doxorubicin due to an untreatable mycotic infection. By contrast, KS due to viral reactivation (i.e., D-/R+) was milder, limited to the skin and responded to modifications in the immunosuppressive regimens. Interestingly, the recipient of the liver harvested from patient 4’s donor developed another serious HHV8 related disease (i.e., Castelman’s disease, investigation currently ongoing at another transplant centre). Conclusion: We suggest implementation of D/R serological screening for HHV-8 before transplantation, in order to identify patients at risk of developing HHV-8 related diseases, improve clinical and virological surveillance and possibly individualize immune-suppressive therapy. For the time being, in the absence of a systematic screening, we strongly recommend to report index cases as soon as possible to regional allocation systems in order to identy other recipients potentially at risk.
782 781 Drug Resistant CMV Infection in Lung Transplantation Patients: Incidence, Characteristics and Clinical Outcomes E. Heli€ovaara, S. Husain, T. Martinu, L. Singer, M. Cypel, A. Humar, S. Keshavjee and J. Tikkanen. University Health Network, Toronto, ON, Canada.
Antifungal Prophylaxis in Lung Transplant Recipients: A Network MetaAnalysis S. Herrera,1 F. Foroutan,2 and S. Husain.1 1Multi Organ Transplant Unit, Division of Infectious Diseases, University Health Network, Toronto, ON, Canada; and the 2Ted Rogers Center of Excellence in Heart Function, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
Purpose: Cytomegalovirus (CMV) infection and development of CMV drug resistance can cause significant morbidity and mortality in lung transplantation (LTX) patients. We investigated the incidence of CMV drug resistance in adult LTX patients and characterized this patient group and its outcomes. Methods: We analyzed a single center retrospective cohort of LTX patients who had undergone CMV UL97 and UL54 genotyping for clinically suspected drug resistance. Of the 852 patients who received LTX between January 2012 and May 2018, 27 patients were genotyped, and 11 were confirmed to have drug resistance. Case-matched controls (3 control patients for each resistant patient) were identified by matching for CMV serostatus, development of CMV disease or significant CMV viremia (over 3000 IU/ ml), and transplantation date. Results: The cumulative incidence of drug resistant CMV was 1.29% (11/852). Altogether 27 patients were tested for drug resistance and 40.7% (11/27) of strains were resistant, 29.6% (8/27) sensitive, and 29.6% (8/27) inconclusive. The median follow-up time was 630 days (range 100-1950 days). Most patients (7/10) who developed resistant
Purpose: Invasive fungal infections (IFIs), in particular invasive aspergillosis cause significant morbidity and mortality in lung transplant recipients (LTRs). Various antifungal agents are used either for universal or preemptive/ targeted prophylaxis. However, as there is a lack of randomized control studies, the best agent for prophylaxis/ pre-emptive treatment remains unknown. Methods: We identified studies comparing regimens for antifungal prophylaxis in LTRs. We ran a frequentist network (Figure 1). We checked for inconsistency in the network. We could not reject the null hypothesis that the model was consistent between the direct and indirect estimates. Therefore, the model was run under the consistency assumption. Results: Ten observational studies were included, which reported comparisons of liposomal amphotericin B (L-AmB), itraconazole, voriconazole, isavuconazole and no treatment. Amphotericin B was the best agent for reducing the rate of IFI in the network meta-analysis, followed by isavuconazole and voriconazole respectively (Table 1). Conclusion: Our network analysis suggests that L-AmB and isavuconazole are the preferred antifungal agents for reducing IFI in LTRs.
Abstracts
S315 incidence of approximately 12% in the literature. Median time to development of IMI occurred later than 3 months; thus patients with mold colonizations prior to transplant may warrant longer durations of systemic prophylaxis.
Matrix showing relative effects of each treatment on the odds of IA in a mixed treatment comparison Liposomal amphotericin B Liposomal amphotericin
Voriconazole
Itraconazole
Isavuconazole
No treatment
3.62 (0.42
6.63 (0.65
2.14 (0.08
9.00 (1.84
- 31.32)
- 67.65)
- 60.62)
- 43.94)
B Voriconazole
0.28 (0.03
1.83 (0.38
0.59 (0.05
- 2.39)
- 8.88)
- 7.60)
Itraconazole
0.15 (0.01 - 1.54)
- 2.64)
Isavuconazole
0.47 (0.02
1.69 (0.13
No treatment
0.11 (0.02
- 13.18) - 0.54)
0.55 (0.11
- 21.63) 0.40 (0.07 - 2.31)
0.32 (0.02 to 6.49) 3.09 (0.15 -
4.68)
14.32) 1.36 (0.21 8.60) 4.20 (0.19 -
62.09) 0.74 (0.12 -
2.49 (0.43 -
92.56) 0.24 (0.01 - 5.26)
783 Analysis of Risk Factors for Invasive Mold Infections in Lung Transplant Recipients J. Sullivan,1 N. Sharma,2 K. Patel,2 and A. Logan.2 1Jackson Memorial Hospital, Miami, FL; and the 2Tampa General Hospital, Tampa, FL. Purpose: The purpose of this study is to identify risk factors associated with the development of IMI compared to mold colonization. Methods: A single-center, retrospective chart review was conducted on patients who received a lung transplant (LTr) between January 2012 and January 2016. Patients colonized with molds or who had IMI at any point were included for comparison of risk factors and outcomes. Targeted antifungal prophylaxis with voriconazole for 3 months was initiated for patients colonized before transplant or those who had positive donor cultures. Results: A total of 150 patients were transplanted within the time period and 94 met inclusion criteria; 81 (54%) were colonized and 13 (8.7%) had IMI. IMI were more common in males; 65% vs 23%, p<0.01 and factors associated with development of IMI included intra-abdominal surgery after transplant (25.9% vs. 53.9%, p=0.04), colonization at index hospitalization (19.8% vs. 53.9%, p < 0.01), return to the OR within 72 hours of transplant (6.2% vs. 30.8%, p=0.02), and use of TPN after transplant (18.5% vs. 46.2%, p=0.03). The median time to development of mold colonization or IMI was 108 days compared to 237 days respectively (p=0.01). There was no difference in secondary outcomes including rejection and mortality. Conclusion: A relatively low incidence of IMI developed even with the conservative approach of targeted prophylaxis compared to the reported
784 Lung Transplantation for Patients with Cystic Fibrosis and Achromobacter xylosoxidans in the Lung Allocation Score Era E. Nolley,1 K. Robinson,1 J. Pilewski,1 P. Sanchez,2 J. D'Cunha,2 and M. Morrell.1 1Pulmonary Allergy and Critical Care, University of Pittsburgh, Pittsburgh, PA; and the 2Division of Lung Transplantation and Lung Failure, University of Pittsburgh, Pittsburgh, PA. Purpose: Lung transplantation is an accepted therapy for patients with end stage lung disease due to Cystic Fibrosis (CF). Up to ten percent of patients with CF are colonized with Achromobacter xylosoxidans, a gram negative organism that due to its intrinsic resistance to many antibiotics may affect negatively impact post-transplant outcomes. Methods: We conducted a retrospective cohort analysis of all patients receiving lung transplantation for CF from 6/2005-2015 at the University of Pittsburgh Medical Center. Patients with Burkholderia species were excluded. General and transplant related demographics, pre and post-transplant respiratory cultures, and cause of death were examined. Graft survival was measured through February 2018 or last follow-up. Descriptive statistics were used to compare baseline demographics using parametric and non-parametric tests. Survival was estimated and compared by Kaplan Meier analysis. Results: Twenty-nine percent (26/89) of patients had a history of Achromobacter infection prior to transplantation. Pre-transplantation, patients with Achromobacter had a slightly higher FEV1 (25.8 +/- 2.1 vs 22.3 +/0.07, p=0.031) but trended towards requiring more mechanical ventilation (42 vs 24%, p=0.081). Compared to patients without Achromobacter, there was not a statistically significant difference in 1 year (0.84 vs 0.94%) and
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019 CMV infection were seronegative recipients who received a lung from a CMV seropositive donor. Comparison of characteristics and clinical outcomes between resistant CMV patients and control patients is provided in Table 1. No differences in immunosuppression, acute rejection, or pre-transplant sensitization were seen between groups. The peak CMV viral load and duration of CMV viremia were significantly higher in the resistant group. The resistant group had a significantly increased overall mortality after onset of viremia compared to the controls. Conclusion: We conclude that drug resistant CMV infection is rare but patients who develop it have decreased overall survival. Risk factors for developing resistant CMV infection were peak CMV viral load and duration of CMV viremia.
Methods: We retrospectively evaluated the incidence of KS and HHV8 associated lymphoproliferative disorders among all lung transplant recipients at our centre, from January 2008 to December 2017. Clinical data of these patients were collected, taking into account time of onset, donor/ recipient HHV8 serology, treatments and outcomes. Results: Four out of 203 (2%) patients developed KS (Table 1). Disseminated forms of KS occurred through HHV8 infection from a seropositive donor (D+/R-); both patients initially complained of aspecific symptoms (fever and malaise) and presented with pancytopenia and very high HHV8 DNAemia. We observed a very aggressive progression of KS, and patient 3 died 4 weeks after the fourth dose of liposomal doxorubicin due to an untreatable mycotic infection. By contrast, KS due to viral reactivation (i.e., D-/R+) was milder, limited to the skin and responded to modifications in the immunosuppressive regimens. Interestingly, the recipient of the liver harvested from patient 4’s donor developed another serious HHV8 related disease (i.e., Castelman’s disease, investigation currently ongoing at another transplant centre). Conclusion: We suggest implementation of D/R serological screening for HHV-8 before transplantation, in order to identify patients at risk of developing HHV-8 related diseases, improve clinical and virological surveillance and possibly individualize immune-suppressive therapy. For the time being, in the absence of a systematic screening, we strongly recommend to report index cases as soon as possible to regional allocation systems in order to identy other recipients potentially at risk.
782 781 Drug Resistant CMV Infection in Lung Transplantation Patients: Incidence, Characteristics and Clinical Outcomes E. Heli€ovaara, S. Husain, T. Martinu, L. Singer, M. Cypel, A. Humar, S. Keshavjee and J. Tikkanen. University Health Network, Toronto, ON, Canada.
Antifungal Prophylaxis in Lung Transplant Recipients: A Network MetaAnalysis S. Herrera,1 F. Foroutan,2 and S. Husain.1 1Multi Organ Transplant Unit, Division of Infectious Diseases, University Health Network, Toronto, ON, Canada; and the 2Ted Rogers Center of Excellence in Heart Function, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
Purpose: Cytomegalovirus (CMV) infection and development of CMV drug resistance can cause significant morbidity and mortality in lung transplantation (LTX) patients. We investigated the incidence of CMV drug resistance in adult LTX patients and characterized this patient group and its outcomes. Methods: We analyzed a single center retrospective cohort of LTX patients who had undergone CMV UL97 and UL54 genotyping for clinically suspected drug resistance. Of the 852 patients who received LTX between January 2012 and May 2018, 27 patients were genotyped, and 11 were confirmed to have drug resistance. Case-matched controls (3 control patients for each resistant patient) were identified by matching for CMV serostatus, development of CMV disease or significant CMV viremia (over 3000 IU/ ml), and transplantation date. Results: The cumulative incidence of drug resistant CMV was 1.29% (11/852). Altogether 27 patients were tested for drug resistance and 40.7% (11/27) of strains were resistant, 29.6% (8/27) sensitive, and 29.6% (8/27) inconclusive. The median follow-up time was 630 days (range 100-1950 days). Most patients (7/10) who developed resistant
Purpose: Invasive fungal infections (IFIs), in particular invasive aspergillosis cause significant morbidity and mortality in lung transplant recipients (LTRs). Various antifungal agents are used either for universal or preemptive/ targeted prophylaxis. However, as there is a lack of randomized control studies, the best agent for prophylaxis/ pre-emptive treatment remains unknown. Methods: We identified studies comparing regimens for antifungal prophylaxis in LTRs. We ran a frequentist network (Figure 1). We checked for inconsistency in the network. We could not reject the null hypothesis that the model was consistent between the direct and indirect estimates. Therefore, the model was run under the consistency assumption. Results: Ten observational studies were included, which reported comparisons of liposomal amphotericin B (L-AmB), itraconazole, voriconazole, isavuconazole and no treatment. Amphotericin B was the best agent for reducing the rate of IFI in the network meta-analysis, followed by isavuconazole and voriconazole respectively (Table 1). Conclusion: Our network analysis suggests that L-AmB and isavuconazole are the preferred antifungal agents for reducing IFI in LTRs.
Abstracts
S315 incidence of approximately 12% in the literature. Median time to development of IMI occurred later than 3 months; thus patients with mold colonizations prior to transplant may warrant longer durations of systemic prophylaxis.
Matrix showing relative effects of each treatment on the odds of IA in a mixed treatment comparison Liposomal amphotericin B Liposomal amphotericin
Voriconazole
Itraconazole
Isavuconazole
No treatment
3.62 (0.42
6.63 (0.65
2.14 (0.08
9.00 (1.84
- 31.32)
- 67.65)
- 60.62)
- 43.94)
B Voriconazole
0.28 (0.03
1.83 (0.38
0.59 (0.05
- 2.39)
- 8.88)
- 7.60)
Itraconazole
0.15 (0.01 - 1.54)
- 2.64)
Isavuconazole
0.47 (0.02
1.69 (0.13
No treatment
0.11 (0.02
- 13.18) - 0.54)
0.55 (0.11
- 21.63) 0.40 (0.07 - 2.31)
0.32 (0.02 to 6.49) 3.09 (0.15 -
4.68)
14.32) 1.36 (0.21 8.60) 4.20 (0.19 -
62.09) 0.74 (0.12 -
2.49 (0.43 -
92.56) 0.24 (0.01 - 5.26)
783 Analysis of Risk Factors for Invasive Mold Infections in Lung Transplant Recipients J. Sullivan,1 N. Sharma,2 K. Patel,2 and A. Logan.2 1Jackson Memorial Hospital, Miami, FL; and the 2Tampa General Hospital, Tampa, FL. Purpose: The purpose of this study is to identify risk factors associated with the development of IMI compared to mold colonization. Methods: A single-center, retrospective chart review was conducted on patients who received a lung transplant (LTr) between January 2012 and January 2016. Patients colonized with molds or who had IMI at any point were included for comparison of risk factors and outcomes. Targeted antifungal prophylaxis with voriconazole for 3 months was initiated for patients colonized before transplant or those who had positive donor cultures. Results: A total of 150 patients were transplanted within the time period and 94 met inclusion criteria; 81 (54%) were colonized and 13 (8.7%) had IMI. IMI were more common in males; 65% vs 23%, p<0.01 and factors associated with development of IMI included intra-abdominal surgery after transplant (25.9% vs. 53.9%, p=0.04), colonization at index hospitalization (19.8% vs. 53.9%, p < 0.01), return to the OR within 72 hours of transplant (6.2% vs. 30.8%, p=0.02), and use of TPN after transplant (18.5% vs. 46.2%, p=0.03). The median time to development of mold colonization or IMI was 108 days compared to 237 days respectively (p=0.01). There was no difference in secondary outcomes including rejection and mortality. Conclusion: A relatively low incidence of IMI developed even with the conservative approach of targeted prophylaxis compared to the reported
784 Lung Transplantation for Patients with Cystic Fibrosis and Achromobacter xylosoxidans in the Lung Allocation Score Era E. Nolley,1 K. Robinson,1 J. Pilewski,1 P. Sanchez,2 J. D'Cunha,2 and M. Morrell.1 1Pulmonary Allergy and Critical Care, University of Pittsburgh, Pittsburgh, PA; and the 2Division of Lung Transplantation and Lung Failure, University of Pittsburgh, Pittsburgh, PA. Purpose: Lung transplantation is an accepted therapy for patients with end stage lung disease due to Cystic Fibrosis (CF). Up to ten percent of patients with CF are colonized with Achromobacter xylosoxidans, a gram negative organism that due to its intrinsic resistance to many antibiotics may affect negatively impact post-transplant outcomes. Methods: We conducted a retrospective cohort analysis of all patients receiving lung transplantation for CF from 6/2005-2015 at the University of Pittsburgh Medical Center. Patients with Burkholderia species were excluded. General and transplant related demographics, pre and post-transplant respiratory cultures, and cause of death were examined. Graft survival was measured through February 2018 or last follow-up. Descriptive statistics were used to compare baseline demographics using parametric and non-parametric tests. Survival was estimated and compared by Kaplan Meier analysis. Results: Twenty-nine percent (26/89) of patients had a history of Achromobacter infection prior to transplantation. Pre-transplantation, patients with Achromobacter had a slightly higher FEV1 (25.8 +/- 2.1 vs 22.3 +/0.07, p=0.031) but trended towards requiring more mechanical ventilation (42 vs 24%, p=0.081). Compared to patients without Achromobacter, there was not a statistically significant difference in 1 year (0.84 vs 0.94%) and