Donors with Bacterial Meningitis: Outcomes in Lung Transplant Recipients

Donors with Bacterial Meningitis: Outcomes in Lung Transplant Recipients

Abstracts S321 organisms detected with MSSA included GNB (n= 5) and Candida (n= 1). Reflecting the efficacy of targeted antibiotic therapy, the only d...

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Abstracts S321 organisms detected with MSSA included GNB (n= 5) and Candida (n= 1). Reflecting the efficacy of targeted antibiotic therapy, the only donor derived organism cultured after POD 1 was Aspergillus and the only pre-LTX organism was P. aeruginosa (1 patient each). Indication for transplant did not appear to be a determinate of early bacterial detection. Conclusion: Antimicrobial therapy targeted to known and donor detected organisms appears effective in modulating early microbial infection after LTX as assessed by prospective surveillance of lower respiratory tract (LRT) microbial load using BAL. The impact on other components of the human respiratory microbiome, not reported here, remains to be established. Our longitudinal study holds promise of elucidating long-term outcomes associated with the dynamics of the LRT microbiome after LTX. 9( 87) Clinical Assessment of Cytomegalovirus Specific Cell Mediated Immunity in a Prospective Cohort of Lung Transplant Recipients S.V. Campos ,1 M.N. Samano,2 P.M. Pego-Fernandes,2 R.O. Teixeira,1 R.M. Carraro,1 J.E. Afonso-Junior,1 A.N. Costa,1 C.M. Machado,3 A.C. Souza,3 B.B. Pereira,3 L.M. Fernandes,2 L. Abdalla.2  1Pneumology, Heart Institute of Sao Paulo Medical School, Sao Paulo, Brazil; 2Thoracic Surgery, Heart Institute of Sao Paulo Medical School, Sao Paulo, Brazil; 3Virology Laboratory (LIM 52-HCFMUSP), Institute of Tropical Medicine of Sao Paulo Medical School, Sao Paulo, Brazil. Purpose: Cytomegalovirus (CMV) specific CD8T cell mediated immunity assays have been used to individualize risks of infection and antiviral prophylaxis among solid organ transplant patients. In our brazilian lung transplant (LTx) center, intravenous Ganciclovir is still been used as a non daily, non ideal, prophylaxis due to costs. In this study, we aimed to evaluate the usefulness of the secretion of interferon-gama by CMV-specific CD8T cells to determine the risk of CMV infection or disease and to opitimize resources for antiviral prophylaxis after LTx. Methods: These are partial data of an ongoing study of a prospective observational cohort of LTx recipients under intravenous Ganciclovir 3 times per week for 3 months after LTx. QuantiFERON CMV (QTF) test was performed at surveillance bronchoscopy times: 2 and 6 weeks post-LTx and 3, 6, 9 and 12 months post-LTx. The primary outcome was CMV infection or disease. Results: Until now, 32 patients were included and 71 QTF results were available for analysis (table 1). Five patients (15%) presented CMV events (2 pneumonitis, 1 gastritis and 2 CMV syndrome). Two were on Ganciclovir profilaxis when CMV occured and both had non reactive QTF results. Two had reactive QTF but had a treated rejection episode before CMV disease. The last patient with CMV syndrome had all QTF results, since LTX, non reactive. Conclusion: We observed a dynamic reconstitution of antiviral cellular immunity following LTx with increased number of reactive QTF results during ganciclovir prophylaxis. A correlation between non reactive QTF results and CMV infection episodes was also observed. We believe that, at the end of this study, we will be able to identify the increased risk groups for CMV infection and thus optimize use and costs of antiviral prophylaxis.

QTF-CMV results over time after LTx

QTF CMV results

Time after LTx

6 3 6 9 12 2 weeks weeks months months months months

Reactive

7

12

14

10

1

0

Non reactive Indeterminate Total

1 12 20

4 4 20

3 1 18

2 0 12

0 0 1

0 0 0

9( 88) A Prophylaxis-Free, Pre-Emptive Approach to the Management of CMV After Lung Transplantation: Single Center Results A. Bertani ,1 P. Vitulo,2 A. Mularoni,3 P. Grossi,3 L. De Monte,1 E. Russo,1 M. Beretta,2 L. Martino,2 A. Callari.2  1Thoracic Surgery and Lung Transplantation, IRCCS ISMETT- UPMC Italy, Palermo, Italy; 2Pulmonology, IRCCS ISMETT- UPMC Italy, Palermo, Italy; 3Infectious Diseases, IRCCS ISMETT- UPMC Italy, Palermo, Italy.

Purpose: The results of a single-center experience with the management of Cytomegalovirus (CMV) after lung transplantation using a prophylaxis-free, pre-emptive strategy are retrospectively reviewed. Methods: 140 consecutive patients who received lung transplantation between June 2006 and September 2016 were included in the cohort. In all patients, CMV-DNA peripheral replication was monitored weekly for the first three months, monthly for the first year post-transplant, and every three months thereafter. No routine prophylaxis was given independently from the serological status. Immunosuppression was based on tacrolimus, MMF and low dose steroids. An antiviral treatment was initiated in patients with greater than 100,000 CMV-DNA peripheral copies/mL using i.v. gancyclovir or p.o. valgancyclovir. The antiviral treatment was continued until two consecutive negative CMV-DNA samples were obtained at weekly intervals. Patients with < 100,000 CMV peripheral copies received an antiviral treatment only in case of concurrent steroid therapy for acute rejection events. The aim of the study was to assess the occurrence and morbidity of CMV disease. Results: The mean follow-up time was 3.6 years. 99 patients (70.7%) showed active replication of CMV during the follow-up period with 29 (20.7%) patients reaching the predefined threshold (> 100,000 copies/mL) necessitating antiviral treatment. Overall, 39 patients (27.8%) received antiviral treatment for CMV. Out of 872 viral load measurements showing active CMV replication, 60 (6.9%) samples exceeded the predefined threshold warranting antiviral treatment. The median duration of the antiviral treatment was 35.0 days. CMV disease, defined as the histological evidence of the virus at an organ site, occurred in 7 patients (4.9%). No patients died for CMV as the primary cause of death. Conclusion: While most patients showed some degree of CMV replication, the vast majority of patients maintained low CMV-DNA blood levels without developing clinical disease. Pre-emptive therapy on patients developing > 100,000 copies/mL peripheral viral replication allowed an effective control of CMV DNA-emia and maintaining a low occurrence of CMV disease. Long term follow-up of this cohort is required to assess the impact of this approach on the development of BOS.

9( 89) Donors with Bacterial Meningitis: Outcomes in Lung Transplant Recipients H. Grewal ,1 M. Budev.2  1Cleveland Clinic Foundation, Parma, OH; 2Cleveland Clinic Foundation, Cleveland, OH. Purpose: Lung transplant remains the definitive treatment for many end stage lung diseases. Limited organ availability remains a major contributor to waitlist mortality with a rate of 10.4 per 100 waitlist years. Only 20% of the available organs are considered suitable and utilized for lung transplantation. Successful lung transplantation has been reported from donors infected with bacterial or fungal organisms. Data involving increased risk donors is limited to case reports and single center case series. The purpose of this study was to assess the outcomes of lung transplantation from donors with bacterial meningitis as a cause of deaths. Methods: Between January 1998 and December 2014, we identified adult patients by retrospective chart review at the Cleveland Clinic Foundation who underwent lung transplantation from donors with bacterial meningitis. Post-transplantation outcomes including graft dysfunction, and infectious complications were reviewed. Results: Eleven recipients (Female =  8) were identified as having received organs from donors with bacterial meningitis. Bacteria identified in donors included Streptococcus pneumoniae and Neisseria meningitides. All recipients received antibiotics during the pre and post-transplantation period as per protocol. One patient received induction with ATG. All recipients remained free of infectious complications in the post-operative period. Severe graft dysfunction was not present at time 72 hours. Survival at 1, 3 and 5 years’ post-transplant was 91%, 60% and 60% respectively. One recipient died in the first year due to post transplant graft dysfunction with chronic ventilator dependence and failure to thrive which was unrelated to the donor status. Conclusion: In our study lung transplantation from increased risk donors with bacterial meningitis, was not associated with an increased risk of infectious complications in recipients. In the setting of scarce organ availability increased risk donors with bacterial meningitis should be considered for lung donation.

S322

The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017

Table 1

Patient Disease

Age/Sex LAS

IS

Survival Time Transplant  PGDT= 72hrs (Months)

1 2 3 4 5 6 7 8 9 10 11

51/F 50/F 40/F 50/M 68/F 63/M 68/M 66/F 65/F 65/F 47/F

Aza Aza, Cyc Cyc, MMF Tac Tac Tac, MMF Tac Tac, MMF Tac, MMF Tac, MMF Tac

R D D D L + BAR L R R L R D

A1AT COPD CF COPD COPD IPF CPFE IPF IPF IPF Sarcoidosis

30.71 31.61 72.77 42.46 79.65 37.59 37.19 37.25

1 2 0 1 1 0 0 1

29* 202 128* 3* 86 24 12* 13* 75 75 45

9( 90) Acute Rejection Interaction with Viral Pneumonia Augments CLAD Risk A.L. Gregson , J. Grotts, M. Shino, S.S. Weigt, J. Belperio.  UCLA, Los Angeles, CA. Purpose: Our recent transcriptional analysis of exosomes during acute rejection demonstrated a significant innate inflammatory response at the time of acute rejection. We have also shown that that viral pneumonia is a significant clinical risk factor for CLAD. This led us to believe that there might be an important interaction between acute rejection and viral pneumonia if they were to occur in close temporal proximity. Methods: Using a cohort of 563 lung transplant recipients at our institution we examined more closely the possibility of an interaction between acute rejection and viral pneumonia. A survival model of time to CLAD with time varying covariates for bacterial infection, viral pneumonia and acute rejection was developed. An indicator variable was created to denote whether viral infection and acute rejection occurred within 30 days of one another. A stepwise algorithm used AIC to select variables to include in a 30-day interaction model. Results: Acute rejection was significantly associated with future development of CLAD (HR 1.21 [1.1-1.3], p=  0.004) and viral pneumonia itself in this model was of borderline significance (HR 1.36 [0.9-1.8], p= 0.20). In the 30-day interaction model viral pneumonia within 30 days of acute rejection was a risk factor for future CLAD (HR 4.14 [2.9-5.3], p= 0.04). Conclusion: In this model viral pneumonia occurring within 30 days of acute rejection augmented the risk of CLAD. This suggests that innate inflammatory responses such as viral pneumonia may potentiate alloimmune responses and increase the risk of CLAD beyond the effect of each covariate independently. 9( 91) Management of Pseudomonas aeruginosa Infection After Lung Transplantation Across the UK and the Impact on Long-Term Survival T.C. Gan ,1 A.E. Cockburn,2 H. Yung,3 E. Karimi,4 L. Dirmantaite,5 M. Khan,6 A. Perry,2 R. Gell,5 M. Al-Aloul,4 R.D. Thompson,7 J. Parmar,3 M. Carby,5 A.J. Fisher,2 O. Association of Lung Transplant Physicians UK.2  1Pulmonary Diseases, Tuberculosis and Lung Transplantation, University Medical Center Groningen, Groningen, Netherlands; 2Cardiopulmonary Transplantation Unit, Freeman Hospital, Newcastle, United Kingdom; 3Lung Transplantation Unit, Papworth Hospital, Cambridge, United Kingdom; 4Lung Transplantation Unit, University Hospital South Manchester, Manchester, United Kingdom; 5Lung Transplantation Unit, Royal Brompton and Harefield, Middlesex, United Kingdom; 6Respiratory Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; 7Lung Transplantation Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. Purpose: Pseudomonas aeruginosa (Pa) infection after lung transplantation (Ltx) is associated with increased risk of chronic lung allograft dysfunction

yet its impact on long-term survival is unknown. The management of Pa infection and its consequences for survival was investigated in a multi-centre retrospective cohort. Methods: Recipients of single, bilateral or heart-lung transplant in 5 UK centres were included. Time to the first Pa isolation, treatment and overall survival were assessed in the whole cohort and stratified by cystic fibrosis (CF) and non-CF pre-transplant diagnoses. Mann-Whitney U-test, KaplanMeier and Wilcoxon rank-test were used for analyses. Results: A total of 836 recipients (121 single, 696 bilateral and 19 heartLtx) transplanted between 2009-2013 were included, 224/836 had CF. Predominant non-CF diagnoses were COPD (n= 275) and pulmonary fibrosis (n= 152). Pa was isolated in 346/836 recipients, 158 CF and 188 non-CF. In the CF-group 136/158 had persistent (reoccurrence of pre-transplant Pa) and 22/158 de novo Pa. In the non-CF group 38/188 had persistent and 150/188 de novo Pa. In CF with persistent Pa 101/136 were treated and 35/136 not. In non-CF with de novo Pa 80/150 received treatment while 70/150 did not. Time to first Pa culture was shorter in CF than non-CF [median(range) 14 (0-2792) vs. 65 (0-2341) days, p<  0.001]. At 1 year, 38% CF and 76% nonCF were free of Pa (p< 0.001). Overall 271/836 recipients received anti-Pa therapies. Antibiotic inhalation was the commonest therapy; 156 Colistin neb; 45 Taurolin neb (broad spectrum anti-microbial); 16 Tobramycin neb and 3 Colobreath® inhaler. Forty recipients had intravenous antibiotics initially followed by inhaled therapy. CF recipients had better overall survival than non-CF, p =  0.047. There was no effect of presence or type of Pa infection (persistent or de novo) on survival. In CF with persistent Pa, survival was better with treatment than without, p<  0.01. In non-CF with de novo Pa survival was not different between treated or non-treated recipients. Conclusion: Pa infection is more common in CF than non-CF recipients where time to first positive culture is shorter. Nebulised antibiotics are the commonest management approach. In this univariate analysis treatment of CF recipients with persistent Pa may offer a survival advantage compared to non-treated CF recipients. 9( 92) Biologically-Inspired Spiral Flow Generation for Mechanically Assisted Circulation C.D. Tkatch ,1 P.S. Huang Zhang,1 W. Fischer,1 H. Eisen,2 J. Yasha Kresh.1  1Cardiothoracic Surgery, Drexel University College of Medicine, Philadelphia, PA; 2Department of Medicine, Drexel University College of Medicine, Philadelphia, PA. Purpose: Mechanical circulatory support (MCS) is increasingly being used for long-term hemodynamic assistance in heart failure patients. MCS devices improve mortality, but create non-physiological flow fields that are maladapted to patient-specific needs. MCS are known to increase wall shear stress (WSS), hemolysis, platelet activation (thrombosis), jet outflow impact-pressure, vessel-wall remodeling and risk for aortic insufficiency (AI). Re-establishment of native spiral hemodynamics may confer several benefits: WSS gradient normalization, organization/entrainment of multidirectional flow streams, and reduction of flow recirculation/stasis regions. The overarching hypothesis is that incorporating spiral hemodynamics into MCS designs will improve device functional patient compatibility. Methods: Computational fluid dynamic (CFD) simulations were used to model the outflow of an idealized cannula. A mock circulatory loop, incorporating a spiral flow inducer (independent axial & circumferential flow control) and hollow glass microspheres (for echo contrast), was constructed to validate the CFD results. Multimodal clinical Doppler ultrasound was used to visualize the complex transverse velocity patterns. The experiments tested for spiral flow preservation (helicity) and dynamic pressure (force impact) of fluid jets. Results: The CFD simulations and mock circulatory loop experiments demonstrated that spiral flow significantly reduced dynamic pressure (impact force) of fluid jets, compared to ‘straightened’ flow. Spiral flow persistence length (peak helicity values) responded linearly to spiral flow content; the threshold for the onset of dissipative (resistive) losses was at > 60% spiral flow content. Conclusion: Spiral outflow can improve MCS performance by attenuating jetting and vascular remodeling, promoting beneficial biomimetic fluid transport and interface. The clinical impact is spiral flow can be instrumental in optimizing MCS hemodynamics, potentially obviating AI.