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Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients (SOT)

Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients (SOT). Our experience with AmBisome. More than 10 years experience in 383 patients. Two double blind placebo controlled randomized trials with AmBisome as prophylaxis

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Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients (SOT)

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  1. Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients(SOT)

  2. Our experience with AmBisome • More than 10 years experience in 383 patients. • Two double blind placebo controlled randomized trials with AmBisome as prophylaxis • Allogeneic & autologous BMT • Liver transplant recipients • Three Retrospective analyses of treatment with respect to safety and efficacy • Allogeneic BMT recipients (5 years) (79 patients) • Solid organ transplant recipients (10years) (196 patients) • Child recipients of transplant (7 years) (61 patients)

  3. Fungal Infections - Morbidity /Mortality Invasive fungal infections contribute to the morbidity and mortality in SOT recipients. • Reported incidence: up to 53 % • Kidney 0 - 20 % • Liver 4 - 42 % • Pancreas 6 - 38 % • Heart/lung 10 - 35 % • Small bowel 33 - 53 % • Reported mortality: up to 77 % for Candidosis up to 100 % for Aspergillosis

  4. Incidence of invasive fungal infections at our center during the time periods 1989 to 1994 & 1996 Organ n V*FI Incid S**FI Incid Liver 240 21 9% 17 16 % Kidney 540 5 1% 16 4 % Kidney & Pancreas 38 1 3% 9 26 % BMT 199 17 9% 41 29 % *VFI = verified fungal infection **SFI = suspected fungal infection

  5. AmBisome prophylaxis Liver transplant recipients Transplantation. 59: 1: 45-50, 1995. Transplant. Proc.27: 1195-1198, 1995.

  6. Study Design LTX prophylaxis • Double blind randomized, placebo controlled study • 86 patients were randomized Prophylactic treatment : • Treatment group : AmBisome, 1 mg/kg daily i.v. • Control group : Equal volume of placebo drug i.v. • Treatment during days 1 to 5 posttransplant Evaluation criteria for efficacy: • 77 patients who recieved all 5 days of prophylaxis

  7. Results Adverse Events LTX prophylaxis all 84 patients

  8. Results invasive fungal infections after prophylaxis in LTX, first year p<0.01 p<0.05

  9. LTX prophylaxis; Results early FI : Placebo group Invasive fungal infections • 5 Candida albicans inf: 4 peritonitis - abdomen cultures 1 fungemia - blood cultures • 1 Aspergillus niger inf: Pneumonia - BAL culture + biopsy • Median day to FI : 12 (range 6 - 20) • All patients recieved treatment and 5 survived

  10. LTX prophylaxis; Results late FI : Placebo group Invasive fungal infections • 4 Candida albicans inf: 1 peritonitis - abdomen cultures 3 disseminated - autopsy findings • 1 Aspergillosis: Disseminated - autopsy finding • Median day to FI : 150 (range 41 - 365) • 2 of 5 patients recieved treatment and 1was cured

  11. LTX prophylaxis; Results late FI : AmBisome group Invasive fungal infections • 3 Aspergillus spp inf: 1 pneumonia – autopsy findings 2 disseminated – autopsy findings • 1 Candida albicans: Cholangitis - cultures • Median day to FI : 81 (range 39 - 325) • 1 of 4 patients recieved treatment and was cured

  12. AmBisome treatment Solid organ transplant recipients, 10 year data

  13. SOT patients • Patients treated between Jan 1989 - March 1999 • 196 solid organ transplant recipients • 220 episodes of AmBisome treatment • 56 for a verified infections • 79 for a suspected infections • 85 as prophylaxis • 106 males • 90 females • Median age was 42 years, range 1 - 72

  14. SOT patients • 123 liver (LTX) transplant recipients • 3 liver and bone marrow transplant recipients • 5 liver and kidney transplant recipients • 42 kidney (KTX) transplant recipients • 21 kidney & pancreas (KPTX) transplant recipients • 1 kidney and insulin islet transplantation recipient • 1 pancreas (P) transplant recipients

  15. AmBisome treatment data in SOT Fungal Infection AmBisome treatment Verified Suspected Prophylactic Duration (days), mean ± SD (median) 23±17(18) 18±15 (14) 16±19 (7) range 4-81 1-80 1-83 Max. dose (mg), mean ± SD (median) 2.0±1 (1.8) 1.7±0.9 (1.4) 1.4±0.8 (1.0 ) range 0.7-5.5 0.7-5 0.6-6 Total dose (g), mean ± SD (median) 1.7±1.7 (0.95) 1.4±1.3 (1.1) 0.6±0.5 (0.4) range 0.05-8.1 0.06-8 0.03-2.4

  16. Days with AmBisome

  17. AmBisome dose(mg/kg/d)

  18. Total dose AmBisome (gram)

  19. Adverse events in SOT • 335 adverse events were reported • 9 (3%) were regarded as caused by AmBisome treatment • 6 Lumbago • 2 Lumbago combined with chills • 1 Lumbago with dyspnea • No anaphylactic reaction was reported • 224 (67%) of the adverse events were regarded as probably related to AmBisome • 112 (33%) of the adverse events were regarded as not related to AmBisome

  20. Kidney function before, during and after AmBisome treatment measured as S-creatinine

  21. Efficacy; Suspected FI in SOT • 75 patients recieved 79 episodes of treatment for suspected FI • 57 patients survived with clearance of symptoms and 10 died with no FI at autopsy • 7 patients died, no autopsy was performed • 1 patient died with FI at autopsy (Aspergillus. fum) • Efficacy was shown in 67 out of 75 patients, 89 %

  22. Proven invasive fungal infections in SOT • A total of 56 proven infections were treated in 50 patients • 38 LTX, 7 KTX and 5 KPTX recipients • 20 cholangitis (18 C. alb, 1 C. parapsilosis & 1 C. glabrata) • 14 perotonitis (13 C. albicans & 1 C. pelliculosa ) • 14 fungemias (13 C. albicans & 1 C. glabrata) • 4 pneumonias (2 Asp. sp, 1 C. alb + glab, 1 C. alb.) • 3 disseminated inf. (C. alb.) • 1 urinary tract infection (C. alb)

  23. Efficacy, proven invasive fungal infections in SOT • Out of 50 patients with proven infections; • 14 patients died • 10 were FI negative at autopsy • 3 was positive for fungi at autopsy • 1 was not autopsied • Survival or mycotic clearance was found in 46 out of 50, 92% of the patients

  24. Conclusion solid organ transplantation 10 years experience of Ambisome treatment in solid organ transplant recipients at one single center has revealed: • AmBisome treatment was safe • AmBisome treatment was efficacious as seen as survival or mycotic clearance in 92% of proven fungal infections in SOT patients • Efficacy in suspected FI was 89 % clinical cures

  25. General conclusion; prophylaxis & treatment in transplantation • Prophylaxis with AmBisome • Efficacious in Liver transplantation • Treatment with AmBisome • Efficacious and safe in solid organ transplantation

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