Title: Ten years experience of liposomal amphotericin B, AmBisome treatment in solid organ transplant recipients (SOT)
1Ten years experience of liposomal amphotericin B,
AmBisome treatment in solid organ transplant
recipients(SOT)
2Our 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)
3Fungal 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
4Incidence of invasive fungal infections at our
center during the time periods 1989 to 1994 1996
- Organ n VFI 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
5AmBisome prophylaxis
- Liver transplant recipients
- Transplantation. 59 1 45-50, 1995.
- Transplant. Proc.27 1195-1198, 1995.
6Study 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
7Results Adverse Events LTX prophylaxis all 84
patients
8Results invasive fungal infections after
prophylaxis in LTX, first year
plt0.01
plt0.05
9LTX 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
10LTX 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
11LTX 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
12AmBisome treatment
- Solid organ transplant recipients,
- 10 year data
13SOT 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
14SOT 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
15AmBisome treatment data in SOT
- Fungal Infection
- AmBisome treatment Verified Suspected Prophylact
ic - Duration (days),
- mean SD (median) 2317(18) 1815 (14) 1619
(7) - range 4-81 1-80 1-83
- Max. dose (mg),
- mean SD (median) 2.01 (1.8) 1.70.9
(1.4) 1.40.8 (1.0 ) - range 0.7-5.5 0.7-5 0.6-6
- Total dose (g),
- mean SD (median) 1.71.7 (0.95) 1.41.3
(1.1) 0.60.5 (0.4) - range 0.05-8.1 0.06-8 0.03-2.4
16Days with AmBisome
17AmBisome dose (mg/kg/d)
18Total dose AmBisome (gram)
19Adverse 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
20Kidney function before, during and after AmBisome
treatment measured as S-creatinine
21Efficacy 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
22Proven 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)
23Efficacy, 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
24Conclusion 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
25General conclusion prophylaxis treatment in
transplantation
- Prophylaxis with AmBisome
- Efficacious in Liver transplantation
- Treatment with AmBisome
- Efficacious and safe in solid organ
transplantation