INVASIVE ASPERGILLOSIS - PowerPoint PPT Presentation

Loading...

PPT – INVASIVE ASPERGILLOSIS PowerPoint presentation | free to download - id: bed3f-ZDc1Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

INVASIVE ASPERGILLOSIS

Description:

Neonatal survivorship Congenital IDS. Antimicrobials Fungal promotion ... radiograph CT. Normal Non-specific Normal Halo signs /- changes other changes. 6 15 0 21 ... – PowerPoint PPT presentation

Number of Views:55
Avg rating:3.0/5.0
Slides: 45
Provided by: Mik7345
Learn more at: http://www.fungalforum.com
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: INVASIVE ASPERGILLOSIS


1
INVASIVE ASPERGILLOSIS
  • Management with liposomal amphotericin B

Michael Ellis
2
IPA/IFI THE INTRINSIC SETTING
  • Leukemia
  • Cancer
  • Multiple myeloma
  • Malnutrition

3
IPA/IFI THE EXTRINSIC SETTING
  • Socio-behavioural HIV
  • Longevity Super old
  • Extreme prematurity
  • Neonatal survivorship Congenital IDS
  • Antimicrobials Fungal promotion
  • Intravenous device Mechanical disruption
  • Orifice cannulation Mucosal
    disintegrity
  • Surgery Repetitive/extensive

4
Neutropenia risk
50 0
Duration of neutropenia
Risk infection/1000 days
Neutrophils lt100 100-500 500-1000
1000-1500 gt1500
5
autopsies in pts with cancer positive for IFI
80
Data from 8 studies
All IFI
40
ASPERGILLUS
1950
1970
1990
6
FEBRILE NEUTROPENIA AND IFI
  • 92 patients with febrile neutropenia
  • panfungal PCR q weekly
  • 34 PCR ve
  • Hebart et al Br J Haematol 2000

7
IPA in prolonged neutropenia
  • 362 high-risk treatment episodes
  • Laminar air flow
  • HEPA
  • Itraconazole/CAB
  • ve galactomannan 12.1 all neutropenic episodes

Maertens et al Blood 2001
8
IA IN STEM CELL RECIPIENTS
  • cumulative
  • incidence 12
  • 4
  • 1990 1998

Marr et al Abstract 2001 ASH 2001
9
IA in Hematological PatientsOutcome
  • 222 studies
  • gt 1995
  • 50 studies

Case fatality rate
Lin et al CID 2001
10
Management of IA
AMBISOME
10 drug
Immune-modulation
surgery
20 drug
11
CAB toxicity costs
  • 707 admissions/4 years to Brigham and Womens
  • 50 had malignancy
  • CAB for 33 documented IFI, 66 ARNF
  • Acute renal failure in 212/707

Baseline creatinine ? 50
Bates et al CID 2002
12
CAB toxicity costs
  • MORTALITY
  • ARF ARF-
  • 54 16 p 0.001
  • Balanced for sepsis/infection
  • BMTx and total dose CAB more in ARF group
  • Adjusted for age, base creatinine, illness
    severity
  • Re-analysed in last two admission days

Bates et al CID 2002
13
CAB toxicity costs
COST OF SURVIVING CAB associated ARF
Confounders eg indications for Rx and severity of
illness although corrected for may have still
existed
14
IPA
CAB 0.5mg
CAB 0.8mg
CAB DC
CAB 0.3mg
Day 1 4 7
10
2cms/day in vitro
15
Liposomal Amphotericin B
  • Infrequent toxic related dosing limitations
  • Less indication for steroids, opiates
  • Short infusion time
  • Dose escalation possible

16
Liposomal versus conventional amphotericin B
  • Animal data
  • Human open trial
  • Prospective clinical and other

17
Liposomal versus conventional amphotericin B
Intratracheal inoculation Neutropenic rabbits
lobes infected
Francis et al JID 1994
18
LIPOSOMAL VERSUS CONVENTIONAL AMPHOTERICIN B
SURVIVAL
100
Rx none CAB1 LAB1 LAB5 LAB10
Francis et al JID 1994
19
DISSEMINATION OF ASPERGILLUS
100
Liver and spleen
R lung
Rx none CAB1 LAB 1 LAB 10
Rx none CAB1 LAB 1 LAB 10
Leenders JAC 199638215
20
Concentration dependency
  • g/ml and log cfu/g

Groll et al JID 2000
21
Liposomal versus conventional amphotericin B
  • 13 studies involving 1091 patients
  • Invasive aspergillosis
  • LAB other forms
  • 76 patients 414 patients
  • Response 63 59-66 Response 47
    34-67

Wong-Beringer CID 1998
22
CAB v LAB
  • Invasive fungal infections 106
  • Enrolled/analysed for efficacy 66
  • Invasive pulmonary aspergillosis 40
  • CONVENTIONAL AB AMBISOME
  • 1 mg for 3 weeks 5 mg for 3 weeks
  • 0.7 mg 3mg

Leenders et al Br J Haematol 1998
23
CAB v LAB responses
24
AmBisome optimal dosing
  • Animal candida thigh infection model
  • Neutropenic animal models
  • Previous human observations
  • In depth case studies
  • Histopathologic

Maximum tolerated dose
25
LIPOSOMAL VERSUS CONVENTIONAL AMPHOTERICIN B
SURVIVAL
100
Rx none CAB1 LAB1 LAB5 LAB10
Francis et al JID 1994
26
Treatment failure in IPA and tissue drug levels
  • MIC AB Sensitivity Lung AB levels
  • ?g/ml ?g/gm
  • A.Fumigatus 0.125-0.5 S 0.22 Infected
  • A.flavus 1 S 0.67 Normal
  • A.flavus 2 LS 6.63 Liver

Paterson et al ICAAC 2000
27
HIGH DOSE CAB
11 PTS ARNF ON CAB 0.5 MG
4 PTS
IA
N 15
N 1
0.5 MG
1- 1.5 MG
N 14
0/1 SURVIVAL
13/14
Burgh J Clin Oncol 198751985
28
EORTC 19923 probable/proven IPA
29
EORTC 19923 SURVIVAL
100
1 MG
4 MG
Log rank p 0.58
0 1 2 3 4 5 6 months
30
Proven IPA
31
EORTC 19923 summary
  • AmBisome at 1 mg or 4 mg efficacious in treating
    IA in neutropenic patients, appears to be
    superior to conventional amphotericin B and less
    toxic. The results suggest that the 4 mg dose has
    advantages over a 1 mg dose.

32
Hepatic candidiasis
CANDIDA ANTIGEN
CANDIDA ANTIBODY

30
1.5
1.0
10
0.5
33
Hepatic candidiasis
LAB 5mg
CASPOFUNGIN
LAB 10mg
LIVER image
39 38 39 39 38
37
TEMP
400 110 150 190
100 30 15
CRP
1 21 25
42 56
70
DAY Rx
34
IPA early diagnosis-AmBisome treatment link
  • HALO SIGN
  • The radiologic counterpart of the
    histopathologic early IPA lesion

35
(No Transcript)
36
IPA early diagnosis-AmBisome treatment link
  • ARNF LAB 1-3 mg
  • 96hr HRCT for CT HALO or other
  • q7d
  • 2-4 gm
  • 5 mg
  • Worsens Stable
  • 8 10 mg 5, 4, 3 mg

NO
YES
37
IPA early diagnosis-AmBisome treatment link
  •  21 patients
  •  
  •   Plain chest
    Chest
  • radiograph
    CT
  •  
  •  
  • Normal Non-specific Normal Halo
    signs/-
  • changes other changes
  •  
  • 6 15 0
    21

38
DISTRIBUTION OF CT FINDINGS
39
ARNF TO 1ST VE SCAN
MEDIAN
40
IPA early diagnosis-AmBisome treatment link
  • 100
  • 50


LINKED
RESPONSE
LITERATURE
CRUDE MORTALITY
ATTRIB MORTALITY
0
41
IPA early diagnosis-AmBisome treatment link
  • 9 DEATHS
  • IPA 2pts non-IPA 7pts
  • Recurrence/progression 2/2 Bacterial sepsis
    3
  • Dosage 1.5, 3 mg Hematologic disease 3
  • Growth factors 1/2 Cerebral hemorrhage 1
  • High fungal burden 2/2

42
CT SERIES IPA FROM DAY 16 ARNF
PATIENT HAS AIR CRESCENT IN RUL, STARTS TREATMENT
WITH AMBISOME
DAY 16
DAY 30
DAY 120
43
Impact of early diagnosis and Rx on survival in
IPA
survival
100
since 1992
before 1992
50
0 60 120 180 days after diagnosis
Caillot et al J Clin Oncol 1992 15 139-147
44
IPA early diagnosis-AmBisome treatment link
  • CONCLUSION
  • An early diagnosis of IPA linked to early high
    dose AmBisome and supportive hematologic care
    offers a good treatment option
About PowerShow.com