1400-1430 (24-11) - jordi carratalá_joca ifi tos sao paulo 2012
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INVASIVE FUNGAL INFECTIONS
IN SOLID ORGAN TRANSPLANTATION
Jordi CarratalàDepartment of Infectious Diseases
Bellvitge Hospital-IDIBELL
University of Barcelona BellvitgeHospital
Invasive Fungal Infections in TransplantRecipients in Spain (1-09-03 / 01-03-05)
KIDNEY1330
LIVER979
HEART283
LUNG167
PANCREAS53
BMT944
TOTAL
Candida spp 41 (3%) 30 (3.1%) 11 (3.8%) 6 (3.6%) 2 (3.7%) 34 (3.6%) 124
Aspergillus spp 2 (0.2%) 5 (0.5%) 3 (1%) 10 (6%) 2 (3.7%) 56 (6%) 78
RESITRA
C. albicans 37%, C. glabrata 34%, C. krusei 13%, C. parapsilosis 11%, C. tropicalis 5%
Pappas PG. CID 2010
16.459 SOT recipients (Mar. 2001-Sep. 2005)
One-year cummulative incidence: 3.1%
Small bowel 11.6%
Lung 8.6%
Liver 4.7%
Heart 4.0%
Pancreas 3.4%
Kidney 1.3%
Pappas PG. CID 20101208 proven (42%) and probable (58%) IFI among
1063 SOT recipients
Pappas PG. CID 2010
575
343
312
184
103
467
Median time to onset of IFI
Pappas PG. CID 2010
TRANSNET. One-Year Mortality
Candidiasis 34%
Aspergillosis 41%
Non-Aspergillus molds 39%
Cryptococcosis 27%
Neofytos D. Transpl Infect Dis 2010
PATH (Prospective Antifungal Therapy Alliance)
Prospective observational study. USA/Canada (2004-2007)414 adult SOT recipients with 515 IFI episodes
Neofytos D. Transpl Infect Dis 2010
PATH (Prospective Antifungal Therapy Alliance)
3-month mortality 38% - Aspergillosis 52% - Candidiasis 24%
Risk Factors for Invasive Candidiasis
in Liver Transplant Recipients
Patient functional status
Age >65 yrs
High APACHE II score
Posttranspantation dialysis
Hyperglycemia and insulin therapy
Surgery
High requirements for transfusion
Retrasplantation
Choledochojejunostomy
Microbiology
Bacterial infection
Quinolone prophylaxis
Prolonged broad-spectrum ATB use
Immunodepression
Allograft rejection and
Corticosteroid therapy
CMV
Albano L. CID 2009
Contamination of graft or preservation fluid
18,617 kidney grafts
18 cases (12 donors) of graft-site candidiasis
Incidence, 1 case per 1000 grafts
13 Candida albicans
14 cases of renal arteritis (13 aneurysm)
2 graft site abscesses, 1 urinoma, 1 SSI
3 deaths, 9 nephrectomy
Pappas PG. CID 2010
n= 1208 n= 729
Lockhart SR. J Clin Microbiol 2011
Invasive Aspergillosis in SOT Recipients
Gavaldà J. CID 2005
Incidence: 1.4% (156/11014)
Mortality: 76.3% (119/156)
0
0,5
1
1,5
2
2,5
3
Lung Heart Liver Pancreas/Kidney Kidney
3%
2.4%
0.9% 0.9%
0.2%
80/3981
17/566
47/1920
2/230
10/4317
Risk Factor for Invasive Aspergillosis in SOT Recipients:
A Case-Control Study
Gavaldà J. CID 2005
Invasive Aspergillosis (n= 156)
Early-onset (3 months) 57%
Use of vascular amines >24h
Additional ICU stay
Posttransplantation renal failure
Posttransplantation dialysis
>1 episode of bacterial infection
CMV disease
Late-onset (>3 months) 43%
SOT at age >50 years
Posttransplantation renal failure
Chronic agraft rejection
Overimmunosuppressed state
>1 episode of bacterial infection
POPULATION SENSITIVITY (%) SPECIFICITY (%)
Hematologic malignancy 70 92
BMT 82 86
Pediatric BMT + malignancy 89 85
Solid organ transplant 22 84
Pfeiffer CD. Clin Infect Dis 2006
Clancy CJ. J Clin Microbiol 2007
Pasqualotto AC. Transplantation 2010
Singh N. Transplantation 2006
Survival at 90 days
Vorico + Caspo 68% (27/40)
Control group 51% (24/47) (P= .117)
Combination Therapy
Improved 90-day survival
Renal failure HR 0.32 (P= .022)
A. fumigatus HR 0.37 (P= .019)
2003-2005
1999-2002
The role of combination therapy in the treatment
of invasive aspergillosis as primary or salvage
therapy is uncertain and warrants a prospective,
controlled trial
Clin Infect Dis 2008
IDSA GUIDELINES
Primary Endpoint
277 SCT pts withproven/probable IA
Courtesy of KA Marr
Cryptococcosis in Solid Organ Transplant Recipients
Third IFI in frequency
Incidence ≈ 2.8% (0.3 – 5%)
- Alemtuzumab > risk
- Calcineurin inh. < disseminated
Late IFI (16 – 21 months)
Clinical Presentation
- 53 – 72% CNS or disseminated
- 54% lung, 8% bone or SST
- fungemia 30 – 40%
Cryptococcal Collaborative Transplant Study Group
Sun HY. CID 2010
Singh N. Transplantation 2005
83 recipients followed for a median of 2.1 and up to 5.2 years
Induction: L-AmB + 5FC (14 d) or L-AmB (4 w)
Consolidation: Fluconazole 400 – 800 mg/d (8 w)
Maintenance: Fluconazole 200 – 400 mg/d (6 -12 m)
Relapse: 1.3% (1/79 pts)
Less severe forms (lung): Fluconazole 400 mg/d (6 -12 m)
Calcineurin and mTOR Inhibitors as Antifungal Agents
Singh N. Transplantation 2004
Shoham S. Future Medicine 2012
Immune Reconstitution Syndrome (IRS) and Cryptococcosis
IRS occurs in 5-10% of pts (4-6 w after antifungal therapy).
Manifestations: aseptic meningitis, cerebral mass lesions,
arachnoiditis, hydrocephalus, lymphadenitis, lung nodules.
Cultures are usually negative.
IRS may be associated with higher rates of allograft loss.
Reduction as opposed to abrupt cessation of calcineurin
inhibitors, with tapering of corticosteroids.
The optimal treatment of IRS is unclear. Corticosteroids
may be considered in life-threatening situations.
Park BJ. Emerg Infect Dis 20111-year mortality: 39%
Zygomycosis in SOT Recipients
Cases typically develop within 3-6 months of Tx
Pulmonary disease predominates
Risk Factors:
- Receipt of corticosteroids
- Neutropenia
- Diabetes mellitus
- Renal failure at baseline
- Prior voriconazole and/or caspofungin use
- Liver transplantation
Singh N. J Infect Dis 2009
Overall the treatment success rate was 60%.
Renal failure (OR, 11.3; P= .023) and disseminated
disease (OR, 14.6; P= .027) were independently
predictive of treatment failure.
Surgical resection was associated with treatment
success (OR, 33.3; P= .003).
The success rate with liposomal AmB was 4-fold
higher, even when controlling for other variables.
San Juan R. Transplantation 2011
Fortún J. Transplantation 2009
Guidelines for the Treatment of IFI issued by the SEIMC
(2011 Update)
Fortún J. Enferm Infecc Microbiol Clin 2011
Thank you for your attention!
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