emerging fungal infections in ......cy low, c rotstein. emerging fungal infections in...
TRANSCRIPT
EMERGING FUNGAL INFECTIONS IN
IMMUNOCOMPROMISED PATIENTS
DR LOW CHIAN YONG MBBS, MRCP(UK), MMed(Int Med), FAMS Consultant, Dept of Infectious Diseases, SGH
Introduction
The incidence of invasive fungal infection (IFI) is rising
From 1980 through 1997, the annual mortality due to IFI in the
US increased from 1,557 to 6,534 (320% increase over 17
years)
Increasing pool of immunocompromised patients e.g. over
23,000 organs were transplanted in US in 2008 (2x that 10
years ago)
Also, newer and more potent chemotherapeutic agents and
regimens
Not least antibiotic pressures from newer antifungal agents
The evolving epidemiology
Increasing incidence of mold infections esp.
aspergillosis in the hematopoietic stem cell
transplant (HSCT) recipients and neutropenic
patients with acute leukemia.
The increasing incidence of non-albicans Candida spp..
The emergence of zygomycosis.
G Chamilos et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica 2006; 91:986-989
Spectrum of invasive mold infection over time
DP Kontoyiannis et al. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50:1091–1100
6-month and 12-month cumulative incidence (CI) for invasive fungal infection (IFI) in the HSCT cohort.
PG Pappas et al. Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010; 50:1101–1111
6-month and 12-month cumulative incidence (CI) for invasive fungal infection (IFI) in the SOT cohort.
The evolving epidemiology
Increasing incidence of mold infections esp. aspergillosis in the
hematopoietic stem cell transplant (HSCT) recipients and
neutropenic patients with acute leukemia.
The increasing incidence of non-albicans Candida
spp..
The emergence of zygomycosis.
MA Pfaller et al. Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin Microbiol Rev 2007;20(1):133–163
Species distribution of Candida from cases of invasive candidiasis
MA Pfaller et al. Candida Bloodstream Infections: Comparison of Species Distributions and Antifungal Resistance Patterns in Community-Onset and Nosocomial Isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob Agents Chemother 2011; 55(2): 561–566
Frequency of antifungal resistance among community-onset and nosocomial bloodstream infection isolates of Candida spp.: SENTRY Antimicrobial Surveillance Program (2008-2009)
MA Pfaller et al. Candida Bloodstream Infections: Comparison of Species Distributions and Antifungal Resistance Patterns in Community-Onset and Nosocomial Isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob Agents Chemother 2011; 55(2): 561–566
Frequency of antifungal resistance among community-onset and nosocomial bloodstream infection isolates of Candida spp.: SENTRY Antimicrobial Surveillance Program (2008-2009)
The evolving epidemiology
Increasing incidence of mold infections esp. aspergillosis in the
hematopoietic stem cell transplant (HSCT) recipients and
neutropenic patients with acute leukemia.
The increasing incidence of non-albicans Candida spp..
The emergence of zygomycosis.
Increasing use of voriconazole as prophylaxis, empirical, preemptive, and targeted treatment for invasive aspergillosis in patients with hematologic malignancy.
Associated rise in incidence of zygomycosis.
As shown in case series in immunocompromised patients1, case-control study in leukemic and HSCT recipients (10x risk)2, case-control study in SOT recipients (4.4x risk)3.
1Int J Infect Dis 2010, 14(Suppl 3):e100-3
2J Infect Dis 2005, 191:1350-60
3J Infect Dis 2009, 200:1002-11
The risk groups and risk factors for invasive fungal infection
Patients with acute leukemia
Hematopoietic Stem Cell Transplant recipients
Solid Organ Transplant recipients
Patients with acute leukemia
Status of leukemia
De novo, post-remission, relapsed, refractory
Type of leukemia
ALL vs AML vs CML vs hairy cell etc
Depth and duration of leucopenia
Types of chemotherapeutic agents
Breaches in the skin
CVC line
Breaches in the bowel
Mucotoxic chemotherapeutic agents
Hematopoietic stem cell transplant recipients
Dynamic interactions: Host, graft, complications of procedures
Host
Older age
Transplant factors
HLA mismatch
Use of immunosuppressives during pre-engraftment
Post-engraftment complications
GVHD
DP Kontoyiannis et al. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50:1091–1100
Invasive fungal infection among hematopoietic stem cell transplant (HSCT) recipients in the TRANSNET surveillance cohort, stratified by type of HSCT
Solid-organ transplant recipients
Types of organ transplant
Small bowel (1-yr cumulative incidence for IFI is 11.6%)
Kidney (1.3%)
Rejection and immunosuppressives
High dose steroids
ATG use
Medical and surgical factors
DM and prolonged dialysis pre-transplant (renal)
Fulminant liver failure, retransplantation, dialysis (liver)
Older donor age, enteric drainage, PAK transplant (pancreas)
Prolonged ischemia time (lung)
PG Pappas et al. Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010; 50:1101–1111
Cumulative incidence curve of first invasive fungal infection (IFI) according to SOT type
CY Low, C Rotstein. Emerging fungal infections in immunocompromised patients. F1000 Med Rep 2011, 3:14
Timing of invasive fungal infections after organ transplantation
Diagnostics
Traditional culture-based techniques
Histopathology
Galactomannan Ag or PCR (serum and BAL)
β–D–glucan
CT scans
Management
High index of suspicion
Prompt diagnosis
Early initiation of antifungals
monotherapy or combination
Reduction of immunosuppressive therapy (where possible)
Reversal of neutropenia
GCSF or Donor Lymphocyte Infusion
Surgery
Management CY Low, C Rotstein. F1000 Med Rep 2011, 3:14
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