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

THANK YOU! For queries, do contact me:

low.chian.yong@sgh.com.sg