EMERGING FUNGAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS

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1 EMERGING FUNGAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS DR LOW CHIAN YONG MBBS, MRCP(UK), MMed(Int Med), FAMS Consultant, Dept of Infectious Diseases, SGH

2 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

3 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.

4 Spectrum of invasive mold infection over time 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 ( ). Haematologica 2006; 91:

5 6-month and 12-month cumulative incidence (CI) for invasive fungal infection (IFI) in the HSCT cohort. DP Kontoyiannis et al. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, : Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50:

6 6-month and 12-month cumulative incidence (CI) for invasive fungal infection (IFI) in the SOT 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:

7 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.

8 Species distribution of Candida from cases of invasive candidiasis MA Pfaller et al. Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin Microbiol Rev 2007;20(1):

9 Frequency of antifungal resistance among community-onset and nosocomial bloodstream infection isolates of Candida spp.: SENTRY Antimicrobial Surveillance Program ( ) 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, Antimicrob Agents Chemother 2011; 55(2):

10 Frequency of antifungal resistance among community-onset and nosocomial bloodstream infection isolates of Candida spp.: SENTRY Antimicrobial Surveillance Program ( ) 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, Antimicrob Agents Chemother 2011; 55(2):

11 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.

12 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 patients 1, casecontrol study in leukemic and HSCT recipients (10x risk) 2, case-control study in SOT recipients (4.4x risk) 3. 1 Int J Infect Dis 2010, 14(Suppl 3):e J Infect Dis 2005, 191: J Infect Dis 2009, 200:

13 The risk groups and risk factors for invasive fungal infection Patients with acute leukemia Hematopoietic Stem Cell Transplant recipients Solid Organ Transplant recipients

14 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

15 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

16 Invasive fungal infection among hematopoietic stem cell transplant (HSCT) recipients in the TRANSNET surveillance cohort, stratified by type of HSCT DP Kontoyiannis et al. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, : Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50:

17 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)

18 Cumulative incidence curve of first invasive fungal infection (IFI) according to SOT type 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:

19 Timing of invasive fungal infections after organ transplantation CY Low, C Rotstein. Emerging fungal infections in immunocompromised patients. F1000 Med Rep 2011, 3:14

20 Diagnostics Traditional culture-based techniques Histopathology Galactomannan Ag or PCR (serum and BAL) β D glucan CT scans

21 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

22 Management CY Low, C Rotstein. F1000 Med Rep 2011, 3:14

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