Invasive Fungal Infection

In Sepsis

Dhani Redhono Harioputro

FK UNS Surakarta
 Introduction
• Sepsis is one of the most common causes of death,
fungal infections are often one of the complications
of sepsis Invasive Fungal Infections (IFI).

• IFI is a fungal infection that often occurs in deep

tissue infections, including candidiasis,
aspergillosis, histoplasmosis & cryptococcosis.

• The morbidity of sepsis cases with candida infection

ranges from 47 - 60% while Aspergillus is 30%.
• This often occurs in patients with conditions :
low immune levels, intravenous catheter
placement, mucositis due to chemotherapy,
the use of broad-spectrum antibiotics & the
use of cotricosteroids in therapy especially in
leukemia patients.

• In neutropenic patients with leukemia or bone

marrow transplantation, the frequency of
invasive candidiasis is 8 - 10%.
 Introduction
Invasive fungal infections (IFI) → significantly ↑
at risk immunocompromised population
↓
• Cancer
• Hematological malignancies
• Allogeneic bone marrow/hematopoietic
stemcell transplant recipients
• HIV
Early diagnosis is usually difficult to establish
→ Mostly life threatening
 Introduction
Aspergillus and Candida species are involved.
Distributed in soil, plant debris & other organic
substrates
→ Infection can be transmitted by :
Inhalation of spores
Percutaneous inoculation in cutaneous
Subcutaneous infections
Penetration into the mucosa
Ingestion of contaminated food or drink
 Underlying disease in invasive
Aspergillosis
595 patients

None
Other BMT/Auto
6% 2% 7%
Pulm BMT/Auto
9%
BMT/Allo
Other Immune BMT/Allo Hematologic
6% 25% Solid Transplant
AIDS
AIDS [PERCENTAGE]
Other Immune
Pulm
Solid Transplant Other
9%
None
Hematologic
28%

Patterson et al, Medicine

 A comprehensive approach to
diagnose IFI

Host

Laboratory Diagnosis Clinical

Imaging
Aspergillosis syndrome
• Cough (92%)
• Thoracic pain (76%)
• Hemoptysis (54%)
• Fever
Clinical aspects
• Neurological signs
• Nasal bleeding
• Nasal discharge
• Skin lesions
Invasive Pulmonary Aspergillosis

Clinical aspects
 Dilemmas in diagnosing IFI
Clinical symptoms are not spesific
Fungi can be both colonizers and pathogens, and
even laboratory contamination
 Objective evidence usually occurs late in the
course of infection
Various laboratory methods, like the Aspergillus
GM immunoassay, 1,3-ß-D-glucan (BG) assay or
polymerase chain reaction (PCR) have been
developed for better diagnosis.
Defining Diagnosis IFI

Host
factor

Clinical
feature

Mycology
 Defining
Defining infection - Host factors Host Factor

Neutropenia
Neutropenia<<500
500 >>33weeks
weekscorticosteroids
corticosteroids

Host >>44days
daysunexplained
unexplained
fever
fever despitebroad
despite broad
<36°C factor
<36°Cor
or>>38°C
38°Cand
and spectrum antibiotics
spectrum antibiotics
• • prior mycosis
prior mycosis
• • AIDS
AIDS
• • Immunosuppressives
Immunosuppressives
• • > 10 days neutropenia Graft
> 10 days neutropenia Graftversus
versusHost
HostDisease
Disease

Invasive Mycoses
Ascioglu et al 2002 Fungal
Infections
Mycoses
Study
Cooperative Study
Clin Infect Dis 34:7-14 Group Group
Group
 Defining Clinical Feature

Lower
Lower respiratory
respiratory tract
tract infection
infection Chronic
Chronic disseminated
disseminated candidiasis
candidiasis
Halo sign Bull’s eye lesions in liver or spleen
Air-crescent sign
MAJOR
cavity

Sinonasal
Sinonasal infection
infection Clinical
Radiological evidence feature

CNS
CNS infection
infection Disseminated
Disseminated fungal
fungal infection
infection
Radiological evidence Unexplained papular or nodular skin lesions
Chorioretinitis
endophthalmitis
 Defining Clinical Feature

Lower
Lower respiratory
respiratory tract
tract infection
infection CNS
CNS infection
infection
Cough, chest pain, haemoptysis, dyspnoea CSF No pathogens
Physical finding of pleural rub no malignant cells
Any new infiltrate not fulfilling major criterion abnormal biochemistry
abnormal cell count
Focal neurological
seizures
MINOR Clinical hemiparesis
cranial nerve palsy
Feature Mental changes
Meningeal irritation
Sinonasal
Sinonasal infection
infection
Nasal discharge, stuffiness
Nose ulceration, eschar or epistaxis
Periorbital swelling
Maxillary tenderness
Black necrotic lesions or perforation of the hard-palate
 Defining Mycology

Culture of mould from tissue, aspirate BAL or sputum

mould seen in sinus aspirate Mycology

Fungi seen in tissue or sterile body fluids antigen in BAL, CSF or blood
 Proven IFI

Host Clinical
factor + features + Tissue
+ Mycology
 Probable IFI

Host Clinical
factor + features + Mycology
 Posibble IFI

Clinical
features

Host
factor + OR

Mycology
 EORTC/MSG Definitions of Aspergillosis

Clinical
Host factor features Mycology

GVHD
+ + antigenaemia

Halo sign on chest CT scan

OR
cough

+
pleural rub
 EORTC/MSG Definitions of Candidosis

Clinical
Host factor features Mycology

+
Neutropenia

Small, peripheral, target-like

abscesses (Bull’s eye) in liver and/or
spleen demonstrated by CT, MRI or
ultra sonogram.

+/-
elevated alkaline phosphatase
 NON INVASIVE DIAGNOSTIC
TESTS FOR FUNGAL INFECTIONS
EORTC
IFICG

Species specific PCR

PCR

Genus specific galactomannan

mannan
capsular antigen

Panfungal-PCR
Fungi
(13)-ß-D-glucan

Fungi and CRP, PCT,

bacteria interleukin-6 (IL-6)
 Antigen detection in the
diagnosis of IFIs

(13)--D-glucan of most fungi

Except : Zygomycetes, Cryptococcus,
Sensitivity 90%; specificity 100%
Galactomannan of Aspergillus, Penicillium :
sandwich enzyme-linked immunosorbent assay,

detection limit 0.5 to 1.0 ng/ml

Mannan of Candida : sandwich enzyme-linked
immunosorbent assay
 (13)-ß-D-glucan (BDG)

It’s a component of the fungal cell wall.

Sensitivity 90%; specificity 100%
FDA approved 2004 as a support for the diagnosis of IFI
PANFUNGAL TEST

Positive in Not detect

Aspergillus Cryptococcus
Candida Zygomicetes
Pneumocystis carinii
Fusarium
Trichosporon
Saccharomyces cerevisiae
Acremonium
Histoplasma capsulatum
Considerations for selecting the most
appropriate drug
 Conclusion
Diagnosis of IFI → dilemmas
Diagnostic criteria should consider :
Host factors
Clinical features,
Imaging &
Mycology findings
HIV/AIDS is one of the most host risk factors for IFI
Early detection diagnostic approaches are the antigen-
detection tests and or PCR.
“
Thank You