ANTIFUNGAL AGENTS FOR

PREVENTING FUNGAL INFECTIONS

IN CRITICALLY ILL PATIENTS

BAS 2021
OUT LINE
• BACKGROUND
• RISK FACTOR
• FUNGAL INFECTION
• ANTI FUNGAL
• CONCLUSION
 kat Angka kematian pada sepsis berat dan syok

ing
sepsis berkisar 61%.
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Rivers
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Bone
Angka kejadian sepsis dapat mencapai
1992 750.000 kasus per tahun

Surviving Sepsis Campaign

Septic shock remains a major source of morbidity and mortality
in critically ill patients (SSC) 2018
R. P. Dellinger, et al. Intensive Care Medicine.Surviving Sepsis Campaign: International Guidelines for
Management of Severe Sepsis and Septic Shock, 2012. February 2013, Volume 39, Issue 2, pp 165–
228. ISSN: 0342-4642 (Print) 1432-1238 (Online)
 Endotoxin and other PATOFISIOLOGI
microbial product
Complement SEPSIS
activation

Factor XII

Direct and
TNF, IL-1, HMGB1
indirect
Endothelial activation Cytokines and
cytokine-like mediators

Procoagulant Anti-fibrinolytic
IL-6, IL-8, NO, PAF, reactive IL-10, apoptosis, sTNFR
TF oxygen species, etc
TFP1, thrombomodulin, protein C Secondary anti-inflamatory
mediators
MICROVASCULAR SYSTEMIC

THROMBOSIS (DIC) VASODILATATION EFFECTS IMMUNOSUPRESSION

INCREASED PERMEABILITY
  DECREASED PERFUSION
TISSUE ISCHEMIA
 
Fever, diminished
myocardial contractility,
metabolic abnormalities

Adrenal Insufficiency MULTIORGAN FAILURE

 3

Sepsis cause of candida increasing 207%, from 5231 cases in 1979 to 16.042 cases in 2000,
The morbidity and mortality caused by invasive fungal infections
amongst hospitalized patients has increased over recent decades

(Beck-Sague 1993; Jarvis 1995)

Immunocompromised , neutropenia , organ transplant recipients,

recent abdominal surgery, dialysis, central venous catheterization,
parenteral nutrition, broad-spectrum antibiotic therapy
(Blumberg 2001, Borzotta 1999, Fridkin1996, McKinnon 2001, Pittet 1994).

Candidaemia has been reported to be associated with prolonged

length of ICU stay , excess economic costs . Recognized and treated
late, available diagnostic tests.
(Leleu 2002, Pelz 2000, Kanda 2000, Rentz 1998).
There is no consensus regarding the use of antifungal
prophylaxis in critically ill patients

(Calandra 2002; Ostrosky 2003; Rex 2001; Sobel 2001).

EPIC II (2007) consist of 1265 ICU di 75 country  19%

patogen in ICU is Candida (17%) and Aspergillus.

Morrell et  delay >12 hour in initiating empiric antifungal

therapy with an increase in mortality due to candidemia of
200%
 Morrell et al identified the
delay of >12 hour in initiating empiric antifungal
therapy with an increase in mortality due to
candidemia
of 3 kali lipat
Candida BSI are
deadly - crude
mortality » 25-60

– More than
half were
due to non-
albicans sp.
DON’T FORGET TO
USE ANTIFUNGAL
Diagnostic Strategies

CLINICAL
DATA

Invasive candidiasis

RISK FACTOR LABORATORY

 inhibit synthesis
β-(1–3)-D-glucan

Creating pores that allow

Inhibit leakage of cell
ergosterol
fungal cell
membrane
Journal of Critical Care (2013) 28, 717–727
 A Cochrane database
Antifungal prophylaxis
patients can reduce
mortality by 25%
PROPHYLAXIS IN ICU
CANDIDEMIA IN
NONNEUTROPE
NIC
PROPHYLAXIS TRANSPLANT RECIPIENTS,
ICU PATIENTS, CHEMOTHERAPY, AND STEM
CELL TRANSPLANT RISK OF CANDIDIASIS in
NEUTROPENIC PATIENTS
Aspergillosis
 CONCLUSION
• Invasive candidiasis is a feared infection with mortality similar to that
of septic shock (40–60%).
• Candida and aspergilosis casue of fungal infecton
• Invasive fungal infections are important causes of morbidity and
mortality among critically ill patients.
• Early antifungal therapy is pivotal for mortality reduction.
• Use empirical antifungal therapy ( Scoring, Risk factor, Clinical )