Systemic Fungal Infection

Systemic Fungal Infection
Dr. H. Harun Hudari, SpPD, FINASIM
DIVISION OF TROPICAL INFECTIOUS DISEASES

DEPARTMENT OF INTERNAL MEDICINE
MOH. HOESIN HOSPITAL
PALEMBANG
• The incidence of fungi infection has increased dramatically over 20 year-period
by 207%
• Candida species are the most common cause of infection in patients icu,
accounting for 85% of all documented mycosis :
o C. albicans is responsible for approximately 45- 58%
o C. non albicans ( C. krusei and C. glabrata ) has emerged and
increase to about 44%
• Fungi are the fourth leading pathogen in nosocomial infections in the USA
THE PROBLEM
o The mortality associated with systemic fungal infection

remains high (20 – 60%)
o The diagnosis is difficult :

 the clinical picture of systemic invasive disease is not
specific
 PCR, Mannan test promising but investigational
 blood culture has a low sensitivity
 its often hard to differentiate colonization from infection
in critically ill patients, especially when receiving broad
spectrum anti-bacterial
“ Clinical suspicion of paramount importance “
Bacterial Infection vs Fungal Infections
Gram +ve Gram -ve Fungal
Identical clinical syndrome in

severe infection/septic shock
Mortality
Bacterial severe sepsis/septic shock 30-50%
Fungal severe sepsis/septic shock 60%+
Dobbs.Bali Meeting 2004
Voriconazole vs Amphotericin-Fluconazole
Voriconazole Amphotericin P value
(N+248) B/Flu (N=122)
Primary 101 (41%) 50 (41%) 0.96

success
Secondary 162 (65%) 65% (53%) 0.23

success
2 weeks 130 (52%) 52 (42%) 0.99

After therapy
All cause 14 88 (36%) 52 (42%) 0.23

Wk mortality
Kulberg BJ et.al. Lancet 2005:366 1435 - 1442

Diagnostic studies
Fungus GM BG PCR
Aspergilus + + +
Fumingatus
Aspergilus + + +
non Fumingatus
Fusarium - + +
Zygomycetes - - +
Cryptococcus + + +
Candida + + +
Note: GM, galactomanan; BG, beta 1,3 glucan; PCR, polymerase chain reaction
Pamela Lipsett, SCCM,Honolulu,2008
The Question : why critically ill patients always at risk!!
As Clinician : to identified “the risk patient” as soon as possible

Diagnosis
Patients were classified according to the following
criteria:
i) Proven :
(a) positive blood culture
or (b) positive culture or histology from a normally
sterile body site or tissue obtained using a sterile
procedure;
• (ii) Probable :
fungal colonization and (a) Candida found in the
urine and/or in BAL (if direct microscopy revealed
yeast) and/or (b) response to antifungal treatment;
• (iii) Possible :
colonization without fulfilling the criteria above;
• (iv) Unlikely:
no fungal colonization.
Candida score
Identifying Patients : Prediction Rules
 Clinical sepsis = 2 points;

 Surgery = 1 point;
 TPN = 1 point;
 Multi-focal colonization = 1 point;
5 points possible
 If > 2.5 then sensitivity of 81% and specificity of 74%
 IF > 2.5 RR of infection 7.75*
 [95% CI 4.74, 12.66]
* Intend to treat as initial Empiric antifungal
Leon et al. CCM 2006.34

Antifungal Therapy
How to use Antifungal agent :
- Definition
SYSTEMIC ANTIFUNGALS
Ampho B Deoxycholate
Liposomal Ampho B (Ambisome)
Polyenes Ampho B Colloidal Dispersion
(ABCD)
Ampho B Lipid Complex (ABLC)
Itraconazole, Fluconazole,
Azole Voriconazole, Posatonazole,
Ravuconazole
Echinocandin Caspofungin, Anidulafungin

s Micafungin
Antimetabolit Flucytosine
e
Targets of antifungal therapy.
How Does One Choose ??
 Know the available agents
 Identify the likely fungal pathogen
 Be familiar with your local pathogens and the sensitivity of your

pathogens
 What is your patient looks like? Do you use azoles?
 Has the patient been exposed to azoles?

Why Do I Need to Know the Species?
Some species routinely either resistant or partially susceptible to azoles
Species FLU ITRA VORI CANDIN FLYCT AMPHO
C glabrata SDD - R SDD - R S S S S-I
C krusei R SDD - R S S I-R S-I
C lusitaniae S S S S S S-R
C. albicans S S S S S S
C.parapsilo S S S S S S-R
sis
S, susceptible; I, intermediate; R, resistance; SDD, susceptible dose-dependent
Pappas et al CID 2009: 48

Why Do I need to Know the Species ?
Molds FLU ITRA VORI CANDIN FLYCT AMPHO

Aspergillus
species
A. flavus R S S S I-R SDD-R
A. fumigatus R S S S I-R S
A. terreus R S S S I-R SDD-R
Pappas et al. CID 2004(38) Guidelines for Treatment of Candidiasis

“ Suspected Invasive Candidiasis or Candidemia “
Pappas et al. Treatment Guidelines for Candidiasis.CID 2009,March
-Hemodynamically unstable
-Septic / Neutropenia
-Recent Azole exposure
NO YES
Including : Including No infection

- No risk of infection C.glabrata ** of C.parapsilosis ##
- No risk of concomitant Endocardial
and CNS Candidiasis #
Fluconazole Echinocandin
400 -800 mg/ day iv Micafungin: 100 mg/day iv
Note : ** Risk of C.glabrata infection: elderly, cancer and diabetes patients ; # Echinocandin
(endondocardial candidiasis), Amphotericin B (endocardial and CNS candidiasis) ; ## C.parapsilo
sis (Amphotericin B or Fluconazole susceptible)
Echinocandins
• Caspofungin (Cancidas)
• Andulofungin (Eraxis)
• Micafungin (Mycamine)
Fluconazole remains one of the treatment of Candida infections
BUT,
Innate (C.krusei) or emerging (especially C. glabrata and C. guilliermondi)

resistance to azoles among non-albicans Candida spp. has been noted
in various regions in the world
SO,
Limit the use of Fluconazole as empirical therapy for candidemia in

critically ill patients
Pfaller et al. J Clin Microbiol, 2007,45

Bassetti et al. BMC Infect Dis, 2006,6
Take Home Message
• The incidence of systemic Candida infection in critically ill patients has
been increasing over the last two decades
• Critically ill patients cumulate risk factors for systemic invasive Candiasis
thats why : early identified of high risk of invasive candiasis is essential
• A biological tools are currently unavailable at the bedside, empirical treat

ment relies on clinical strategies on a “ High Risk Group Patients “
• Recently, Echinocandins (micafungin/ mycamin) has become suggested use

for prophylaxis, initial empiric and definitive antifungal therapy in modera
tely severe to severely illness or septic/netropenia and in unit with a high in
cidence of C.glabrata, C.krusei and Aspergillosis

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Systemic Fungal Infection

Dr. H. Harun Hudari, SpPD, FINASIM

DIVISION OF TROPICAL INFECTIOUS DISEASES

o The mortality associated with systemic fungal infection

o The diagnosis is difficult :

Gram +ve Gram -ve Fungal

Identical clinical syndrome in

Primary 101 (41%) 50 (41%) 0.96

Secondary 162 (65%) 65% (53%) 0.23

2 weeks 130 (52%) 52 (42%) 0.99

All cause 14 88 (36%) 52 (42%) 0.23

Kulberg BJ et.al. Lancet 2005:366 1435 - 1442

As Clinician : to identified “the risk patient” as soon as possible

 Clinical sepsis = 2 points;

Leon et al. CCM 2006.34

Echinocandin Caspofungin, Anidulafungin

 Know the available agents

 Identify the likely fungal pathogen

 Be familiar with your local pathogens and the sensitivity of your

 What is your patient looks like? Do you use azoles?

 Has the patient been exposed to azoles?

Species FLU ITRA VORI CANDIN FLYCT AMPHO

C glabrata SDD - R SDD - R S S S S-I

C krusei R SDD - R S S I-R S-I

S, susceptible; I, intermediate; R, resistance; SDD, susceptible dose-dependent

Pappas et al CID 2009: 48

Molds FLU ITRA VORI CANDIN FLYCT AMPHO

A. terreus R S S S I-R SDD-R

Pappas et al. CID 2004(38) Guidelines for Treatment of Candidiasis

Including : Including No infection

Innate (C.krusei) or emerging (especially C. glabrata and C. guilliermondi)

Limit the use of Fluconazole as empirical therapy for candidemia in

Pfaller et al. J Clin Microbiol, 2007,45

• A biological tools are currently unavailable at the bedside, empirical treat

• Recently, Echinocandins (micafungin/ mycamin) has become suggested use

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