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Criterii
Neutropenie < 500 PN/mmc timp de > 10 zile
Febr persistent >96 ore refractar la terapie antibiotic
adecvat
Temperatur > 38C sau < 36C sau una din urmtoarele
condiii n utlimele 60 zile:
Neutropenie (> 10 zile)
Utilizare recent sau curent de imunosupresoare cu 30
zile nainte
Existena unui episod dovedit sau probabil de infecie
fungic invaziv ntr-un episod anterior de neutropenie (>
10 zile)
Coexistena SIDA
Semne i simptome sugestive pentru sindromul gref contra
gazd
Utilizare prelungit de corticoizi (> 30 zile) cu 60 zile
anterior internrii
Criterii microbiologice
minore
Candidoz diseminat
majore
Forme filamentoase
- Aspergilus
- Fusarium
- Scedosporium
- Mucor...
Forme dimorfe
- Histoplasma
- Coccidioides
- Blastomyces
Nr. izolate
Inciden (%)
3908
1928
1354
934
31.9
15.7
11.1
7.6
Inciden
%
32
16
11
8
6
5
5
4
1
1
Neutropenie
9%
4%
Mortalitate
%
21
25
32
40
24
27
28
33
26
23
C. albicans
54%
C. glabrata
16%
Adapted from Pfaller MA et al and The SENTRY Participant Group Antimicrob Agents Chemother 2000;44:747-751.
Aspergillus pn la
90%* la transplantai
11%
Candida glabrata
42%
21%
Candida tropicalis
Candida parapsilosis
26%
altele
others
53%
albicans
Neutropenici
Neoplasm
nutriie parenteral
Transplant
ageni anti-anaerobi
Gazd imunocompromis
Intervenie chirurgical
Cateterism intravascular
Blumberg HM, Jarvis WR, Soucie JM et al and the NEMIS Study Group Clin Infect Dis 2001;33:177-186;
Garber G Drugs 2001;61(suppl 1):1-12.
National Epidemiology of Mycosis Survey (NEMIS) was a prospective, multicenter study conducted at 6 US sites from 1993-1995 to examine rates of risk factors for
the development of candidal bloodstream infections (CBSIs) among patients in surgical and neonatal ICUs >48h. Among 4276 patients, 42 CBSIs occurred.
Leucemie ac.
Transplanturi
Arsuri
Chirurgie GI
Prematuritate
Copii
Factor de Risc
Antibiotice
catetere IV
Candida
colonizare
Hemodializ
ATI
1.7
7.2
10.4
10.4
?
Su
pr
av
ie
u
ir e
Risc Crescut
Candidiaz
Deces prin
candidemie
Deces prin
boal de
fond
EORTC
IFICG
Incidena
tropicalis
lusitaniae
glabrata
parapsilosis
krusei
guillermondii
Candida
albicans
ormans
Cryptococcus neof
Aspergillus species
Alternaria
Pseudallescheria boydii
Coccidioidomycosis
Mucor/Rhizopus
Rhodotorula
Penicillium marneffei
Fusarium
Trichosporon beigelii
Malassezia furfur
Blastomycosis
Timp
EORTC
IFICG
Creterea Aspergillus-ului
1-2 mm / or
G.P. Bodey*
15-30% din pacientii cu Candida
Invasiva autopsiai
Nu au primit
niciodat terapie
sistemic
????
antifungic
!!!!
DCI
Produs
Prezentare
An
Cp
1939
1951
Inhibitori ai
mitozei
Griseofulvin
Griseofulvin
Poliene
Amfotericina B
Fungizone
Amfo B
liposomal
Abelcet
IV
1995
Pyrimidine
Flucitozin
Ancotil
IV, Cp
1957
Azoli
Ketoconazol
Nizoral
Cp
1982
Fluconazol
Triflucan
IV, Ov.
1990
Itraconazol
Sporanax
Ov.
1992
Voriconazol
Vfend
IV, Ov.
2002
Alilamine
Terbinafina
Lamisil
Cp
1994
Candine
Caspofungin
Cancidas
IV
2001
Fungii
Membrana cell
- ergosterol
Perete cell.
- chitin
- manoproteine
- -glucan
Sinteza de acizi
nucleici
allylamines
(e.g., terbinafina)
5-flucytosine
sodarine
squalene
sinteza de chitin
Azolii (e.g.,
fluconazole)
lanosterol
factorul de elongaie
nikkomycin
K
Inihiia manoproteinelor
pradimicin
Polyene (e.g.,
amphotericin B)
ergosterol
Sinteza de
(1,3)-D-glucan
Candine (e.g.,
caspofungin)
MEMBRAN
5-FLUORO-CITOZIN
NUCLEU
SORDARIN
GRISEOFULVIN
Agentul
Locul de aciune
Activitate
Implicaii Clinice
Amphotericin-B Membran
Cupleaz ergosterolul;
produce moarte cell.
Azolii
Membran
Medicament
Fungizon
Avantaje
Activ mpotrivaCandida,
Aspergillus
Dezavantaje
Nefrotoxicitate
Potenial de toxicitate
Nefrotoxicitate
Potenial de toxicitate
Nefrotoxicitatea este mai mic Ratele de reacie acut determinate de
dect n cazul amfotericinei B infuzie nu difer substanial de cele
convenionale
observate n cazul amfotericinei B
convenionale
Azoli
Fluconazol
Itraconazol
Analog nucleozidic
Flucitosin
Toxicitate selectiv
Andriole VT J Antimicrob Chemother 1999;44:151162; Groll AH Adv Pharmacol 1998;44:343-500; Onishi J Antimicrob Agents Chemother 2000;44:368377; Stone
EA Clin Ther 2002;24(3):351-377; Sporanox (Itraconazole) Injection Prescribing Information; Fluconazole Prescribing Information
Noile antifungice
Triazoli
Voriconazol (Vfend)
Posaconazol
Ravuconazol
Echinocandine
Caspofungin (Cancidas)
Mycafungin
Anidulafungin
Nystatin liposomal (Nyotran)
Sordarin
Nyckomycine
Intermediar
Slab
[2,016,0 g/ ml]
[16,0>64,0 g/ ml]
Speciile de Candida
Histoplasma capsulatum
Cryptococcus neoformans
Speciile de Aspergillus
Coccidiodes imitis
Speciile de Fusarium
Saccharomyces cerevisiae
Speciile de Alternaria
Blastomyces dermatitidis
Speciile de Rhizopus
Speciile de Curvularia
Sporothrix schenckii
Speciile de Trichophyton
Fonseca pedrosoi
Scedosporium
Speciile de Phiolophora
Speciile de
Pneumocystis carinii**
*Date provenind de la MRL, Laboratorul naional de testare pentru fungi i Laboratorul naional de referine micologice
**Pe baza datelor in vivo
Bartizal K. Presented at Antibacterial & Antifungal Drug Discovery & Development Summit. March 2001.
Caspofungin : indicaii
Candidoza sistemic la pacieni neutropenici i nonneutropenici
In plus:
Aspergiloz sistemic la pacieni non-responderi sau
cu toleran sczut la terapia standard
Candidoza esofagian
Candidoza orofaringian
Data on file, MSD.
Empiric
sau
O
O prim
cultur
pozitiv
R
E
Z
U
LT
A
T
ep
c
s
su
tib
il
fluconazol
inhibitor
Voriconazol
sintez
risc de aspergiloz Amphotericin B i.v.
glucan
Caspofungin
Caspofungin C
U
i.v.
re
L
zi
st
T
en
Caspofungin
t
U
sau
R
noi azoli orali
I