Fungi cu importana medicala

Definitie
Fung - o grupare de structuri biotice eucariote,
imobile, unicelulare sau organizate in structuri
pluricelulare

Structura
Celule eucariote
Perete dublu
Capsula Polizaharidica
Membrana plasmatica cu ergosterol
Citoplasma cu mitocondrii, ap Golgi, RE, ribozomi
Nucleu cu nucleol, membrana nucleara

Structura
Parte vegetativa thal

Celule globuloase levuric (fungi levurici) ex Candida

Hifa (filament) --> Miceliu (hife septate sau neseptate mucegaiuri

Parte reproducatoare : Spor + aparat sporal

Spori perfeci (oospori, zigospori, ascospori, basidiospori)
Spori imperfecti (artrospori, blastospori, conidii, aleurii,
chlamidospori)

Multiplicare
Sexuata
Prin inmugurire
Prin diviziune directa (rar)

Diferente intre fungi i bacterii

Kayser, Medical Microbiology 2005 Thieme

All rights reserved. Usage subject to terms and conditions of license .

Fungi (ciuperci)

Dermatofiti dermatophytes

Drojdii yeasts

Mucegaiuri molds

Fungi dimorfi (Histoplasma capsulatum)dimorphic fungi

- se impune analizarea
acestora sub protecia unei hote de securitate
biologic grad III. Plcile cu astfel de culturi se
etaneizeaz obligatoriu cu Parafilm

Candida
albicans is able to form blastospores,
pseudomycelia, true mycelia and chlamydospores. 85
95% of the colonizing vaginal - n premenopausal and
pregnant asymptomatic and healthy women and in
women with acute Candida vaginitis are Candida albicans
Candida glabrata forms only blastospores. more frequent
n postmenopausal, in diabetic and in immunosuppressed
women
C. krusei, C. guilliermondii, C. tropicalis, C. parapsilosis,
Saccharomyces cerevisiae - rare

Infectii fungice
Incidenta infectiilor fungice invazive a crescut dramatic:

Cresterea numarului de pacienti imunodeprimati :

chimioterapii antineoplazice din ce in ce mai agresive

extinderea utilizarii transplantelor de organe
extinderea infectiei HIV

- Extinderea utilizarii procedurilor invazive

Infectii fungice invazive:

- Candida sp = 70%
- Aspergillus sp = 30%

Candida sp : locul 4 in etiologia infectiilor nosocomiale

Candida

ANTIFUNGICE - clasificare
CLASA

DCI

SPECTRU

TOXICITATE

POLIENE

Amfotericina B, iv
(Fungizone, AmBisome)

Spectru ultra-larg:
Candida sp
Criptococcus
Aspergillus
Histoplasma

Nefrotoxicitate
Rash
Greata
Flebita de cateter

ANALOGI
NUCLEOZIDICI

5-fluorocitozina po,iv
(Ancotil)

Candida sp
Criptococcus

Hematologica
Hepatica

AZOLI

Ketoconazol (Nizoral) topic, po

Miconazol (Daktarin) topic
Fluconazol (Diflucan) po, iv
Itraconazol (Orungal,Sporanox) po
Voriconazol (Vfend), po, iv
Posaconazol (Noxafil), po

Candida sp
Crisptococcus
Histoplasma
Blastomyces
Aspergillus
(Itra / Vorico)

Hepatica

CANDINE

Caspofungin (Cancidas), iv
Micafungin (Mycamine), iv
Anidulafungin (Eraxis, Ecalta), iv

Candida sp
Aspergillus

Hepatica

ALTELE

Griseofulvina, po
Terbinafina, po / topic
Sulfura de seleniu (Selsun), topic

Dermatophytes
Pitiriazis verzicolor

ANTIFUNGICE
mecanisme de actiune comparative
TINTA

MECANISM

EFICACITATE

TOLERANTA

Amfotericina B

Membrana
plasmatica

Legare de
ergosterol
Permeabilizare
Moarte celulara

Activitate antifungica
puternica
Spectru larg

Legare de
colesterolul
celulei umane
Nefrotoxiciate

Azoli

Membrana
plasmatica

Inhiba C14-alfademetilaza
Depletie in
ergosterol
Acumulare de
steroli toxici

Activitatea anti- Efecte reduse

fungica
aspra celulei
variabila
umane
Spectru
variabil

Absenta
toxicitatii

Inhiba sinteza
beta (1,3) D
glucan

Activitate
antifungica
puternica

Nu actioneaza
pe celulele
umane

Caspofungin

Perete

ANTIFUNGICE
mecanisme de actiune
-1,6-glucan

Perete
Cell.
Fungic
-1,3-glucan
Strat dublu fosfolipidic al
membranei
celulare fungice

nucleu

AMFOTERICINA B
&
AZOLI

-1,3-glucan sintez
INHIBITOR SINTEZ GLUCAN
(CASPOFUNGIN)

Ergosterol

5 - FLUOROCITOZINA

ANTIFUNGICE - spectru
CASPO

FLU

ITRA

VORICO

AMF B

5 FC

C.albicans

C.tropicalis

C. parapsilosis

C.glabrata

C.krusei

C.lusitaniae

Aspergillus sp

0
+
+
+ fungistatic

Cryptococcus

+ fungicid

Slavin C. Intern Med J. 34:192-200, 2004

Cryptococcus
Cryptococcus neoformans
- criptococoza: asimptomatica, latenta sau clinic manifesta: meningita,
meningoencefalita,
pneumonie

imunodeprimati:
HIV/AIDS,
posttransplant, postterapie citostatice n neoplazii

Tuse, febra, dureri toracice, dureri de cap, greata, varsaturi, fotofobie, confuzie,
tulburari mentale

NU ESTE CONTAGIOASA (nu se transmite de la un individ la altul)

Fungii exista n sol, aer

Detectie de antigen n snge n forma silentioasa, precoce sau n LCR

Factori de virulenta: capsula, producerea de melanina

Alte specii: C. gattii, C. albidus

Se estimeaza ca pe plan mondial sunt cca 1 milion de

cazuri de meningita cu Cryptococcus la pacieni cu HIV*

Figure 1: global burden of HIV-related cryptococcal meningitis, Adapted from BJ Park et al., AIDS 2009;23:525-530
https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html
*Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden
of cryptococcal meningitis among persons living with HIV/AIDS. Aids. 2009 Feb 20;23(4):525-30.

Cauza de mortalitate n Africa

subsahariana

Figure 2: causes of death in sub-Saharan Africa, excluding HIV/AIDS Adapted from BJ Park et al., AIDS 2009;23:525-530
https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html

Cryptococcus
Cryptococcus neoformans
Tratament

n formele asimptomatice i uoare: cu Fluconazol

n formele severe: amphotericin B in combinatie cu

flucytosine, apoi fluconazole o perioada variabila

Exista ghiduri de tratament

ex.http://www.idsociety.org/uploadedfiles/idsa/guidelines-patient_care/
pdf_library/cryptococcal.pdf

https://en.wikipedia.org/wiki/Cryptococcus#/media/File:Cryptococcus.jpg

12

10

Coloana 1
Coloana 2
Coloana 3

0
Rndul 1

Rndul 2

Rndul 3

Rndul 4

By Photo Credit:Content Providers(s): CDC/Dr. Leanor Haley - This media comes from the Centers for Disease Control and Prevention's Public
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credit authors and content providers.English | Slovenina | +/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=754066

Aspergillus
Este un mucegai (mold)
Se cunosca 180 specii de
Aspergillus
< 40 produc infectii la om.
Aspergillus fumigatus
principala specie de
interes medical
Alte specii: A. flavus, A.
terreus, A. niger

Manifestari clinice

Aspergiloza bronhopulmonara alergica,

Sinuzita alergica aspergilozica

Aspergilomul (pulmonar, sinusal) - fungus ball

Aspergiloza pulmonara cronica cavitara cu sau

fr aspergiloame

Aspergiloza invaziva pulmonar i n alte organe

Aspergiloza cutanata

Produse patologice

Sputa

Aspirat bronsic

Biopsie pulmonara

Hemocultura

Tratament

n formele alergice ITRACONAZOL +corticoizi

n formele invazive VORICONAZOL sau
caspofungin, micafungin si posaconazol +
reducerea sau intreruperea medicatiei cu
corticosteroizi
Uneori chirurgical pt indepartarea fragmentului
de esut/organ afectat

Exista ghiduri de tratament: http://www.idsociety.org/uploadedFiles/IDSA/GuidelinesPatient_Care/PDF_Library/Aspergillosis.pdf

A aprut Rezistenta la azoli