Svampinfektioner
Klinik, riskfaktorer och diagnostik
Lena Klingspor
Överläkare/Docent i klinisk Mykologi
Laboratoriemedicin
Karolinska Institutet
Karolinska Universitetssjukhuset
Research projects in Clinical Mycology
Epidemiology studies
- Candida
- Aspergillus
- Fusarium
Evaluating diagnostic methods in different patients groups
- Direct microscopy, Cultures, Antibodies, Antigens, PCR
Developing and clinically evaluating fungal molecular
methods in patients
 PCR-ELISA (Candida and Aspergillus)
 Pyrosequencing (Candida)
 Real-time PCR (Candida and Aspergillus)
 Ongoing project (DNA extraction from tissue/PCR and sequencing
Svampar som orsak till sjukdom
 Mikrobiologi:Terminology and morfologi
 Svampar som orsakar infektion .
Candida
Aspergillus
Zygomyceter(Mukormykos)





Epidemiologi
Riskfaktorer
Diagnostik
Resistens
Behandling
Lena klingspor
Characteristics: Pro->< Eu-karyot
Bacteria
Yeast
Mold
Uni-cellular
Uni &multicellular
multicellular
0,5-2 um
2-12 um
2-500 um
Cell-division
Budding
Conidia & spores
Asexual
Asexual/Anamorph
Asexual /Anamorph
Sexual/Telemorph
Sexual /Telemorph
Biochemical
identification
Morphologic
identification
Biochmical
identification
Nomenklatur Yeast and Moulds
Yeast:
•Yeast cell= blastoconidia= (blastospor)
•Pseudohyphae /hyphae
•Many hyphae= Mycelium
•Moulds
•Conidia=conidiospore
•Hyphae (septated or not)
Namn Efternamn
24 maj 2013
5
http://www.doctorfungus.org
Candida species
• Genus/Species: Candida species
• Slide Reference #: GK 087
• Image Type: Microscopic Morphology
• Disease(s): Candidiasis
Lena Klingspor MD, PhD, BsC.
http://www.doctorfungus.org
Candida albicans
• Genus/Species:
• Image Type:
• Legend:
Candida albicans
Microscopic Morphology
• Title:
• Disease(s):
Yeast in oral scraping
Candidiasis
Yeast cells and pseudohyphae in material from the oral cavity, KOH preparation,
Lena Klingspor MD, PhD, BsC.
phase-contrast microscopy.
http://www.doctorfungus.org
Aspergillus fumigatus
• Genus/Species:
• Image Type:
• Legend:
Aspergillus fumigatus
Microscopic Morphology
• Title:
• Disease(s):
Hyphae in cytopathology specimen
Aspergillosis
Dichotomously branching hyphae. GMS stain, sputum, 400X.
Lena Klingspor MD, PhD, BsC.
http://www.doctorfungus.org
Aspergillus fumigatus
• Genus/Species: Aspergillus fumigatus
• Image Type:
Microscopic Morphology
• Legend:
• Title: Hyphae in sputum
• Disease(s):
Aspergillosis
Aspergillus hyphae in sputum, KOH preparation, phase contrast microscopy.
Lena Klingspor MD, PhD, BsC.
Svampar som sjukdomsorsak
 Allergi
 Förgiftning = toxikos
 Infektion = mykos
Svampar som kan ge upphov till
infektioner
Dermatofyter - tex Trichophyton
Jästsvampar – tex Candida
Mögelsvampar – tex Aspergillus
Dimorfa svampar – tex. Histoplasma
Invasiva Svampinfektioner (ISI)
De vanligaste ISI i Sverige är jäst och mögelsvampsinfektioner (opportunistiska infektioner) orsakade av:
Candida
Aspergillus
Kryptokocker
Mindre vanligt förekommande:
Trichosporon
Mukormykos (Zygomykos)
Malassezia
Hyalohyphomykos
Saccharomyces
Phaeohyphomykos
(Endemiska svampar)
Svamppatogener som orsak till infektion
Neonataler
Candida
Malazessia
(Aspergillus
Zygomycetes)
Allogena HSCT
Candida
Aspergillus
Fusarium
Zygomycetes
Kirurgpatients
Candida
Leukemi
Candida
Aspergillus
Zygomycetes
Lungtransplantation
Aspergillus
Candida
HIV
Candida
Cryptococcus neoformans
Penicillium marneffei (SE Asia)
Levertransplantation
Candida
Aspergillus
IV.drogmissbrukare /Diabetes
Candida
(Zygomycetes)
Varför får man svampinfektion?
Balansen rubbas mellan svampen och värdorganismen
Värdens försvar
Svamp
MILJÖN

Adapted from the Mycology Initiative
Ytliga mykoser
•
Dermatomykos = Svampinfektion i huden
 Dermatofyt
 Jästsvamp
Candida
Malassezia (Pityriasis versicolor)
•
Onychomykos = Svampinfektion i nageln
 Dermatofyt
 Candida
 Mögel
Dermatofyter (trådsvampar)
 Beroende av keratin (hornämne)
 Angriper: Hud, hår och naglar
 Ytliga infektioner –benämns Tinea
019
Jästsvamp
Candida
Infektioner oftast endogena
I normalfloran: hud, mag-tarmkanalen,
orofarynx, vagina
Hud-, nagel- och slemhinneinfektioner
Candida vulvovaginit
 Orsakas oftast av C.albicans
 Ca 75% av kvinnor drabbas minst en gång i livet
 40-50% drabbas ytterligare en gång
 Återkommande vulvovaginal candidos (flera ggr/år)
är ett stort problem för de kvinnor som drabbas
(kräver gynekologisk specialistvård)

Lena Klingspor MD,
Vanligt förekommande
Candida arter
C. albicans
C. glabrata
C. parapsilosis
C. guilliermondii
Sacharomyces cervisiae
C.dubliniensis
C.krusei
C. tropicalis (Asien)
C. lusitaniae
Orala candidoser
 Akut candidos
 Pseudomembranös
 Erytomatös
 Kronisk candidos
 Pseudomembranös
 Erytomatös
 Candidaassocierade
förändringar
 Hyperplastisk
 Nodulär
 Plackliknande
 Angulär cheilit
 Protesstomatit
 Median romboid glossit
Predisponerande faktorer för orala Candidainfektioner
 Ålder
- nyfödda, åldringar
Generellt
Underliggande sjukdomar- Leukemi, cancer,HIV/ AIDS,
diabetes mellitus, anemi, uremi,r, undernäring.
 Behandling med- Antibiotika, steroider, cellgifter.
 Övrigt:
 Muntorrhet pga läkemedel, strålning eller Sjögrens syndrom
(förändringar i salivens kvalitet)
Lokalt
 Tandproteser, tobaksrökning, ofta förkommande sockerrika
måltider
Symptom
 Förändrad smakförnimmelse
 Sveda speciellt vid erythematös candidos
Pseudomembranös candidos (torsk)
 Förekommer hos spädbarn
Vanligast hos patienter med:
 Immunsuppression
 Diabetes mellitus
 Kortisonbehandling
056
071
Exempel på psedomembranös
candidos
Kliniska fynd
Pseudomembranös Candidos:
 Avskrapbara gråa till vita krämiga plack
 Underliggande epitel är rodnat och
lättblödande
Vanligast lokalisation:
 Munslemhinna, gom och tunga
Erytomatös candidos
Rodnad slemhinna ofta med intensiv sveda
Vanligaste lokalisationen:
 Hårda gommen, kindslemhinnan och
tungryggen
057
058
059
Kronisk hyperplastisk: Vita, ej avskrapbara,
vanligen symptomfria slemhinnehyperplasier
Vanligaste lokalisationen:
 den anteriora buccala mucosan
Kronisk nodulär: Vita, knappnålsstora, ej
avskrapbara och vanligen ej symptom-givande papler
Kronisk plackliknande: Vita, ej avskrapbara plack
Differential Diagnostik
 Lichen, vita ej avskrapbara stråk på främst
kindslemhinna
 Leukoplaki, vit enstaka fläck , ej avskrapbar. Ingen
känd orsak
 Lingua geografica normalvariant på tungan . Ej
avskrapbar.
Lichen
Lichen
Leukoplaki
Lingua geografica
Herpes
Vanligt förekommande
Candida arter
C. albicans
C. glabrata
C. parapsilosis
C. guilliermondii
Sacharomyces cervisiae
C.dubliniensis
C.krusei
C. tropicalis (Asien)
C. lusitaniae
Diagnostik




Klinik
Direktmikroskopi
Odling och typning
Biopsi/skrapprov för histologisk undersökning
082
Artidentifiering av Candida
Serumtest
092
Lena klingspor

BICHRO-DUBLI FUMOUZE® - Coagglutinaton test

C. dubliniensis
C. albicans
078
Antifungal drugs
1950
Griseofulvine
First azols
19900
Fluconazole
Itraconazole
Terbinafine
Lipid-Amph B
Namn Efternamn
1960
Amphotericin B
Miconazole
Clotrimazole
Flucytosine
2000
Caspofungin
Voriconazole
Posaconazol
Anidulafungin
Micafungin
1970
Econazole
Miconazole (IV)
1980
Ketoconazole
(po)
On the way
Ravuconazol
Sordarins...
24 maj 2013
47
Tabell I. Probable in vitro-suceptibility for yeasts
Species
Amfotericin B Echinocandins Fluconazole posaconazole Voriconazole Itraconazole
C. albicans
S
S
S
S
S
S
C. glabrata
S
S/R
I/R
I/R
I/R
I/R
C. parapsilosis
S
I/R
S/R
S
S
S
C. tropicalis
S
S
S
S
S
S
C. lusitaniae
S/I
S
S
S
S
S
C. krusei
S
S
R
I/R
I/R
I/R
C. neoformans
S
R
S/I
S
S
S
S/R
R
S
S
S
S
Trichosporon spp.
Probable in vitro suceptibility for yeasts

C. glabrata and C. krusei , C. inconspicua, C.lambica, C.
norvegensis, C.famata and some other spp have naturaly
decreased susceptibility or are resistant to fluconazole
 Echinocandins (caspofungin, anidulafungin, micafungin)
has no in vitro-aktivitet against Cryptococcus-, Malassezia-,
Trichosporon- och Rhodotorula-species and some other spp..
 C. parapsilosis and C. guilliermondii has no break-points
because they are bad targets for treatment with echinocandins .
Lena klingspor
Behandling av oral
candidos
1) Avlägsna (om möjligt) predisponerande faktorer
2) God munhygien inklusive tandproteshygien
Tandprotes: klorhexidin, nystatin
Oral svamp infektion
Medel att välja
 Lokala medel:
 Nystatin




Systemiska:
Fluconazol po. (mixtur)
Itraconazol p.o. (mixtur)
Vorikonazol p.o. (mixtur)
Behandling av oral Candidos
 Spädbarn – Nystain (Mycostatin) lösning penslas
i munhålan
 Vuxna - Nystatin Ges i 1-2 veckor
 Vid infekterade munvinkelragader – kräm lokalt
 Vid svår infektion ges systembehandling med
tex. Fluconazole (Diflucan) 7-14 dagar
Fluconazole (Diflucan®)
 i.v., oral (suspension & kapslar)
 Spektrum
Ineffektiv mot vissa non-albicans
stammar s.s. C. krusei & glabrata
Användbar vid känsliga arter som
C. albicans
Systemmykoser
 Djupa infektioner – blodförgiftning
inre organ angrips
 Viktigt att rätt diagnos ställs
RISKGUPPER: SYSTEMISK SVAMP INFEKTION
Neutropeni
&
HSCT
IVA
Lever
HIVInvasiv
svampinfektion
Lunga
CGD
Hjärta
Bränn
skador
Njur
Solid organ
Transplantion
Riskfaktorer för ISI.
1. Immunosuppression
Kemoterapi
Radioterapi
Korticosteroider
2. Andra
riskfaktorer
Antibiotika
CVK
Mukosit
TPN/Malnutrition
Svampkolonisation
sjukhusmiljö
Candida
Epidemiologi
Candidemi
ECMM survey of candidaemia in Europe
Sept ‘97 - Dec ‘99
Underlying pathology/medical care of patients with candidaemia
(n=2089)
Surgery
Intensive care
Solid tumour
Steroids
Haematological malignancy
Premature birth
Solid organ transplantation
HIV infection
Burn
No.
%
933
839
471
364
257
125
74
63
29
44.7
40.2
22.5
17.4
12.3
6.0
3.5
3.0
1.4
Some patients had more than one underlying pathology/medical care
Tortorano et al EJCMID 2004; 23: 317-23
Survey Candidemia in Sweden 2005-06

Nationwide, Laboratory-base

The annual incidence of candidemia in Sweden is 4.5 cases per 100,000
inhabitants (minimal estimate).

The incidence vary between age groups. More than 75% of episodes
occurred in patients >50 years old.

Candidemia occured more often (56% of episodes) in males.

Candidemia was most often associated with gastrointestinal surgery and
intensive care treatment

C. albicans remains the most common cause of candidemia in Sweden. The
second most common species is C. glabrata. The prevalence of C. glabrata
rises with increasing patient age.

Ericsson J,et al. Clin Microbiol Infect. 2012

Patients
Age(y)
N
< 1
1-20
21-40
41-60
61-80
81-
21
18
22
92
175
61
Total
389

%
5.4
4.6
5.7
23.7
45.0
15.7
Female
Male
6
8
15
53
73
26
15
10
7
39
102
35
181
208

Predisposing factors
Referring clinics
%
ICU
Surgery
General medicine
Infection
Neonatal/Pediatric
Hematology
Oncology
Gastroenterology
Urology
Gynecology
Transplantation
Neurology
Other
Total
No of patients
126
89
40
23
21
20
14
12
9
8
3
3
17
389
%
32.4
22.9
10.3
5.9
5.4
5.1
3.6
3.1
2.3
2.1
0.8
0.8
5.7

Distribution of yeast species
Species
No of isolates
C. albicans
C. glabrata
C. parapsilosis
C. dubliniensis
C. tropicalis
C. lusitaniae
C. krusei
C. pelliculosa
S. cerevisiae
Geotrichum capitatum
Malassezia pachydermatis
Rhodotorula mucilaginosa
243
81
36
15
8
8
5
1
1
1
1
1
Total
401
%
60.6
20.2
9.0
3.7
2.0
2.0
1.2
0.2
0.2
0.2
0.2
0.2

Conclusions 1
 The estimated coverage of confirmed candidemia
cases during the study period was >99%.
 The annual incidence of candidemia in Sweden is
4.5 cases per 100,000 inhabitants (minimal estimate).
 The incidence vary between age groups. More than
75% of episodes occurred in patients >50 years old.
 Candidemia occured more often (56% of episodes)
in males.
Conclusions 2
 Candidemia was most often associated with
gastrointestinal surgery and intensive care treatment.
 C. albicans remains the most common cause of
candidemia in Sweden. The second most common
species is C. glabrata. The prevalence of C. glabrata
rises with increasing patient age.
Klinik och diagnostik
Akut disseminerad candidos (ADC)
 Vanligen ospecifika symtom:
 antibiotikarefraktär feber
 ev. svår sepsis, ev. med chock
 Flera organ kan drabbas, t.ex.:
 ögon (endoftalmit/chorioretinit)
 hud
 njurar
 lungor
 hjärta (endokardit)
 skelett
 CNS
Diagnostiska metoder
 Direkt mikroskopi
 Odlingar
 Histopatologi
 Serologi : antigen och antikroppstester
 Metaboliter (D- och L-arabinitol i urin)
 Molekylärbiologiska metoder
Klinik och diagnostik – Candidos
Akut disseminerad candidos (ADC), forts.
 Diagnostik
upprepade blododlingar
ultraljud
CT (computed tomography)
MR (magnetic resonance imaging
tomography)
biopsi
ögonundersökning
http://www.doctorfungus.org
Candida albicans
• Genus/Species:
• Image Type:
• Legend:
Candida albicans
Macroscopic Morphology
• Title:
• Disease(s):
Yeast colonies
Candidiasis
Yeast colonies. Sabouraud glucose agar, 25C.
Lena Klingspor MD, PhD, BsC.
Artidentifiering av Candida
Serumtest
085
Maldi TOF
• New techniques like Matrix-assisted laser desorption/ionization (MALDI)
is a soft ionization technique used in mass spectrometry, allowing the
analysis of biomolecules (biopolymers such as proteins)
• The type of a mass spectrometer most widely used with MALDI is the
TOF (time-of-flight mass spectrometer)
• Maldi TOF has not so far proved to be sensitive enough for
detecting Candida directly in blood or tissue
Namn Efternamn
24 maj 2013
72
MALDI Biotyper
 Classifications of organisms that can be analyzed: Bacteria,
yeast, molds, mycobacteria
 From cultures one colony of yeast for identifucation
 Large, library with >3900 microbial strains in library
representing >2000 species. Continuosly updated!
 ADDITIONAL ANALYSES: Direct from biofluids such as
urine and positive blood culture
Lena klingspor
MALDI-TOF MS microorganism identification
Identified species
Data interpretation
Generate MALDI-TOF
profile spectrum
Prepare onto
a MALDI target plate
Select a colony
Unknown
microrganism
?
Goslar, 09/10/2007
Procedure Overview – Simple & Easy

Prepare Smear

20 min.

Hybridize

30 min.
• Add drop from BC+
• Add PNA probe
• Fix bacteria/yeast onto
slide
• Probe enters cells and
binds to target rRNA
sequence, if present
• Heat
• Methanol, or
• Flame fixation

Wash

30 min.
• Immerse slide in Wash
Solution
• Unbound and excess
PNA probe removed
from cells and slide

Examine

2 min.
• Fluorescence
microscopy using 60x
or 100x oil objective
• Target bacteria/yeast
fluoresce
Yeast Traffic Light® PNA FISH®
C. albicans/C.glabrata PNA FISH®
C. albicans 
C. parapsilosis

C.
C. glabrata
tropicalis C. krusei
C. albicans
C. glabrata
PNA FISH
Peptid Nucleic Acid= PNA
Fluorecence In Situ Hybridisering= Fish
Real-time Fungal PCR assay was developed
and established June 2002 at Huddinge
DNA extraction
Chemical + Mechanical disruption + Automatic extraction (MagNaPure LC)
For measuring the DNA concentration
NanoDrop ND-1000 Spectrophotometer
Selection of target :Multicopy gene; 18S rRNA gene
Real-Time PCR
LightCycler 2.0
Klingspor L and Jalal S. Clin Microbiol Infect.
2006:12(8): 745-53.
R-T Fungal PCR assay
A method for detection of Candida and Aspergillus DNA
•
in EDTA-blood and plasma samples
•
body fluids such as BAL, CSF, bile, pleura, ascites
•
in biopsy specimens.
R-T Fungal PCR assay with hybridisation probes
Provides rapid (6 h) and sensitive (2-10 genome) detection of
•
Aspergillus and Candida to genus level *
•
Identification of Candida and Aspergillus to species level
with sequencing
•
Identification of other Yeasts and Molds with sequencing
*Klingspor L ,Jalal S. Clin Microbiol Infect 2006; 12:745-753
Aspergillus
95% orsakas av
A.fumigatus A.flavus och A.niger
The clinical spectrum of conditions resulting from inhalation of aspergillus spores
 ICH, immunocompromised host; IPA, invasive pulmonary aspergillosis; ABPA, allergic
bronchopulmonary aspergillosis.

Zmeili, O.S. et al. 2007
Reprinted by permission from Soubani and
(Chest 2002;121:1988-1999).
Namn Efternamn
Chandrasekar
24 maj 2013
82
Vilka drabbas?
Kliniska tillstånd
Lung ± hjärt transplant
range (%)
19-26
Lever transplant
1.5-10
Njur transplant
0.5-10
Allogen HSCT
4-9
Autolog HSCT
0.5-6
INVASIVE ASPERGILLOSIS AND UNDERLYING DISEASE
Denning Clin Infect Dis 2001 26 pp781-805
Systemisk fungal infektion Aspergillus







Huvudsakligen A. fumigatus
Icke endogen flora
Sporer inhaleras – reduceras med LAF
Bihåle och lunginfektion
Positiva blododl ytterst sällan
CNS-infektion förekommer
Abdominal-infektion mindre vanlig
Imaging
 Nodule surrounded by ground glass appearance
 due to infiltration/invasion of adjacent lung tissue
 Very nonspecific
 Other fungi
 Aspergillosis, fusariosis, zygomycosis, candidosis,
coccidiodomycosis
 Other infection
 TB, nocardia, organizing pneumonia, septic
emboli
 Malignancy
 angiosarcoma, choriocarcinoma, osteosarcoma,
Kaposi’s
 Vasculitides, eosinophilic lung disease
029
Brain abscess
Diagnostiska metoder
 Direkt mikroskopi
 Odlingar
 Histopatologi
 Serologi: antigen och antikropps tester
 MOLEKULÄRBIOLOGISKA METODER
Fluorescent brighteners such as Blankophor, increase
sensitivity and speed
(BAL, sputum, pleura fluid, tracheal fluid, wounds,biopsies)
037
Artidentifiering Aspergillus
Lena Klingspor MD, PhD, BsC.
038
Lena Klingspor MD, PhD, BsC.
041
Lena Klingspor MD, PhD, BsC.
033
Open-lung biopsy specimen showing Aspergillus acute branch hyphae Invading
a blood vessel causing thrombus formation (Methenamine silver/GMS stain)
Zmeili, O.S. et al. 2007
034
Viktigtt!
Konventionell Histopatologi kan inte skilja
mellan Aspergillus,
Fusarium och Scedosporion spp!!
Kombinera med odling av
BIOPSIES
och/eller Immunohistokemi*!
och/eller PCR/sekvensering
(för att öka känligheten och specificiteten)
*Jensen HE, et al. J Pathol. 1997
Culture
May give a definitive diagnoses
Interpretation may be difficult, especially isolates
from airways and sinus.
Aspergillus is very rarely isolated from blood,
urine or CSF
Aspergillus can somtetimes be isolated from wounds.
Invasive Aspergillus infection
Culture from:
•
•
•
•
BAL
Sinus
Cutaneous (in children)
Biopsies
may give definite diagnosis
Non-culture methods
Aspergillus









MOLECULAR METHODs
Real-Time PCR
Sequencing
SEROLOGY : antigen (and antibody tests)
Platelia ®Aspergillus antigen test (galactomannan)
Serum,BAL och likvor
Fungitell ® /Glucatell ® (1-3) Beta-D-Glukan
Serum
ECIL: PCR recommendations
The current status of the technical and clinical validation of
PCR for Aspergillus in blood and other fluids does not
currently allow for a recommendation for clinical use.
The technical recommendations of the European Aspergillus
PCR Initiative (EAPCRI) for processing aspergillus PCR have
been published after the ECIL 3 meeting and are those
recommended by ECIL
Aspergillus PCR: one step closer towards standardisation
L White, S Bretagne, L Klingspor, WJG Melchers, E McCulloch, B
Schulz, N Finnstrom, C Mengoli, RM Barns, JP Donnelly, J Loeffler
J Clin Microbiol,. 2010
Namn Efternamn
24 maj 2013
101
R-T Fungal PCR assay with hybridisation probes
Provides rapid (6 h) and sensitive (2-10 genome) detection of
•
Aspergillus and Candida to genus level *
•
Identification of Candida and Aspergillus to species level with sequencing
•
Identification of other Yeasts and Moulds with sequencing
*Klingspor L ,Jalal S. Clin Microbiol Infect 2006; 12:745-753
Diagnosis of Fungal (IA) infection is difficult
Contact the Mycology laboratory!
BAL
Direct microscopy (DM)
culture, galactomannan antigen (GM) test
DNA extraction, R-T-PCR ( and sequencing )
Trachel/bronchial ,sputum , sinus aspirates and biopsies
DM, culture and PCR (sequencing) and histopathology of
biopsies
If Aspergillus is grewing :Typing to species level should be
performed as well as suceptibility testing (EUCAST)
Lena klingspor
Resistance in Aspergillus: An emergent problem?!
 In patients after long term treatment
 Naïve patients
Azole resistance in A. fumigatus may be restricted to
itraconazole or involving cross-resistance to other tri-azoles
has been associated with a number of hot spots in the erg
11/cyp5 A gene
 Caspofungin resistance in A. fumigatus has been reported
whithout or with mutations in the FKS1 gene
 Amphotericin B resistance can be seen in :
Aspergillus terreus and occasionally Aspergillus flavus
Arendrup M, et al. Antimicrob Agents Chemother. 2009
Tabell II. Probable in vitro-antimycotic suceptibility for moulds
Species
Aspergillus fumigatus
Amfotericin B Voriconazole posaconazole
Itraconazole
Fluconazole
Echinocandins
S
S/R
S/R
S/R
R
S/R
A. flavus
S/I
S
S
S
R
S
A. niger
S
S/I
S/I
S/I
R
S
A. terreus
R
S
S
S
R
S
Zygomyceter*
S
R
S/I
I/R
R
R
R
R
R
R
Fusarium solani
F. oxysporum
Scedosporium apiospermum
Scedosporium prolificans
S/R
S
I/R
I/R
R
R
R
S/R
S/R
S/R
R
R
R
R
R
R
R
R
R
*Zygomycetes: Rhizopus-, Mucor-, Rhizomucor- och Absidia-species.
In vitro-suceptibility is written S (probably susceptible), I (raised MIC-value) and R (in vitro-resistant). Observe that
clinical break points for moulds are missing except for A. fumigatus.
Lena klingspor
Systemisk Zygomykos (Mukormykos)
Involverar framför allt
• Rhino-facial-cranial området
• Gastrointestinal trakten,
• Huden
Har en förkärlek att invadera arteriella blodkärl, orsakande
emolisering och nekros av omgivande vävnad
Distribution: Global
Aetiological Agents: inkluderar arter som Rhizopus, Mucor,
Absidia, Cunninghamella, Saksenaea and Mortierella.
Smittvägar
 Inhalation av luftburna sporer
 Kutan inokulering
 Intag av kontaminerad föda
Systemisk Zygomykos
Predisponerande faktorer
•
•
•
•
•
•

Hematologiska maligniteter
Diabetes
Neutropeni
Kemoterapi och kortisonbehandling
HSCT och organtransplantation
Intravenöst missbruk
Zygomykos
• Okontrollerad diabetes (ketoacidos)
• Steroidinducerad hyperglykemi
• Hematologiska maligniteter
• Allogen HSCT
• HIV
• Intravenöst missbruk
• Kutan zygomykos (brännskada)
Zygomykos
 En retrospektiv studie
inkluderade 929 patienter
 Medelålder: 38,8 år, Män :65%
 Mortalitet
• Diabetes 44%
• Malignitet 66%
• Disseminerad infektion 96%
Roden M, et al. CID 2005
Diagnostik
•Mikroskopi:
Förekomst av icke-septerade hyfer i material från
nekrotiska lesioner, sputum, gomskrap eller BAL
är synnerligen signifikant.
• Odling:
Från näsa, gom, sputum och BAL.
Odling från biopsi ger säkrast diagnos.
• Histopatologi
• Datortomografi
http://www.doctorfungus.org
Saksenaea vasiformis
• Genus/Species: Saksenaea vasiformis
• Slide Reference #: GK 574
• Image Type: Histopathology
• Disease(s): Subcutaneous
zygomycosis (Mucormycosis)
485
Diagnostik DT
Multipla (≥10) nodulae och pleuravätska
talar för Pulmonell zygomykos
Chamilos et al, CID 2005;41:60-6
Diagnostik DT
 Multipla (≥10) nodulae och pleuravätska
 talar för Pulmonell zygomykos

Chamilos et al, CID 2005;41:60-6
479
482
483
472
Sequencing
•
Identification of ZYGOMYCETES (Mucormycosis)
such as Rhizopus spp.
*Klingspor L ,Jalal S. Clin Microbiol Infect 2006; 12:745-753
Behandling
Om möjligt utsätt immunosuppresiv behandling och
korrigera riskfaktorer
Avlägsna all infekterad vävnad
Adekvat antimykotika
Adjuvant behandling
Tabell II. Probable in vitro-antimycotic suceptibility for moulds
Species
Aspergillus fumigatus
Amfotericin B Voriconazole posaconazole
Itraconazole
Fluconazole
Echinocandins
S
S/R
S/R
S/R
R
S/R
A. flavus
S/I
S
S
S
R
S
A. niger
S
S/I
S/I
S/I
R
S
A. terreus
R
S
S
S
R
S
Zygomyceter*
S
R
S/I
I/R
R
R
Fusarium solani
S/R
R
R
R
R
F. oxysporum
Scedosporium apiospermum
Scedosporium prolificans
S
I/R
I/R
R
R
R
S/R
S/R
S/R
R
R
R
R
R
R
R
R
R
*Zygomycetes: Rhizopus-, Mucor-, Rhizomucor- och Absidia-species.
In vitro-suceptibility is written S (probably susceptible), I (raised MIC-value) and R (in vitro-resistant). Observe that
clinical break points for moulds are missing except for A. fumigatus.
Lena klingspor
TACK!