Svampinfektioner

Klinik, riskfaktorer och diagnostik

Lena Klingspor Överläkare/Docent i klinisk Mykologi Laboratoriemedicin Karolinska Institutet Karolinska Universitetssjukhuset

Research projects in Clinical Mycology - - 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

Candida

Aspergillus Zygomyceter(Mukormykos) Epidemiologi Riskfaktorer Diagnostik Resistens Behandling

infektion

. Lena klingspor

Characteristics: Pro->< Eu-karyot

Bacteria

Uni-cellular 0,5-2 um Cell-division Asexual Biochmical identification

Yeast

Uni &multicellular

Mold

multicellular 2-12 um Budding 2-500 um Conidia & spores Asexual/Anamorph Asexual /Anamorph Sexual/Telemorph Sexual /Telemorph Biochemical identification Morphologic 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

Candida

species

•

Genus/Species:

Candida

species •

Image Type:

Microscopic Morphology •

Slide Reference #: GK 087

•

Disease(s):

Candidiasis Lena Klingspor MD, PhD, BsC.

Candida albicans

•

Genus/Species:

Candida albicans

•

Title:

Yeast in oral scraping •

Image Type:

Microscopic Morphology •

Legend:

•

Disease(s):

Candidiasis Yeast cells and pseudohyphae in material from the oral cavity, KOH preparation, phase-contrast microscopy. Lena Klingspor MD, PhD, BsC.

Aspergillus fumigatus

•

Genus/Species:

Aspergillus fumigatus

•

Title:

Hyphae in cytopathology specimen •

Image Type:

Microscopic Morphology •

Legend:

•

Disease(s):

Aspergillosis Dichotomously branching hyphae. GMS stain, sputum, 400X.

Lena Klingspor MD, PhD, BsC.

Aspergillus fumigatus

•

Genus/Species:

Aspergillus fumigatus

•

Title:

Hyphae in sputum •

Image Type:

Microscopic Morphology •

Legend:

•

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 ä r j ä st och m ö gelsvamps infektioner (opportunistiska infektioner) orsakade av:  Candida  Aspergillus  Kryptokocker Mindre vanligt f ö rekommande: Trichosporon Mukormykos (Zygomykos ) Malassezia Saccharomyces Hyalohyphomykos Phaeohyphomykos (Endemiska svampar)

Svamppatogener som orsak till infektion Neonataler Candida Malazessia (Aspergillus Zygomycetes) Kirurgpatients Candida Lungtransplantation Aspergillus Candida Levertransplantation Candida Aspergillus Allogena HSCT Candida Aspergillus Fusarium Zygomycetes Leukemi Candida Aspergillus Zygomycetes HIV Candida Cryptococcus neoformans Penicillium marneffei (SE Asia) IV.drogmissbrukare /Diabetes Candida (Zygomycetes)

Varför får man svampinfektion?



Balansen rubbas mellan svampen och värdorganismen Svamp Värdens försvar 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, PhD, BsC.

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 Kronisk candidos  Candidaassocierade förändringar          

Pseudomembranös Erytomatös Pseudomembranös Erytomatös

Hyperplastisk Nodulär Plackliknande

Angulär cheilit

Protesstomatit Median romboid glossit

Predisponerande faktorer för orala Candida infektioner



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

 ® 

C. dubliniensis

 

C. albicans

078

Antifungal drugs



1950

 Griseofulvine  First azols 

1990 0

 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) 

Ravuconazol



Sordarins

... 24 maj 2013

47

Tabell I. Probable in vitro-suceptibility for yeast s

Species C. albicans C. glabrata C. parapsilosis C. tropicalis C. lusitaniae Amfotericin B Echinocandins Fluconazole posaconazole Voriconazole Itraconazole S S S S S / I S S/ R I/R S S S I/R S/ S S R S I/R S S S S I/R S S S S I/R S S S C. krusei C. neoformans Trichosporon spp. S S S/R S R R R S/I S I/R S S I/R S S I/R S S

Probable in vitro suceptibility for yeast s 

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

 

Invasiv



svampinfektion



CGD



Lunga



Hjärta

 Solid organ  Transplantion 

Bränn skador



Njur

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 44.7 839 40.2 471 22.5 364 17.4 257 12.3 125 6.0 74 3.5 63 3.0 29 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)  < 1  1-20  21-40  41-60  61-80  81-  Total  N % Female Male 21 18 22 92 175 61 5.4 6 4.6 8 5.7 15 23.7 53 45.0 73 15.7 26 15 10 7 39 102 35 389 181 208



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 

C. albicans



C. glabrata



C. parapsilosis



C. dubliniensis



C. tropicalis



C. lusitaniae



C. krusei



C. pelliculosa



S. cerevisiae



Geotrichum capitatum



Malassezia pachydermatis



Rhodotorula mucilaginosa

 Total No of isolates 243 81 36 15 8 8 5 1 1 1 1 1 401 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

Candida albicans

•

Genus/Species:

Candida albicans

•

Title:

Yeast colonies •

Image Type:

Macroscopic Morphology •

Legend:

Yeast colonies. Sabouraud glucose agar, 25C.

•

Disease(s):

Candidiasis 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



Unknown microrganism



?



Generate MALDI-TOF profile spectrum



Prepare onto a MALDI target plate



Select a colony

Goslar, 09/10/2007

 

Procedure Overview – Simple & Easy

Prepare Smear



Hybridize



Wash



Examine



20 min.

• Add drop from BC+ • • • • Fix bacteria/yeast onto slide Heat Methanol, or Flame fixation 

30 min.

• Add PNA probe • Probe enters cells and binds to target rRNA sequence, if present 

30 min.

• Immerse slide in Wash Solution • Unbound and excess PNA probe removed from cells and slide 

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. tropicalis



C. glabrata C. krusei



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 Chandrasekar (Chest 2002;121:1988-1999).

24 maj 2013

82



Vilka drabbas?

Kliniska tillstånd

Lung ± hjärt transplant Lever transplant Njur transplant Allogen HSCT Autolog HSCT

range (%)

19-26 1.5-10 0.5-10 4-9 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)

Resistance in Aspergillus: An emergent problem?!

  In patients after long term treatment Naïve patients 

Azole resistance in

11/

cyp5 A

gene

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

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 A. flavus A. niger A. terreus

Zygomyceter* Fusarium solani F. oxysporum Scedosporium apiospermum Amfotericin B Voriconazole posaconazole

S S/R S/R S/I S R

S S/R S

S S/I S

R I/R

S S/I S

S/I R I/R Itraconazole

S/R

Fluconazole

S S/I S

I/R R R

R R R R

R R R S/R S/R S/R R R Scedosporium prolificans R R R R R Echinocandins

S/R S S S

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.

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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

Saksenaea vasiformis

•

Genus/Species:

Saksenaea vasiformis

•

Image Type:

Histopathology •

Slide Reference #: GK 574

•

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 A. flavus A. niger A. terreus

Zygomyceter*

Fusarium solani F. oxysporum Scedosporium apiospermum Amfotericin B Voriconazole posaconazole S S/R S/R S/I S R

S

S/R S S S/I S

R

I/R S S/I S

S/I

R I/R Itraconazole S/R Fluconazole S S/I S

I/R

R R R R R R

R

R R S/R S/R S/R R R Scedosporium prolificans R R R R R Echinocandins S/R S S S

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.

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TACK!