Wertigkeit der Diagnostik von Pilzinfektionen an der Intensivstation Cornelia Lass-Flörl Division für Hygiene und medizinische Mikrobiologie MUI Innsbruck
Key message... 1. Surveillance-Kulturen spielen eine untergeordnete Rolle in der Diagnosesicherung. 2. Blutkultur ist der Goldstandard. 3. Non-albicans Candida nehmen zu. 4. Resistenzen gegen Azole nehmen zu. 5. Breakpoints fehlen-wertigkeit von MHK noch unklar.
Maschmeyer 2007, Ruhnke 2007, Cornely 2007 Patient Types ICU patients oncology patients Candida spp Aspergillus Zygomyzeten Hematological maligancies Bone Marraow Organ transplant Aspergillus spp Zygomyzeten Candida Types of Fungi
Suetens C. et al. J Hosp Inf 2007
Approaches to diagnosis Non-culture methods Culture methods Microscopic examination: direct or histopathology
Type of test Strengths & Weaknesses Reference ANTIBODIES Many are against inadequately characterized CANDIDA Antibodies to Candida ANTIGENS Mannan Undefined heat-labile glycoprotein antigen (CAND-TEC Candida Detection System from Ramco Laboratories, Houston, Texas) Elisa for Candida mannan variable results between the labs Elisa for Candida anti-mannan limited value in the immunocompromised host β-d-glucan Candida enolase METABOLITES D-arabinitol antigenic extracts Non-standardized techniques Seen late in the course of disease Limited use in immunosuppressed patients Sensitivity ~70% Short serum half-life Complicated measurement technique Simple Commercially available Sensitivity and specificity very variable but generally below 60% Testing multiple serum samples increases sensitivity Colonization produces positive results Cross reactivity with multiple fungi Appears sensitive Low sensitivity and specificity Testing multiple serum samples increase sensitivity Higher sensitivity in patients with fungemia and lower when tissue Bognoux et al. Gentry et al. Greenfield et al. Kozinn et al. Fujita et al. Kerkering et al. Bougnoux et al. Escuro et al. Fung et al. Gentry et al. Ness et al. Pieins et al. Miyazaki et al. Obayashi et al. Van Denveter et al. Walsh et al. De Repentigny et al. Walsh et al. S E R O L O G Y P C R invasion has occurred Mannose Costly equipment required Low sensitivity Bougnoux et al. POLYMERASE CHAIN REACTION Universal primers for pathogenic species are available Bougnoux et al. Hopfer et al. Polanko et al.
Culture
Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists Eggimann, 2005
18% 16% 14% 12% 10% 8% 6% 4% 2% 0% 2003 2004 2005 2006 2007 E.coli koag.neg.s. Candida Keim und Resistenzbericht LKI Innsbruck, 2007
Risk factors for invasive Candidiasis 3 antibiotics Antibiotics 4 d Time 4 d in ICU Mechanical ventilation >48 High APACHE II score Abdominal surgery CVC TPN Age Neutropenia Immunosuppression (chemotherapy, steroids, other therapies) Concomitant infection Diabetes mellitus Candida colonization 2 sites Candiduria (>100,000 colonies) APACHE = Acute Physiology and Chronic Health Evaluation. Pappas PG et al. Clin Infect Dis 2004;38:161-189; Ostrosky-Zeichner L et al. Crit Care Med 2006;34:857-63
The diagnostic value of fungal surveillance cultures in critically ill patients COLONISATIONS INDEX 172 patients: oncology center/medical and surgery ICUs, 159 eligible Surveillance cultures: 5 sites, 2 x week 14 pts: IFI NPV: 0.89 PPV: 0.56 Pelz et al. 2006
the Candida Score as predictor of proven candidal infection in critically ill patients Candida Score (1699 ICU patients) Multifocale Candida species colonization Surgery on ICU admission Severe Sepsis Total parenteral nutrition A score of > 2.5 selects patients for tretament Leon et al. 2006
Predictive value of culture detection and identification.most isolates of Candida species obtained from blood cultures are clinically significant. Leon, 2006; Bouza 2005; Pittet 1994; Eggimann 2003
Predictive value of culture detection and identification.most isolates of Candida species obtained from blood cultures are clinically significant..others such as Aspergillus species are not. Respiratory tract specimens might be problematic, hence have high diagnostic value in immunocompromised patients. Meersemann 2007, 2005
Value of BAL and molds (culture/microscopic, LKI 1994-2007) Hematology Sensitivity (40%/56%) PPV (80%/100%) ICU Sensitivity (71%/96%) PPV (76%/78%) Organ transplant Sensitivity (77%/97%) PPV (80%/96%) unpublished data, Lass-Flörl
Invasive fungal infection
Genus, species.?
Genus and Species Distribution-what are the concerns? C. glabrata: panazole resistant C. parapsilosis: MIC echinocandins Aspergillus spp: (pan) azole resistant A. terreus: AMPHO B resistant Zygomyzetes: susceptible to POS and AMPHO B Scedosporium prolificans: multidrug resistant Fusarium solani: multidrug resistant Richardson & Lass-Flörl 2008
Yeasts (blood cultures) Non-neutropenic Neutropenic Severe sepsisseptic shock No azole prophylaxis Azole prophylaxis Candine Polyene Candine Fluconazole: C.parapsilosis Candine: C. glabrata Candine Polyene ICAAC 2007 (IDSA Guidelines for Candida 2008)
The identification of the genus/species guides the physician in the choice of antifungal therapy. Species identifcation must be done in yeasts obtained from sterile body sites. Genus identifcation must be done in molds obtained from sterile body sites. Species identification should be done in molds isolated from immunosuppressed patients. Aspergillus (fumigatus, flavus, terreus, ). Candida (albicans, krusei, glabrata ). Zygomyzeten (Mucor sp., Rhizopus sp, ).
Susceptibility Testing 90-60 rule
MICs have value (non-c.albicans; non-aspergillus fumigatus; non responder; long term treatment) but knowledge of species is almost as good! Balajee 2007
Cross-"resistance" to azoles in C. glabrata blood isolates (n=149) 0.12 1 VRZ (µg/ml) 0.03 0.06 0.12 0.25 0.5 1 2 4 8 FCZ (µg/ml) 1 1 1 4 1 4 6 1 8 2 15 21 16 2 16 1 1 8 20 2 32 1 1 8 64 1 3 2 2 3 14 1 10 Lortholary et al. AAC 2007
Take home message... Blutkulturen sind das diagnostische Werkzeug zur Abklärung einer IC Andere steril gewonnene Materialien Candida spezies aus unsterilen Materalien=Kolonisation und keine Infektion Resistenztestungen für Non C.albicans und Azole Kreuzresistenzen unter Azolen vorhanden:lokale Epidemiologie
Ausblick 2009
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