Fungal Infections: Management and Reporting Marcie Tomblyn, MD, MS Associate Member, Moffitt Cancer Center February 25, 2010
Objectives Review common fungal infections in HCT patients Review current available therapies Discuss clinical examples with reporting issues
Organisms Yeasts Molds Require the fungal infection form supplement
Molds Mucormycosis Aspergillus
Definitions of Fungal Infection Proven Organism seen on pathology with associated tissue damage Organism identified by culture from a sterile procedure from a sterile area with associated clinical/radiologic findings of infection Probable Requires 1 host factor + 1 clinical factor + 1 microbiologic factor Possible Requires 1 host factor + 1 clinical factor No microbiologic factor needed EORTC/MSG Consensus
Host Factors Recent neutropenia for >10 days associated with the onset of fungal disease Receipt of allogeneic transplant Steroid use of >0.3mg/kg/day for >3 wks Treatment with T-cell immune suppressive meds in prior 90 days i.e. Cyclosporine, CAMPATH, Fludarabine Inherited severe immune deficiency EORTC/MSG Consensus
Lower Resp Tract Clinical Factors CT findings of welldefined nodule, wedge shaped infiltrate, air- crescent, or cavity, OR Nonspecific nodule(s) with pleural rub, pleural pain, or hemoptysis Tracheobronchitis Ulceration, nodule, pseudomembrane, eschar, or plaque seen on bronch Sinonasal Infection Imaging with sinusitis iti plus either acute localized pain, nasal ulcer or black eschar, or extension beyond bony borders CNS Focal CNS lesions Meningeal enhancement Disseminated candidiasis Target lesions in liver and/or spleen EORTC/MSG Consensus
Microbiologic Factors Cytology, Direct Microscopy, or Culture Sputum, BAL, or bronchial brush findings with fungal elements by culture or direct observation Sinus aspirate with findings of fungal elements by culture or direct observation Skin ulcerations require both culture and direct observation of fungal elements Detection of Antigen, cell wall, or nucleic acids Galactomannan: single positive in serum, plasma, pleural fluid, BAL, or CSF Beta-D-glucan: single serum sample positive PCR for nucleic acids are NOT considered EORTC/MSG Consensus
Prophylaxis vs Treatment Prophylaxis: started about the time of conditioning to PREVENT infections Example: Initiation of micafungin at the start of conditioning i i for allogeneic transplant Treatment: drugs used for MANAGEMENT of the infection Example: Increase of dose of micafungin to higher doses due to clinical findings likely will add another antifungal as well
Infection Prophylaxis
Fungal Infection Treatment Will have the same drug choices Doses may be increased to treatment doses Example: Vori 200mg BID = prophylaxis Vori 300mg BID = treatment May have additional antifungal therapies Double therapy Triple therapy
Reporting of Fungal Infections Forms for reporting Pre-transplant infections Form 2000 Form 2046 (supplement) Post-transplant infections Form 2100 Form 2146 (supplement) Form 2200
Reporting Infections
What is the same infection? (i.e. don t report again) Bacteria Virus Fungal 7 days All bacteria (except Clostridium Difficile) 30 days Clostridium Difficile 365 days Helicobacter pylori 14 days VZV HZV Adenovirus Enterovirus Influenza virus Parainfluenza Rhinovirus 60 days CMV HSV Polyomavirus 14 days Yeasts Candida Cryptococcus 90 days Molds Aspergillus Fusarium Mucor
Fungal Insert (Forms 2046, 2146) To obtain more specific information about mold infections Requests detailed information of Diagnosis Prophylaxis Therapy
Mold Infections of Interest Aspergillus Fusarium Mucormycosis Rhizopus Zygomycetes
Key Data Elements Date of infection Site of infection Diagnostic test Treatment Fungal drugs at the time of diagnosis Therapy up to 6 months after diagnosis
Mold infection
Sites of Infection **Di i t d i f ti t h th i id tifi d t 3 **Disseminated infections must have the organism identified at 3 or more non-contiguous sites
Biopsy Culture Mold Diagnostic Test Options Cytology KOH/Calcofluor stain Aspergillus galactomannan Unknown
Therapy Data Collection *If treatment held for less than 7 consecutive days and then restarted, do not consider as Therapy Stopped
Clinical Scenarios