Fungal Infections: Management and Management and

Reporting

Marcie Tomblyn, MD, MSy , ,Associate Member, Moffitt Cancer Center

February 25, 2010February 25, 2010

ObjectivesObjectives

Review common fungal infections in HCT patientsReview current available therapiesDiscuss clinical examples with reporting issues

OrganismsOrganisms

Yeasts

M ldMoldsRequire the fungal infection form infection form supplement

MoldsMolds

Mucormycosis AspergillusMucormycosis Aspergillus

Definitions of Fungal InfectionDefinitions of Fungal Infection

ProvenOrganism seen on pathology with associated tissue damageOrganism identified by culture from a sterile procedure from a sterile area with associated clinical/radiologic findings of infection

ProbableRequires 1 host factor + 1 clinical factor + 1 microbiologic factor

PossibleRequires 1 host factor + 1 clinical factorNo microbiologic factor needed

EORTC/MSG Consensus

Host FactorsHost Factors

Recent neutropenia for >10 days Recent neutropenia for >10 days associated with the onset of fungal diseaseReceipt of allogeneic transplantSteroid use of >0.3mg/kg/day for >3 wksTreatment with T-cell immune suppressive meds in prior 90 days

i e Cyclosporine CAMPATH Fludarabinei.e. Cyclosporine, CAMPATH, FludarabineInherited severe immune deficiency

EORTC/MSG Consensus

Clinical FactorsClinical FactorsLower Resp Tract Sinonasal Infection

I i ith i iti CT findings of well-defined nodule, wedge shaped infiltrate, air-crescent or cavity OR

Imaging with sinusitis plus either acute localized pain, nasal ulcer or black eschar, or crescent, or cavity, OR

Nonspecific nodule(s) with pleural rub, pleural pain, or hemoptysis

,extension beyond bony borders

CNSp , p y

TracheobronchitisUlceration nodule

Focal CNS lesionsMeningeal enhancement

Disseminated Ulceration, nodule, pseudomembrane, eschar, or plaque seen on bronch

Disseminated candidiasis

Target lesions in liver and/or spleenand/or spleen

EORTC/MSG Consensus

Microbiologic FactorsMicrobiologic FactorsCytology, Direct Mi C lt

Detection of Antigen, ll ll l i Microscopy, or Culture

Sputum, BAL, or bronchial brush findings with fungal elements by

cell wall, or nucleic acids

Galactomannan: single iti i with fungal elements by

culture or direct observationSinus aspirate with

positive in serum, plasma, pleural fluid, BAL, or CSFBeta-D-glucan: single Sinus aspirate with

findings of fungal elements by culture or direct observation

Beta-D-glucan: single serum sample positivePCR for nucleic acids are NOT considered

Skin ulcerations require both culture and direct observation of fungal elementselements

EORTC/MSG Consensus

Prophylaxis vs TreatmentProphylaxis vs Treatment

Prophylaxis: started about the time of Prophylaxis: started about the time of conditioning to PREVENT infections

Example: Initiation of micafungin at the start f di i i f ll i lof conditioning for allogeneic transplant

Treatment: drugs used for Treatment: drugs used for MANAGEMENT of the infection

Example: Increase of dose of micafungin to p ghigher doses due to clinical findings—likely will add another antifungal as well

Infection Prophylaxis

Fungal Infection TreatmentFungal Infection Treatment

Will have the same drug choicesDoses may be increased to “treatment” dosesdoses

Example: Vori 200mg BID = prophylaxis Vori 200mg BID = prophylaxis Vori 300mg BID = treatment

May have additional antifungal therapiesMay have additional antifungal therapiesDouble therapyTriple therapyTriple therapy

Reporting of Fungal InfectionsReporting of Fungal Infections

Forms for reportingPre-transplant infections

Form 2000Form 2046 (supplement)

Post-transplant infectionsForm 2100F 2146 ( l t)Form 2146 (supplement)Form 2200

Reporting Infectionsp g

What is the same infection? (i e don’t report again)(i.e. don t report again)

Bacteria Virus Fungal

≤7 days• All bacteria (except Clostridium

≤14 days• VZV • HZV

≤14 days• Yeasts

Candida(except Clostridium Difficile)

≤30 days

• HZV• Adenovirus• Enterovirus

CandidaCryptococcus

≤30 days• Clostridium Difficile

• Influenza virus• Parainfluenza• Rhinovirus

≤90 days• Molds

Aspergillus

≤ 365 days•Helicobacter pylori

≤60 days• CMV • HSV

p gFusariumMucor

• HSV• Polyomavirus

Fungal Insert g(Forms 2046, 2146)

To obtain more specific information To obtain more specific information about mold infections

Requests detailed information of DiagnosisDiagnosisProphylaxisThTherapy

Mold Infections of Interest

AspergillusFusariumFusariumMucormycosisRhizopusRhizopusZygomycetes

Key Data ElementsKey Data Elements

Date of infectionSite of infectionDiagnostic testTreatment

F l d t th ti f Fungal drugs at the time of diagnosisTherapy up to 6 months after Therapy up to 6 months after diagnosis

Mold infection Mold infection

Sites of InfectionSites 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 morenon-contiguous sites

Mold Diagnostic Test gOptions

BiopsyCultureCytologyKOH/Calcofluor stainAspergillus galactomannanUnknown

Therapy Data CollectionTherapy Data Collection

*If treatment held for less than 7 consecutive days and then restarted, do not consider as “Therapy Stopped”

Clinical ScenariosClinical Scenarios