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    Opportunistic Mycoses Opportunistic Mycoses Presentation Transcript

    • Opportunistic Mycoses
      • Infections due to fungi of low virulence in patients who are immunologically compromised
      www.freelivedoctor.com
    • Medical Mycology Iceberg www.freelivedoctor.com
    • PATHOGENIC FUNGI
      • NORMAL HOST
        • Systemic pathogens - 25 species
        • Cutaneous pathogens - 33 species
        • Subcutaneous pathogens - 10 species
      • IMMUNOCOMPROMISED HOST
          • Opportunistic fungi - 300 species
      www.freelivedoctor.com
    • HOST-PATHOGEN EQUILIBRIUM
      • NUMBER OF ORGANISMS X VIRULENCE = DISEASE HOST RESISTANCE
      www.freelivedoctor.com
    • Opportunistic Fungi
      • 1. Saprophytic - from the environment
      • 2. Endogenous – a commensal organism
      www.freelivedoctor.com
    • Opportunistic Fungi
      • Include many species from:
      • A (Aspergillus)
      • To
      • Z (Zygomyces)
      www.freelivedoctor.com
    • MOST SERIOUS OPPORTUNISTIC INFECTIONS
      • CANDIDA SPECIES
      • ASPERGILLUS SPECIES
      • MUCOR SPECIES (ZYGOMYCES)
      www.freelivedoctor.com
    • Upward Trend In Opportunistic Mycoses
      • Increased clinical awareness
      • Improved clinical diagnostic tools
      • Improved laboratory diagnostic technics
      • An increase in susceptible hosts.
      • More invasive diagnostic and therapeutic procedures
      www.freelivedoctor.com
    • Must distinguish between
      • Transient fungemia
      • Colonization
      • Infection
      www.freelivedoctor.com
    • Transient fungemia
      • The fortuitous isolation of a commensal or environmental organism
      www.freelivedoctor.com
    • COLONIZATION EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT Multiplication of an organism at a given site without harm to the host www.freelivedoctor.com
    • INFECTION EYE SKIN UROGENITAL TRACT ANUS MOUTH RESPIRATORY TRACT Invasion and multiplication of organisms in body tissue resulting in local cellular injury . www.freelivedoctor.com
    • Predisposing Factors
      • Malignancies
      • Leukemias
      • Lymphomas
      • Hodgkins Disease
      www.freelivedoctor.com
    • Predisposing Factors
      • Drug therapies
      • Anti-neoplastics
      • Steroids
      • Immunosuppressive drugs
      www.freelivedoctor.com
    • Predisposing Factors
      • Antibiotics
      • Over-use or inappropriate use of antibiotics alter the normal flora allowing fungal overgrowth
      www.freelivedoctor.com
    • Predisposing Factors
      • Therapeutic procedures
      • Solid organ or bone marrow transplant
      • Open heart surgery
      • Indwelling catheters
      • Artificial heart valves
      • Radiation therapy
      www.freelivedoctor.com
    • Predisposing Factors
      • Other Factors
      • Severe burns
      • Diabetes
      • Tuberculosis
      • IV Drug use
      www.freelivedoctor.com
    • Predisposing Factors
      • AIDS
      www.freelivedoctor.com
    • Human Immunodeficiency Virus (HIV) HIV destroys the CD4 helper T cells www.freelivedoctor.com
    • CD4 helper T cells are the basis of cell mediated immunity and play a role in host defenses against fungal diseases ERGO www.freelivedoctor.com
      • Virtually all AIDS patients will have a fungal infection sometime during the course of their illness
      www.freelivedoctor.com
    • BIOFILMS
      • A POLYSACCHARIDE SLIME WHICH IS A MICROCOLONY OF ORGANISMS CONTAINING CHANNELS TO BRING IN NUTRIENTS AND CARRY OFF WASTE
      www.freelivedoctor.com
    • Diagnosis of opportunistic infections requires a high index of suspicion
      • Atypical signs or symptoms
      • Unusual organ affinity
      • Outside the endemic area
      • Unusual Histopathology
      • Etiologic agent may be a saprophyte
      www.freelivedoctor.com
    • CLINICAL PRESENTATION
      • Atypical Signs and Symptoms
      • Unusual Organ Affinity
      • Outside Endemic Area
      • Unusual histopathology
      • Unusual Pathogens
      www.freelivedoctor.com
    • NORMAL PATIENT
      • Malasezzia furfur
      • Tinea versicolor
      • (mild disease)
      www.freelivedoctor.com
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    • COMPROMISED PATIENTS
      • Malasezzia furfur can cause disseminated infection--------Particularly in patients receiving hyperalimentation.
      www.freelivedoctor.com
    • COMPROMISED IMMUNE SYSTEM Malasezzia furfur NUMBER OF ORGANISMS x LOW VIRULENCE = DISEASE HOST RESISTANCE www.freelivedoctor.com
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    • CLINICAL PRESENTATION
      • Atypical Signs and Symptoms
      • Unusual Organ Affinity
      • Outside Endemic Area
      • Unusual histopathology
      • Unusual Pathogens
      www.freelivedoctor.com
    • Candida species Endogenous www.freelivedoctor.com
    • Normal Flora
      • The population of microorganisms that may be found residing in or on the human body without causing disease.
      www.freelivedoctor.com
    • COMPETENT IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS x VIRULENCE = NO DISEASE HOST RESISTANCE www.freelivedoctor.com
    • COMPROMISED IMMUNE SYSTEM Candida albicans NUMBER OF ORGANISMS = DISEASE HOST RESISTANCE www.freelivedoctor.com
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    • IMMUNOCOMPROMISED PATIENTS CAN DEVELOP HEPATIC CANDIDIASIS www.freelivedoctor.com
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    • Candida species
      • In the previous lecture I only mentioned Candida albicans . There are several Candida species that infect the compromised host.
      www.freelivedoctor.com
    • Candida species
      • C. glabrata
      • C. krusei
      • C. torulopsis
      • C. parapsilosis
      • C. lusitaniae
      • C. dubliniensis
      www.freelivedoctor.com
    • Cryptococcosis
      • A sub-acute or chronic infection which may affect the lungs or skin but most commonly manifests as a meningitis
      www.freelivedoctor.com
    • Ecological Niche Cryptococcus neoformans
      • pigeon droppings
      • Chicken droppings
      www.freelivedoctor.com
    • Cryptococcus neoformans PORTAL OF ENTRY
      • INHALATION
      • INOCULATION
      www.freelivedoctor.com
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    • Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = NO DISEASE NORMAL HOST www.freelivedoctor.com
    • Cryptococcus neoformans LOW NUMBER X HIGH VIRULENCE = INFECTION COMPROMISED HOST www.freelivedoctor.com
    • Cryptococcosis
      • In the Compromised patient:
      • Amphotericin B
      • 5 FC
      • Then Fluconazole the remainder of their life.
      • Fluconazole penetrates the CSF
      www.freelivedoctor.com
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    • SPOROTRICHOSIS Primarily a disease of the cutaneous tissue and lymph nodes. Recently, pulmonary disease. www.freelivedoctor.com
    • PORTALS OF ENTRY
      • Inhalation
      • Inoculation
      www.freelivedoctor.com
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    • ECOLOGICAL ASSOCIATIONS
      • Rose thorns
      • Sphagnum moss
      • Timbers
      • Soil
      www.freelivedoctor.com
    • SPOROTRICHOSIS www.freelivedoctor.com
    • www.freelivedoctor.com
    • Blastomycosis in AIDS patients
      • One report
      • 16 Patients
      • 10 localized disease
        • 7-lung, 2-skin, 1 CNS
      • 6 Disseminated
        • 5/6 – CNS
      • All did poorly
      www.freelivedoctor.com
    • Aspergillus species HIGH NUMBER X LOW VIRULENCE = NO DISEASE NORMAL HOST www.freelivedoctor.com
    • Aspergillus species LOW NUMBER X LOW VIRULENCE = INFECTION COMPROMISED HOST www.freelivedoctor.com
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    • CLINICAL PRESENTATION
      • Atypical Signs and Symptoms
      • Unusual Organ Affinity
      • Outside Endemic Area
      • Unusual histopathology
      • Unusual Pathogens
      www.freelivedoctor.com
    • AIDS Patient
      • Pneumocystis pneumonia
      • Disseminated coccidioidomycosis
      • (not pulmonary)
      • Mycelial forms in abscesses
      • (not spherules)
      • Outside the endemic area
      • (St. Louis, MO)
      www.freelivedoctor.com
    • Spherules www.freelivedoctor.com
    • www.freelivedoctor.com
    • HISTOPLASMOSIS IN AIDS PATIENTS
      • ALL CASES ARE DISSEMINATED
      • RELAPSES ARE GREATER THAN 50 %
      • RAPIDLY FATAL IN 10 %
      www.freelivedoctor.com
    • AIDS Patients
      • Disseminated histoplasmosis
      • (not pulmonary disease)
      • New York City
      • (outside the endemic region)
      www.freelivedoctor.com
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    • CLINICAL PRESENTATION
      • Atypical Signs and Symptoms
      • Unusual Organ Affinity
      • Outside Endemic Area
      • Unusual Histopathology
      • Unusual Pathogens
      www.freelivedoctor.com
    • INFLAMMATORY REACTION
      • NORMAL HOST
        • PYOGENIC
        • GRANULOMATOUS
      • IMMUNODEFICIENT HOST
        • NECROTIC
      www.freelivedoctor.com
    • CLINICAL PRESENTATION
      • Atypical Signs and Symptoms
      • Unusual Organ Affinity
      • Outside Endemic Area
      • Unusual histopathology
      • Unusual Pathogens
      www.freelivedoctor.com
    • Opportunistic Fungi
      • Include many species from:
      • A (Aspergillus)
      • To
      • Z (Zygomyces)
      www.freelivedoctor.com
    • Penicillium marneffei
      • Usually not a pathogen
      • The only dimorphic penicillium
      • Produces a red pigment
      • Endemic in the Far East
      www.freelivedoctor.com
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    • Pneumocystis jiroveci Recently confirmed as a member of Kingdom Fungi. Formerly thought to be a protozoan. www.freelivedoctor.com
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    • Cryptococcus neoformans
      • Diabetes mellitus
      • Tuberculosis
      • Lymphoma
      • Hodgkin’s disease
      • Corticosteroid therapy
      • Immunosuppression
      www.freelivedoctor.com
    • Candida albicans
      • Prolonged antibiotic therapy
      • Prolonged intravenous therapy
      • Prolonged urinary catheters
      • Corticosteroid therapy
      • Diabetes mellitus
      • Hyperalimentation
      • Immunosuppression
      www.freelivedoctor.com
    • Torulopsis (Candida) glabrata
      • Cytotoxic drugs
      • Immunosuppression
      • Diabetes mellitus
      • Hyperalimentation
      • Intravenous catheters
      www.freelivedoctor.com
    • www.freelivedoctor.com
    • Mucormycetes
      • Diabetes mellitus
      • Leukemias
      • Corticosteroid therapy
      • Intravenous therapy
      • Severe burns
      www.freelivedoctor.com
    • Aspergillus species
      • Leukemias
      • Corticosteroid therapy
      • Tuberculosis
      • Immunosuppression
      • Intravenous drug abuse
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • New Drugs
      • New therapeutic regimen
      • Aggressive therapy
      • Conjunctive therapy
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • New Drugs
      • Lipid Amphotericin B
      • Third generation azoles
      • (Posaconazole, Voriconazole)
      • New classes of antifungal agents
      • (Echinocandins)
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • New Therapeutic Regimen
      • Combination Therapy
      • Simultaneously administering two drugs
      • Sequential Tx with two or more drugs
      • Alternate Administration of two or more
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • AGGRESSIVE THERAPY
      • FOR IMMUNOCOMPROMISED PATIENTS
      • Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy.
      • Posaconazole now approved.
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • AGGRESSIVE THERAPY
      • FOR IMMUNOCOMPROMISED PATIENTS
      • 2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials.
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • AGGRESSIVE THERAPY
      • FOR IMMUNOCOMPROMISED PATIENTS
      • 3. Pre-emptive – When there is some additional evidence of fungal infection (serology, isolate, etc.)
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • CONJUNJUNCTIVE THERAPY
      • Antifungal agent plus a recombinant monoclonal antibody.
      www.freelivedoctor.com
    • IMPROVING TREATMENT
      • CONJUNJUNCTIVE THERAPY
      • FOR IMMUNOCOMPROMISED PATIENTS
      • The use of anti-fungal agents with immunotherapy.
      www.freelivedoctor.com
    • Immunotherapy
      • Interferons
      • Colony stimulating factors
      • Interleukins
      www.freelivedoctor.com