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CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS

CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS. Stephen J. Gluckman, M.D. Botswana-UPENN Partnership. Microbiology. Encapsulated yeast 4 serotypes A ( C. neoformans v grubii ) B and C ( C. gatti ) D ( C. neoformans v neoformans ) All types can cause human disease Life cycle

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CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS

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  1. CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS Stephen J. Gluckman, M.D. Botswana-UPENN Partnership

  2. Microbiology • Encapsulated yeast • 4 serotypes • A (C. neoformans v grubii) • B and C ( C. gatti) • D (C. neoformans v neoformans) • All types can cause human disease • Life cycle • Asexual: yeast that reproduce by budding • Human infections • Sexual: only seen in the laboratory

  3. Ecology and Epidemiology • World wide • C. neoformans associated with bird droppings • C. gatti not associated with birds, associated with eucalyptus trees • Generally an infection of immunocompromised but can cause clinical disease in healthy persons • Decreased Cell-mediated immunity • AIDS – CD 4 usually < 100 • Prolonged corticosteroids • Organ transplant

  4. Ecology and Epidemiology • 15-30% of AIDS patients in Sub-Saharan Africa* • Much less common in children • No person to person transmission *Powderly, WG Clin Infect Dis 1993

  5. Clinical Presentations • Pulmonary • Asymptomatic nodule • Symptomatic: not distinguishable from other causes • History, PE, routine laboratory testing does not produce features peculiarly suggestive of cryptococcal infection • Diagnosis • Staining of biopsy specimen • Culture of sputum and/or blood • Serum cryptococcal antigen (CRAG) • All patients with pulmonary disease need a CSF examination to r/o sub clinical meningitis

  6. Silver Stain

  7. Clinical Presentations • Cutaneous • Disseminated disease • Looks similar to molluscum contageosum • Diagnosis: • Unroofing a lesion and making a smear and culture • Serum CRAG • All patients with cutaneous disease need a CSF examination to r/o sub clinical meningitis

  8. Clinical Presentations • Cryptococcal Meningitis • Typical • Subacute onset of fever and headache • Photophobia and/or meningeal signs in only 25% • Less typical • Seizures • Confusion • Progressive dementia • Visual or hearing impairment • FUO • Diagnosis • CSF • Serum CRAG: > 99% sensitive in AIDS patients

  9. Cryptococcal Meningitis • In 2003 there were 193 (+) CSF cultures for cryptococcus from PMH * • Leucocytes • No leucocytes in 31% • Only 1-10 leucocytes in 23% • 7% had > 250 leucocytes • 30% of these had predominately PMN’s • 95% (+) India Ink • 1% (-) cryptococcal antigen • Literature • Sensitivity: 93-100% • Specificity: 93-98 % *Bisson et al

  10. India Ink

  11. Prognosis for Cryptococcal Meningitis • Prior to 1950 it was uniformly fatal • Amphotericin B introduced and mortality fell to the 30-40% range • In 1970’s 5-FC was released • Not for monotherapy • Decreased relapse rate when used with Amphotericin B • Mortality with current regimens: 10% • Predictors of death • Altered mental status • CSF CRAG > 1024 • CSF cell count < 20 • Changes in serum CRAG titer do not correlate with clinical outcome. So no need to follow

  12. Summary of Diagnostic Options • Culture • White mucoid colonies within 48hours • Blood cultures often (+) in immunosuppressed patients • 2/3rds with meningitis • Tissue • Silver or mucicarmine stain • India Ink for CSF • Cryptococcal antigen • Serum and CSF are 99% sensitive in AIDS patients • Serum is less sensitive in normal hosts

  13. Cryptococcal MeningitisTreatment • Antifungal agents • Induction • Consolidation • Maintenance • Pressure management

  14. Treatment**Modified IDSA Guidelines • Immunosuppressed (pulmonary, cutaneous, or meningitis) • Induction • Amphotericin B 0.7-1 mg/kg/day plus 5-flucytosine 100mg/kg/day x 2 weeks then • Consolidation • Fluconazole 400 mg/day x 6-10 weeks then • Suppression • Fluconazole 200 mg/day x ?

  15. Cryptococcal MeningitisTreatmentOne More Thing • Anti-fungal: induction, consolidation, maintenance • Pressure management • Elevated pressure • 75% > 200 • 25% > 350 • Repeated lumbar punctures • Increased pressure: daily until normal x several days • Normal pressure: recheck at 2 weeks prior to switching to fluconazole • Lumbar drain • VP shunt: if still elevated at 1 month • No role for • acetazolamide, mannitol • Steroids: ?

  16. Treatment • Other options • Fluconazole induction • Increased mortality • Not IDSA first choice • 5 FC monotherapy • Not an option because of resistance • 5-FC plus Fluconazole • Increased long term toxicity but an option • Caspofungin • No efficacy • Voriconazole • Good in vitro activity but little clinical experience

  17. Summary • Cryptococcal infections are common in patients with AIDS • In patients with AIDS cryptococcal infections are seen in patients with the lowest CD 4 (+) cell counts • Prolonged therapy and secondary prophylaxis is necessary • For meningitis both anti-fungal therapy and aggressive pressure management are required

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