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Cryptococcal pneumonia and meningitis

Cryptococcal pneumonia and meningitis. Cryptococcus neoformans. Cryptococcus gattii or grubii - serotype B or C. Pulmonary cryptococcosis - large nodule. SP age 69 years. Pulmonary cryptococcosis - cavitating nodule. Pulmonary cryptococcosis - cavitating nodule.

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Cryptococcal pneumonia and meningitis

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  1. Cryptococcal pneumonia and meningitis

  2. Cryptococcus neoformans

  3. Cryptococcus gattii or grubii - serotype B or C

  4. Pulmonary cryptococcosis • - large nodule

  5. SP age 69 years

  6. Pulmonary cryptococcosis • - cavitating nodule

  7. Pulmonary cryptococcosis • - cavitating nodule

  8. Pulmonary cryptococcosis • - cavitating pneumonia

  9. Pulmonary cryptococcosis • - consolidation

  10. Pulmonary cryptococcosis • - bilateral atelectasis

  11. Pulmonary cryptococcosis • - ‘atypical pneumonia’

  12. Pulmonary cryptococcosis • - cavitating pneumonia

  13. Pulmonary cryptococcosis -IDSA guidelines

  14. Pulmonary cryptococcosis -IDSA guidelines

  15. SP age 69 years – lung biopsy (PAS)

  16. Subacute presentation - 1-4 weeks Headache, confusion / reduced acuity, vomiting common Focal signs, hydrocephalus and extrameningeal features, occasional Neck stiffness uncommon in immunocompromised Differential diagnosis is wide, including non-infectious causes Clinical features of TBM and fungal meningitis

  17. Investigations - immunocompromised patient TB and fungal blood culture MR scan of brain (better than CT) CSF with opening pressure CSF analysis - microscopy for TB and yeast cells (India Ink), and bacteria

  18. India ink for cryptococcal meningitis

  19. TB and fungal blood culture MR scan of brain (better than CT) CSF with opening pressure CSF analysis - microscopy for TB and yeast cells (India Ink), and bacteria - routine, fungal and TB culture - Viral culture and PCR for HSV and CMV - cells, protein and glucose - TB PCR - Aspergillus antigen / PCR Chest Xray Investigations - immunocompromised patient

  20. Cryptococcal meningitis in AIDS, a disseminated disease

  21. First randomised study of cryptococcal meningitis 51 pts received either 1) AmB 0.4mg/kg/d for 10 wks or 2) AmB 0.3mg/kg/d + 5FC for 6 wks Resp (%) Relapse (%) Died (%) AmB 10 wks 41 18 47 AmB +5FC 6 wks 67 4 24 Bennett et al, NEJM 1979;301:126

  22. Randomised study of cryptococcal meningitis in AIDS 21 pts received either 1) Flu 400mg/d for 10 wks or 2) AmB 0.7mg/kg/d + 5FC for 10 wks Resp (%) Died (%) Pos CSF (d) Flu 42 28 41 AmB +5FC 100 0 16 Larsen et al, Am J Med1990;113:182

  23. Open study of cryptococcal meningitis in AIDS with itraconazole 37 pts received either 1) ITZ 400mg/d (n = 25) or 2) AmB <7d, then ITZ (n=12) CR (%) PR (%) Fail / UE (%) ITZ alone 40 24 36 AmB then ITZ 83 8 8 Denning et al, Mycoses in AIDS 1990;305.

  24. Randomised study of cryptococcal meningitis in AIDS 381 pts received either 1) AmB 0.7mg/d for 2 wks or 2) AmB 0.7mg/kg/d + 5FC 2 wks, then re-randomised to ITZ or FLU 400mg/d for 8 weeks Resp (%) Died (%) Pos CSF (%) AmB 83 5 40 AmB + 5FC 78 6 49* * p=0.06 van der Horst et al, NEJM 1997;331:15

  25. Randomised study of cryptococcal meningitis in AIDS 306 pts received either 1) FLU 400mg/d for 8 wks or 2) ITZ 400mg/d for 8 wks Resp (%) Died (%) Pos CSF (%) Flu 68 1 3 ITZ 70 3 5 van der Horst et al, NEJM 1997;331:15

  26. Randomised study of maintenance of cryptococcal meningitis in AIDS Cox proportional hazards model Risk of relapse p value RR (95% CI) ITZ Rx 0.06 4.32 (0.9,19.8) No prior 5FC 0.04 5.88 (1.3, 27.1)  serum CRAG 0.08 1.2 (1, 1.38) Saag et al, Clin Infect Dis 1999;28:291

  27. Meningitis in subsarahan AfricaCape Town3 years sequential LPs Jarvis et al, BMC Infect Dis 2010;10:67

  28. Cryptococcal meningitis Rx HIV-seropositive, antiretroviral-naive patients experiencingtheir first episode of cryptococcal meningitis were randomized to receive 14 days of - fluconazole (1200 mg/d) alone (A) or - fluconazole (1200 mg/d) alone + flucytosine (100 mg/kg/d) (B) followed by fluconazole (800 mg/d) P <0.001 Nussbaum et al, Clin Infect Dis 2010;50:338

  29. Cryptococcal meningitis Rx Nussbaum et al, Clin Infect Dis 2010;50:338

  30. Choice of initial antifungal therapy for cryptococcal meningitis • Priority sequence • Amphotericin B (0.7- 1.0 mg/Kg/d) • or AmBisome 3-4mg/Kg/d) • + flucytosine (100 mg/kg/d) • Fluconazole >800mg/d + flucytosine (100 mg/kg/d) Perfect et al, IDSA Guidelines. Clin Infect Dis 2010;50:291

  31. LP essential, CT / MR scan desirable, but not essential Initiate Rx - Amphotericin B 0.7mg/kg/d or Liposomal amphotericin B 4mg/kg/d + Flucytosine 25mg/kg/dose tid If CSF pressure >250, repeat LP in 2 days and drain CSF IF CSF pressure >250 for several days use acetazolamide, (not steroids) and consider lumbar shunt If patient responding, switch to fluconazole 400mg/d. Stop therapy if HARRT Rx successful for >6m, or, in non-AIDS CSF antigen <1:8after at least 6m Rx Management of cryptococcal meningitis

  32. Pointers Travel history Extra-meningeal disease No suggestions of TB Lack of response to TB treatment Essential tests CSF coccidioidal antibody Treatment High dose azole or intrathecal amphotericin B Lifelong Coccidioidal meningitis

  33. >40 cases reported Pointers Neutrophil predominant CSF Immunocompromised, neurosurgery / IT antibiotics, IVDA, or extension from Aspergillus sinusitis Essential tests CSF Aspergillus antigen (galactomannan) Aspergillus PCR, fungal culture Treatment IV itraconazole or voriconazole or amphotericin B No steroids Outcome reasonable, if diagnosis made Aspergillus meningitis WWW.aspergillus.org.uk

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