Cryptococcal pneumonia and meningitis

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

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
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 - routine,
fungal and TB culture - Viral culture and
PCR for HSV and CMV - cells, protein and
glucose - TB PCR - Aspergillus antigen
/ PCR Chest Xray

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 1979301126
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 Med1990113182
23
Open study of cryptococcal meningitis in AIDS
with itraconazole

• 37 pts received either
• 1) ITZ 400mg/d (n 25)
• or 2) AmB lt7d, then ITZ (n12)
• CR () PR () Fail / UE ()
• ITZ alone 40 24 36
• AmB then ITZ 83 8 8

Denning et al, Mycoses in AIDS 1990305.
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
• p0.06

van der Horst et al, NEJM 199733115
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 199733115
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 199928291
27
Meningitis in subsarahan AfricaCape Town3
years sequential LPs
Jarvis et al, BMC Infect Dis 20101067
28
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)
Cryptococcal meningitis Rx
P lt0.001
Nussbaum et al, Clin Infect Dis 201050338
29
Cryptococcal meningitis Rx
Nussbaum et al, Clin Infect Dis 201050338
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 gt800mg/d flucytosine (100 mg/kg/d)

Perfect et al, IDSA Guidelines. Clin Infect Dis
201050291
31
Management of cryptococcal meningitis
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 gt250, repeat LP in 2 days and drain
CSF IF CSF pressure gt250 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 gt6m, or, in non-AIDS CSF antigen
lt18after at least 6m Rx

32
Coccidioidal meningitis
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

33
Aspergillus meningitis
gt40 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

WWW.aspergillus.org.uk