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Riyadh Microbiology/Infectious Disease
Club Meeting
“Cancer Analogy”
Hail M. Al-Abdely, MD
Section of Infectious Diseases
Department of Medicine
King Faisal Specialist Hospital & Research Centre
History

2 Nov 1999

13 y/o Male previously healthy referred from
Dahran Health Center with a 3-months h/o
generalized weakness & wt loss. RUQ pain.

CT abd revealed multiple hepatic lesions and
mediastinal lymphadenopathy
Course at KFSH
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Chronically ill. No fever
Hepatomegaly
WBC 8.25 with 35% eosinophils
Fundoscopy:

Multiple retinal lesions
Possible Diagnoses??
FNA from the liver showed fungal hyphae
 Culture was negative
 Treated with ABLC and itraconazole for 4 weeks
with no response

Course

FNA from liver
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Mediastinal lymph node bx
What Fungus?
Cladophialophora bantiana
Course

Therapy
Liposomal AmB 7.5mg/kg/day (Stopped 7 May
2000)
 Itraconazole 200mg Q12hrs


Improved clinically and radiologically
15 Jan 2000
1 July 2000
29 Dec 2001
Course
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30 June 2002
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C/O nausea and vomiting and coordination
impairment
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Irregular on itraconazole for 2 months
2 July 2002
8 July 2002
8 July 2002
Course
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Treated with i.v itraconazole 250mg Q12 hrs

Discharged (30 July 2002) on liquid itraconazole
300 mg BID

Improved
Course

27 Aug 02
Nausea , vomiting, bilateral weakness and
discoordination
 MRI brain worse but CT chest better
 Therapy

i.v itraconazole
 i.v 5-FC
 i.v liposomal AmB

28 Sep 2002
What to do?
Course

Voriconazole 200mg i.v Q12 hrs for 3 weeks
followed by po.
Remarkable improvement and discharged

Seen in clinic 11 Nov 2002


Excellent condition; walking independently and no
coordination problems and gained several Kgs
11 Nov 02
Course

19 Feb 2003

Acute confusion, weakness
19 Feb 2003
Ventriculoscopy
Course

Therapy
i.v voriconazole
 i.v liposomal AmB
 i.v Caspofungin
 Intra-ventricular Ampho B
 Intra-ventricular 5-FC

2 Apr 03
Course

Nothing helped and the patients died on 13
April 2003 after 3 years of “palliative” therapy
for disseminated Cladophialophora bantiana

Extensive immunological workup was negative
CID 2004:38 (15 January)
Revankar, et al. CID 39:206. 2004
101 cases

Cladophialophora bantiana accounted for 48 (48%)

Ramichloridium mackenzei, seen in 13 (13%)

Ochroconis gallopavum, seen in 5 (5%)
Continue,
Medical Therapy

Current agents
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AmB: typically resistant
Lipid AmB: limited experience
5-FC: Good in-vitro and in few cases with surgery
Itraconazole: good in vitro
Voriconazole: limited data. 2 cases of failure
Caspofungin: Resistant in vitro. No clinical data
Future
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Data only with posaconazole
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In vitro and animal
Future Therapy
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
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Posaconazole against C. bantiana in mice
Mice infected either intravenously or
intracranially with C. bantiana
Mice treated with posaconazole compare with
other antifungals
AAC 2005 (In press)
Survival of immunosuppressed ICR mice infected with
C. bantiana intravenously and treated with
amphotericin B (AMB) 3 mg/kg/day,
itraconazole 30 mg/kg three times daily and
posaconazole 30 mg/kg/day for 7 days.
100
80
% Survival
60
40
20
0
0
5
10
15
Days post infection
20
25
Control
AMB
Itraconazole
POS
Fungal burden (panel B) of immunosuppressed ICR mice infected with
C. bantiana intravenously and treated with
amphotericin B (AMB) 3 mg/kg/day,
itraconazole 30 mg/kg three times daily and
posaconazole 30 mg/kg/day for 7 days.
10
10
5
4
CFU/GM Brain
*
10
3
10
10
**
10
10
2
10
* p<0.001
** p<0.0001
Control
Ampho B
Itraconazole
Days post infection
POS
Survival of BALB/c mice infected with C. bantiana intracranially and treated with
posaconazole at a dose of 5, 15, 25, or 50 mg/kg/day for 28 days 2
starting at day one post infection.
100
80
% survival
60
40
20
0
0
5
10
15
Days post infection
20
25
CONTROL
POS 5MG
POS15MG
POS 25MG
POS 50MG