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Fungal Research Trust supports launch of new anti-fungal drug
Patrons
Lord Turnberg of Cheadle
Mrs Nicola Horlick
Prof Stefan Buczacki
The Fungal Research trust are pleased to announce the long awaited launch
of Posaconazole (NoxafilR, Schering-Plough) in the UK. The world's first
studies showing the effect of this drug against Aspergillus infections were as
demonstrated in 1997 by studies funded by the Fungal Research Trust (FRT). In
particular, Aspergillus resistant to itraconazole was shown to respond to
Posaconazole. Approval for use in patients was granted for "Invasive
aspergillosis in patients refractory to/or intolerant of amphotericin B or
itraconazole."
Trustees
Dr Geoff Scott (Chairman)
Mr John Morgan (Secretary)
Mr Richard Gourlay
Mr Phillip Oxnam
Research Advisory Board
Prof Jacques Bille (Lausanne)
Prof David Denning
(Manchester)
Prof Roderick Hay (Belfast)
Dr Kenneth Haynes (London)
Prof Jack Sobel (Detroit)
Aspergillus species are a cosmopolitan very common air-borne fungus,
carried in the air all over the world as spores. Aspergillosis (the
diseases caused by Aspergillus) mainly affects the lungs and sinuses, but
can spread to other organs such as the brain. As well as leukaemia and bone
marrow transplant patients, 'invasive aspergillosis' is increasingly
affecting other immuno-suppressed hospital patient groups and is very
difficult to treat. Up to half of sufferers die of the condition, and as
many as 1 in 25 patients who die in modern European teaching hospitals are
now suffering from it. Other immuno-compromised patients such as those after
transplantation, with AIDS or leukaemia or on steroid treatment are increasingly
being affected with life-threatening Aspergillus pneumonia and sinusitis. Death
from fungal infection is a very disappointing outcome after successful
treatment of patients for underlying diseases.
Estimates of the numbers of patients in the UK in 2002 are shown in
this table.
Patient
The Fungal Research Trust is
responsible for
The Aspergillus website:
www.aspergillus.man.ac.uk
Number
(2002)
Bone marrow Tx
Solid organ Tx
Leukaemia
Solid tumour (neutropenic)
Advanced cancer
ICU
AIDS
Total
793
2,697
15,802
27,824
127,766
~200,000
<400
% invasive
aspergillosis
8.10%
2.2-2.8%
6.50%
1%
1.86%
3.62%
0.60%
The Fungal Research Trust
Charity No: 1003361
P O Box 482, Macclesfield, Cheshire, SK10 9AR, UK
Telephone No: 01625 500228
Website: www.fungalresearchtrust.org
Email: [email protected]
Range
2.8-15.1%
0.8-16.0(lung)%
2.0-9.6%
1 study only
1.3-2.2%
2.7-3.7%
0.02-4.0%
Expected
cases invasive
aspergillosis
64
62-78
1,027*
278
2,376*
7,240*
2
10,992
*Some double counting
To put these numbers in context, there are between 1000 and 2000 cases of
meningitis per year in the UK.
Posaconazole has advantages over previous drugs in being more active against
Aspergillus and other rarer moulds, has very few side-effects and many fewer
drug interference properties compared with other similar drugs.
The FRT's Scientific Advisor, Professor David Denning said, "Having seen
such powerful activity in 1997, it is gratifying that posaconazole has now
become available to treat patients. It will have a particular role in
preventing infection in leukaemia and after bone marrow transplantation. It
is the broadest spectrum antifungal now available."
Aspergillus can worsen asthma and cause allergic sinusitis in patients with
allergic tendencies, and can also get into lung cavities created by
tuberculosis (which affects a third of the world's population) causing
general ill-health and bleeding in the lung.
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For further information please contact :
June Beedham: 0771 432 6527
Prof. David Denning: 078024 82193
12 May 2006
NOTE TO EDITORS: The Fungal Research Trust (www.fungalresearchtrust.org) is
a registered charity which funds research into and education about fungal
infection. It was set up in 1991 and since then has distributed in excess of
£1.6m in research grants resulting in more than 80 research publications in
clinical and scientific aspects of fungal infection. It also supports the
Aspergillus Website which achieves around 160,000 page requests a month. As
well as being a key resource for clinicians, the website also devotes a
section to patients and relatives to help them understand more about the
disease. It can be found at www.aspergillus.man.ac.uk.
What is fungal disease?
There are 4 broad groups of fungal infections in man (fungi are the main cause of
plant disease as well). Fungal infections can be grouped as follows:




Thrush (ie vaginal thrush, oral thrush (AIDS and cancer patients, antibiotic
treatment) and severe nappy rash)
Skin infections ie athlete’s foot, ringworm, dandruff, cradle cap, nappy
rash and nail infections
Invasive and life-threatening infection ie candidiasis (intensive care,
prematurity, leukaemia, diabetes, dialysis), invasive aspergillosis
(leukaemia, transplantation and steroid treatment) and cryptococcal
meningitis (AIDS)
Allergic fungal disease ie allergic fungal sinusitis (normal people with
chronic sinusitis) and allergic bronchopulmonary aspergillosis (asthma
and cystic fibrosis) and severe asthma with fungal sensitisation
Common fungi
Common fungi causing disease are:
Candida albicans (thrush and invasive candidiasis)
Aspergillus fumigatus (allergic fungal disease and invasive aspergillosis)
Trichophyton interdigitale (athlete’s foot and nail infections)
About 30 different species of fungi cause the vast majority of human fungal
infection. In all about 600 species out of an estimated 1 million species worldwide
cause human infection; others are implicated in allergic disease.
Fungal Research Trust papers
Efficacy of SCH-56592 (posaconazole) in a temporarily
neutropenic murine model of invasive aspergillosis with an
itraconazole-susceptible and an itraconazole-resistant isolate
of Aspergillus fumigatus.
Oakley KL, Morrissey G, Denning DW.
Department of Medicine, Hope Hospital, Salford, and University of
Manchester, United Kingdom.
Antimicrob Agents Chemother. 1997 Jul;41(7):1504-7.
SCH-56592 (SCH) is a novel triazole antifungal agent with excellent in
vitro activity against Aspergillus. We compared three doses (5, 10, and 25
mg/kg of body weight) of SCH with itraconazole (ITZ; 25 mg/kg) and
amphotericin B (AB; 5 mg/kg) in a temporarily neutropenic murine model
of disseminated aspergillosis (lungs and kidneys) against one ITZsusceptible (AF71) and one ITZ-resistant (AF90) isolate of Aspergillus
fumigatus. Treatment started 24 h after infection and lasted for 10 days.
Dosing regimens for SCH were once daily for 10 days, those for ITZ were
three times daily for 2 days and then twice daily for 3 to 10 days, and
those for AB were once daily on days 1, 2, 4, and 7. Both isolates killed
90% of control mice. Kidneys and lungs from survivors were cultured on
day 11. Against AF71, all three doses of SCH and ITZ yielded a 90 to
100% survival rate and AB yielded 40% survival (P < or = 0.01 to 0.0001
for all treatment groups compared with the controls). All three doses of
SCH were superior to AB in cultures of lung and kidney tissue samples (P
< or = 0.01 to 0.0002) and SCH at 25 mg/kg was superior to ITZ in
cultures of kidneys (P = 0.01). Against AF90, the highest dose of SCH (25
mg/kg) resulted in a 100% survival rate, compared with 60 and 20%
survival rates for the groups treated with SCH at 10 and 5 mg/kg,
respectively. Treatment with ITZ yielded no survivors. AB therapy
achieved a 50% survival rate. SCH at 25 mg/kg (P < 0.001), SCH at 10
mg/kg (P < or = 0.005), and AB (P < 0.05) were superior to ITZ in cultures
of lungs and kidneys. There was a correlation between the MICs of SCH
and quantitative organ culture results and between the minimum fungicidal
concentration of AB with quantitative organ culture results. SCH appears
to be a highly effective anti-Aspergillus compound in this model. There
appears to be a degree of cross-resistance between itraconazole and
SCH.
PMID: 9210674
In vitro activity of SCH-56592 (Posaconzole) and comparison
with activities of amphotericin B and itraconazole against
Aspergillus spp.
Oakley KL, Moore CB, Denning DW.
Department of Medicine, Hope Hospital, Manchester, United Kingdom.
Antimicrob Agents Chemother. 1997 May;41(5):1124-6.
In this study, we investigated the in vitro activity of SCH-56592 (SCH), a
new triazole antifungal agent. We compared the activity of SCH with those
of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of
Aspergillus spp. by using a microtiter format. Incubation was done at 37
degrees C for 48 h, and MIC endpoints (no growth) were read visually.
The medium used for all of the drugs was RPMI 1640 buffered with
morpholinepropanesulfonic acid (MOPS) and supplemented with 2%
glucose. MICs and minimum fungicidal concentrations (MFCs; killing of >
or = 99.99%) were measured for all isolates. The geometric mean (GM)
MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09
and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32.
Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM,
0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8
microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per
milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125
to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32,
and 64% of the isolates against which SCH, ITZ, and AB, respectively,
were tested were killed. A reproducibility study was performed with 20% of
the isolates; for 11 of the 12 isolates retested, the MIC was the same or
within 1 well of the original MIC of each drug. Therefore, in vitro mould
testing of SCH is feasible and reproducible. SCH was found to be very
active against all species of Aspergillus and at lower concentrations than
either ITZ or AB.
PMID: 9145880
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