Aspergillosis patients support meeting. Speakers Pippa Newton and Graham Atherton

1. Support Meeting for
Aspergillosis Patients & Carers
LED BY GRAHAM ATHERTON
SUPPORTED BY
NAC CENTRE MANAGER CHRIS HARRIS
PSEUDOMONAS
PIPPA NEWTON
NATIONAL ASPERGILLOSIS CENTRE
UHSM
MANCHESTER
Fungal Research Trust

2. Programme
 1.30 Graham


New generation of antifungal medication
Itraconazole – anticancer drug?
 2.00 Tea & Coffee
 2.30 Pippa Newton (NAC Senior Consultant)

Pseudomonas – what is it, why does it make us ill?
 3.00 Q & A from the floor or online

3. Targets for attack
Targets to attack in the fungus MUST be only
present in the fungus, otherwise the drug would
attack the patient as much as it attacks the fungus
Different classes of drugs target the plasma
membrane, sterol biosynthesis, DNA biosynthesis,
and β-glucan biosynthesis

4. Fungal Cell Structure

5. What drugs do we have now?
Target
Antifungal
Sterol (Direct binding - Cell membrane)
Polyene group: Amphotericin B
Interfere with ergosterol synthesis
(Cell membrane)
Azole group: Itraconazole,
Voriconazole, Posaconazole
Allylamine group: terbinafine
Cell Wall
Glucan synthesis inhibitors:
Echinocandins:Caspofunfin,
Micafungin, Anidulafungin
DNA
Inhibits DNA synthesis: Flucytosine

6. Summary
We have already exploited 4 different targets to
attack fungi
Still a need to develop new drugs





Some against new targets
Some with better distribution
Lower toxicity
Fungicidal (more deadly)
Cheaper!!!

7. Great Progress
Macromolecular antimicrobial agents
(Nanomolecules)

8. Research Group
Fukushima et. al. 2013 (December)
Broad based research: US, China, Japan, Singapore
Research paper

9. History of this substance
Known for some time to be antimicrobial – works a
little like amphotericin B (Ambisome).

10. Toxicity
Just like amphotericin these new chemicals are known
to be toxic and lack specificity
They will attack human cell membranes just as much as
they attack microbial & fungal cell membranes
No good!

11. Polyene Binds sterol – (membrane)
Specificity - amphotericin

12. New form of molecule
Shows high specificity for fungal & bacterial cells
Leaves human cells alone!
Forms self aggregating assembly in water and targets
microbial cell membranes
Low toxicity to mammalian cells
Biodegradable
CHEAP to make in large quantities!!

13. Self aggregation

14. Disrupts cell membrane

15. Does it work in the lab?

16. Does it work on real infections?
Sections of eye infected with fungus
(Keratitis) and treated with:
Water
Amphotericin
New drug – note lack of toxicity

17. Human treatment?
Next phase is to test in humans – mainly as topical
treatment at first
Promising to provide a whole new class of drugs,
very difficult to develop resistance against
NB there is still little resistance to amphotericin after
55 years.

18. What is
Pseudomonas ?
Dr Pippa Newton

19. Pseudomonas related bacteria



Bacteria
Present in soil, plants and ground water
Several groups of Pseudomonas related bacteria that cause
disease
in humans including
- Pseudomonas aeruginosa
- Stenotrophomonas
- Burkholderia species

About 50% of the organisms grown
produce a blue-green pigment (pyocyan)

Detecting the bacteria in a clinical sample does not necessarily
mean there is an infection present

20. Colonisation versus Infection

Colonisation
- Pseudomonas present in clinical sample but it is not causing an
infection
- eg
present on normal skin
present in airways with no signs of
ongoing infection
- Patients colonised with Pseudomonas can later develop infection

Infection with Pseudomonas
- Clinical evidence of infection and sample taken from site of
infection grows Pseudomonas

21. Pseudomonas aeruginosa
infections

Usually causes infections in individuals with either chronic chest
problems or individuals with poor immune function

Can cause a variety of infections including
- Skin infections
- Surgical wound infections
- Chest infections
- Ear and sinus infections
- Urinary tract infections
- Bloodstream infections

Pseudomonas aeruginosa accounts for about 10% of hospital
acquired infections (often urinary and chest infections)

22. Skin and nail infections

Green nail syndrome
- If hands immersed in water for
prolonged periods of time

Skin
- Infected skin lesions – eg eczema, burns
- Blue-green discharge
- Swimming pool folliculitis

23. Urinary and Bloodstream
infections

Urinary infections
- Occur in patients who have had surgery or a catheter

Blood stream infections:
- Rare
- Pseudomonas
- Stenotrophomonas
2012
3,743 cases in E&W&NI in 2012
Commoner at the extremes of age
453 cases in E&W&NI in
Commoner is patients > 64 years old

24. Pseudomonas aeruginosa in the
lungs

Colonisation
- Tends to occur in individuals with chronic lung problems
- Eg
Bronchiectasis
Cystic Fibrosis (about 80% of patients are
colonised)

Chest infection symptoms
- productive cough – sweet / fruity odour
- more breathless / wheezing
- chest pain
- fevers
- loss of apetite
- weight loss

25. Investigations to determine
colonisation versus infection

Bloods:

Sputum culture: confirm the presence of pseudomonas and
once grown can test for antibiotic sensitivities
to look for evidence of ongoing infection
some patients have more than 1 strain of
pseudomonas in their sputum
and
Non mucoid
mucoid strains

26. Investigations to determine
colonisation versus infection

Chest X ray:
to look for signs of pneumonia

Blood culture:
to exclude infection in the blood in very
unwell patients

27. How do we treat Pseudomonas
aeruginosa in the lungs ?







Once Pseudomonas present it is very difficult to eradicate it
Best chance of eradicating Pseudomonas is early treatment
after initial detection in sputum
Only 1 oral antibiotic treats Pseudomonas – Ciprofloxacin
All the other antibiotics need to be given intravenously
Eradication treatment options
Control of Pseudomonas colonisation
Treatment of Pseudomonas infections

28. How do we treat Pseudomonas
aeruginosa in the lungs ?

Early eradication treatment options
- Oral ciprofloxacin and antibiotic nebulisers (Tobramycin,
Gentamycin, Colomycin)
- Intravenous antibiotics
- Treatment can be associated with improvements in lung
function tests

Colonised with Pseudomonas
- Antibiotic nebulisers used to keep down Pseudomonas
levels in sputum

29. How do we treat Pseudomonas
aeruginosa in the lungs ?

Treatment of Pseudomonas infection
- Oral ciprofloxacin (if Pseudomonas is sensitive to this)
- Combination of 2 intravenous antibiotics initially, then
consider reducing to 1 antibiotic once sensitivities of
Pseudomonas known

30. Stenotrophomonas

Tends to be found in watery environments

Usually results in colonisation rather than infection
- no treatment needed

Immunocompromised patients more likely to develop infections

Can cause the following infections
- Chest infections
- Urinary infections
- Long-term line infections

Treatment: Usually co-trimoxazole as a single agent

31. Regular cleaning of Nebulisers


Both Pseudomonas and Stenotrophomonas like watery
environments
Need to regularly clean home nebulisers to prevent bacterial
contamination

32. Summary



Pseudomonas related bacteria – concentrated on
Pseudomonas aeruginosa
- Different clinical infections that may occur
- Colonisation versus infection
- Treatment of colonisation and infections
Stenotrophomonas
Importance of keeping any home nebulisers regularly clean to
prevent contamination with these bacteria

33. Suggest a subject
Can be on any relevant subject you would like to hear
our opinion or get our help with
Send suggestions to admin@aspergillus.org.uk
Pass notes to me at clinic or at the meeting
Phone them in (24 hrs) at 0161 291 5866

34. Other advances
Stem cells proving to have the ability to help cure Tb!
(this was a surprise result – the experiment was only
intended to test for safety)

A group found that when they gave patients back their own
stem cells (patients who had infections that were resistant to
multiple drugs), three times as many as controls were cured
after 6 months!
Itraconazole may be useful to treat prostatic cancers!

35. Other news
Periodical for clinic is in development
An ‘expanded newsletter’ with news, information,
art, poetry. Probably do 4 editions.
Ideas welcome!

36. Thank You
“The best chance we have of beating this illness is to
work together”
Living with it, Working with it, Treating it
Fungal Infection Trust