Phytochemicals

australia’s gift to the world

Eugene Sherry OR Design Unit, Univ Sydney

Patrick H Warnke Univ Kiel, Germany

Univ. of Kiel, and Univ.Sydney
52 yo Female/SAm/TA repair with
wound breakdown at 3 months…
PT used daily

DAY DAY DAY

ONE 12 28
 MRSA FACTS
 MRSA infection rates in Europe and USA are as high as 30% in ICU. [Geldner G,
Ruoff M, Hoffman H.-J, Georgieff M, Wiedeck H, Cost Analysis - MRSA - ICU
Department of Anaesthesiology, University of Ulm, Germany]
 Average monthly cost of MRSA patient = 9408 EURO[Geldner G, Ruoff M,
Hoffman H.-J, Georgieff M, Wiedeck H, Cost Analysis - MRSA - ICU Department of
Anaesthesiology, University of Ulm, Germany]
 New York City Hospitals cost per MRSA patient up to US $35,300 [Rubin RJ,
Harrington CA, Poon A, Dietrich K, Greene JA, Moiduddin A, The Economic
Impact of Staphylococcus aureus Infection in New York City Hospitals, Emerging
Infectious Diseases, Vol 5(1)1999]
 The additional cost imposed on the US health system annually by antibiotic
resistance has been estimated to range between US $100 million and US $30 billion.
[Hellinger WC, Confronting the problem of Increasing Antibiotic Resistance, South
Med J 93(9): 842-848, 2000][Phelps CE: Bug/drug resistance. Sometimes less is
more. Med Care 1989; 27:194-203]
 Australia-(approx) (AUD)$4B@ year; 40,000 joints @ year; 300 hospitals
 Resistance has developed and increasing in Vancomycin "the drug of last resort",
presenting Doctors with no other antibiotics to treat infection. [Gilliland KK, Flores
PA, Gordon SM, Vancomycin-Resistant Staph: Epidemiology and Therapeutic
Options; Infect Med 17(4):289-298, 2000]
 Vancomycin Hcl has many side effects including difficulty breathing, weakness,
Ototoxicity, Tinnitus and drug induced Nephrotoxicity.[First DataBank, USA]
 HISS study
• Study of Hospital Acquired Infections
• CABG 1.3%
• Vascular surgery 7.3%
• Hip prosthesis 0.5%
• Knee prosthesis 9.8%
• LSCS 2.3%
• Colorectal 12.7%
 Extrapolations from HISS MRSA data to NSW
Surgical Patients

•
• Type of Hospitals Total Number of Infected Surgical Patients / Surgical
separations for 1 year
• Principal Referral 355/ 126,707
• Major Metropolitan 71/50855
• Major Non-Metropolitan 7/33093
• Total 433 / 210655 surgical patients

• = 2.1 per 1000 surgical patients

• Mean cost1 per patient $32,362
• Total Cost for NSW Principal referral, Major Metropolitan and Non-metropolitan
hospitals $14 million per year
• .National Surveillance of healthcare Associated Infection in Australia: A Report
to
• the commonwealth Department of health and Aged Care prepared by the Expert
• Working Group of Australian Infection
 Sustainability science within a divided world
(Sustainability Science RW Kates et al, Science 292 27 April, 2001 p641-2)

• North
• Old,rich millions
• Affluence
• “Global people”
• Resource surpluses
• Technological knowledge
• Theory-driven research
• South
• Young,poor billions
• Poverty
• “Local people”
• Resource shortages
• Impacts of climate
changes
• Traditional knowledge
• Action-driven research
“The AIDS problem is so devastating that what you want
is answers now and understanding later”
(Maurive Hilleman,veteran vaccinologist. Science 4 May 2001 p 862)

• Out of Africa (old)-

• “Africa is home to most every infectious agent that has ever plagued
humans”. (John Cohen. Shots in the Dark. Science 4 May 2001 p 862)

• From Australia (new)-

• Blue Mountains. National Park. One Million Hectares Eucalyptus
• ? Place of Healing.
 Phytochemicals
• Eucalyptus Oil- KLONEMAX

• Tea-Tree Oil-

• Combination
 ONE SUCH PRODUCT: Polytoxinol

-antimicrobial liquid,
-complex formulation of plant extracts,
-strongly bactericidal in vitro against a broad range of aerobic
bacteria,including methicillin resistant Staphylococcus aureus
(MRSA),
- other constituents that are anti-inflammatory and promote healing
(product information, listed in MINS, p 312 Dec 2000 issue)
-TGA licensed
-German Commission E approves internal use and steam
inhalation/American Herbal Products Assoc-class 2d safety
rating
-Licensed through the General Sale List in UK
 Antisepsis history
• OW Holmes(19th C) • Sir W MacEwen
• Semmelweis,Vienna, • Sir John
• high maternal sepsis Charnley(1911-82)
rate • Florey,penicillin,huma
• Lister(1827-12), n trials 1941
12/8/1865 sprayed • 2001 FAILURE of
carbolic acid over antibiotics:only
wound during surgery vancomycin/animal
use/synercid Nature 411
p 513 2001;
• ZYBOX lasted 12 mths
 Activities of eucalyptus oil
• -antibacterial-all bacteria, incl pseudomonas & MRSA.
• -antifungal, anti-mycosis. Candida, aspergillus( HIV)
• -anti-inflammatory
• -anti-cancer. Skin and pulm tumours in mice.
• -liverprotective
• -anti-plaque
• -pain reliever

• see handout(documented in literature/PubMed)

 Other plant derivatives
• Aspirin(bark of willow tree)

• Digitalis(foxglove)

• KloneMax…………………….
 Administration
• Liquid(spray)
• Cream
• SW-Inhaler S(inhalational):Pneumocystis
carinnii (HIV and Immunodefic) &
Pseudomonas aeruginosa (HIV, Cystic
Fibrosis).Patented Product available.
• beads(calcium crystal carrier)
 (possible) KloneMax application via SW-
Inhaler S in respiratory tract infections

• Warnke PH(1), Sherry E(2), Polzhofer GK(3), von Engeln K(4),

Schuenemann H(5)

• 1: Dept of Oral- and Maxillofacial Surgery, University of Kiel,

Germany
2: Dept of Orthopedic Surgery, University of Sydney, Australia
3: Dept of Dermatology, University of Kiel, Germany
4: Dept of Otorhinolaryngology, Head- and Neck Surgery, Univ of
Heidelberg,
Germany
5: Cosmas-Pharmacie, Barssel, Germany
 biofilm, KM is a slimebuster

• Bacterial grow on surfaces in slimy

microbial cities, 1000x more resistant

• KM can ?penetrate these films,unlike other

antimicrobial agents(nature 408 16 nov
2000 p284-6)

• K+-membrane leakage in E.coli

 Vancomycin-resistant staph

aureus reported in Australia

• MJA 175 5 Nov 2001 p 480-483

 TB FACTS
• TB infects 2 billion people worldwide [Butler D, Consortium Aims to
Kickstart TB Research, Macmillan Publishers 2000]
 Resistance to drugs for the treatment TB is increasing [Hellinger WC,
Confronting the problem of Increasing Antibiotic Resistance, South Med J
93(9): 842-848, 2000][Pablos-Mendez A, Raviglione MC, Laszlo A, et al:
Global surveillance for antituberculosis-drug resistance 1994-1997. WHO -
International Union against Tuberculosis and Lung Disease Working Group
on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med 1998;
338:1641-1649]
 There are 8 million new cases, and two million deaths each year from TB.
[Butler D, Consortium Aims to Kickstart TB Research, Macmillan Publishers
2000]
 WHO Director-General, " it is high time to find new and more effective
drugs"[Butler D, Consortium Aims to Kickstart TB Research, Macmillan
Publishers 2000]
 In 1998, it is estimated 10 million people died from Infectious diseases.
[Weinstein RA, Talkpaper, 40th Interscience Conference on Antimicrobial
Agents & Chemotherapy, Medscape Inc.
 No new drug has been developed for the treatment of TB for 30 years.
 Treatment of TB involves many drugs and hospitalisation and high costs.
 • TB FACTS

 TB infects 2 billion people worldwide [ Butler D, Consortium Aims to Kickstart TB

Research, Macmillan Publishers 2000]

 WHO estimates there will be 90 million new cases and 30

million deaths by 2010, and if current infection rates and
treatment trends go unchanged, 70 million more people
will die between now and 2020. [New drug eases TB treatment, American Medical News, Vol.
41, No. 28, July 27, 1998]

 South-East Asia constitutes the biggest burden in TB

control worldwide www.stoptb.org]
[World TB Day 2001, Fact Sheet,

 Treatment costs around US $2500 per patient, rising to

US $250,000 in multi drug resistant TB, with the overall
potential cost of lost productivity due to TB is in the order
of 4%-7% of GDP(same ref).
 TB facts ctd
 Resistance to drugs for the treatment TB is increasing.
– [Hellinger WC, Confronting the problem of Increasing Antibiotic Resistance,
South Med J 93(9): 842-848, 2000][Pablos-Mendez A, Raviglione MC, Laszlo A, et
al: Global surveillance for antituberculosis-drug resistance 1994-1997. WHO -
International Union against Tuberculosis and Lung Disease Working Group on
Anti-Tuberculosis Drug Resistance Surveillance. N Engl. J Med 1998; 338:1641-
1649]
 There are 8 million new cases, and two million deaths
each year from TB. [Butler D, Consortium Aims to
Kickstart TB Research, Macmillan Publishers 2000
 WHO Director-General, " it is high time to find new and
more effective drugs".
– [Butler D, Consortium Aims to Kickstart TB Research,
Macmillan Publishers 2000]
 comment from AJIC, 3 July, 2001
• > "This paper presents a provocative
hypothesis that an oil extract of the
> Australian trees Eucalyptus globulus...,
which is active against Mycobacterium
tuberculosis in vitro
> may be of value in the treatment of
tuberculosis
 KloneMax challenged
against Mycobacterium terrae
Nov, 2001

• 10 ml product challenged with 1 ml M.terrae. At each

exposure time, 1 ml of mixture was subcultured into 99 ml
neutraliser and plated out for surviving organisms. 0.1ml
of the neutralised suspension was spread on pre-poured
plate,giving a final sensitivity level of < 1000 cfu
M.terae/ml.
 results
Contact 10 mins 20 mins 30 mins 40 mins
time

Day 14 1.2 x 10 5.4 x 10 2.0 x 10 8.0 x 10

6 5 5 3

Recovery 10%
M.terrae