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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 ONE DAY 12 DAY 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 Vascular surgery Hip prosthesis Knee prosthesis LSCS Colorectal 1.3% 7.3% 0.5% 9.8% 2.3% 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) • Semmelweis,Vienna, • high maternal sepsis rate • Lister(1827-12), 12/8/1865 sprayed carbolic acid over wound during surgery • Sir W MacEwen • Sir John Charnley(1911-82) • Florey,penicillin,huma n trials 1941 • 2001 FAILURE of antibiotics:only 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 SWInhaler 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 [
Research, Macmillan Publishers 2000] Butler D, Consortium Aims to Kickstart TB

 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]  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).
[World TB Day 2001, Fact Sheet,

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; 338:16411649]

 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 time Day 14

10 mins 20 mins 30 mins 40 mins 1.2 x 10 5.4 x 10 2.0 x 10 8.0 x 10
6 5 5

3

Recovery M.terrae

10%