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Treatment of chronic MRSA infections using a novel aqueous extract of Allicin (AB1000)
Ronald R. Cutler 1, Peter D. Josling 2 and Norman J. Bennett 2
(1.) School of Health and Bioscience, University of East London, UK. (2.) Allicin International, Rye , UK.
Allicin is recognised as the main bioactive agent from Allium sativum or garlic.
This compound is highly active but generally unstable. Using a cold aqueous
extraction method, we have obtained a novel extract of allicin (AB1000) that we
have reported is stable and highly active in vitro against methicillin resistant
Staphylococcus aureus (MRSA).
Due to national publicity of AB1000, patients with long standing unresolved MRSA
infections requested this agent for treatment. MRSA is commonly related to
delayed closure for many chronic and acute wounds. This is associated with high
levels of bacteria in tissues but they can also through toxin secretion. These
toxins can cause local necrosis and disrupt the delicate balance of critical
mediators such as cytokines and proteases necessary for healing progression.
We present initial findings from three patients who have completed a course of
treatment. These courses consisted of capsules (450mg , 3 per day ); spraying
liquid AB1000 (1000 ug ml-1) onto the affected areas once per day and applying
AB1000 Cream (500 ug ml-1) to the infected area once daily.
Patients were screened, nasal and wound for MRSA prior and during treatment.
All patients were nose and wound swab MRSA positive prior to treatment. All
were over 60 years of age and had either major surgery or long term skin
infections leading to the formation of ulcers infected by MRSA. Two of the MRSA
infections were community acquired and one hospital acquired. The strains
isolated from each patient were tested in vitro against AB1000 and all were
susceptible.
Patients reported an improvement in their condition after 2 and 6 weeks treatment
and the infections resolved in 3 to 4 months.
Although the timescales required for treatment may be longer than those normally
required using antibiotics, the initial relief from weeping ulcers and pain was much
quicker. It should be noted these the patients had been receiving unsuccessful
treatment with antibiotics for months or years prior to treatment with AB1000. A
possible reason for the initial relief from symptoms could relate to the reported
activity of garlic extracts to neutralise bacterial exoenzymes in vitro. This could
account for the findings that patients got relief from their symptoms before the
MRSA were fully removed from the lesion site.
Background
MRSA is still a major cause of nosocomial infections. There
is a need for new topical and systemic antibiotics that may
help in controlling and treating MRSA infections (1). MRSA is
often linked to delayed closure for chronic and acute wounds
associated with high levels of bacteria in tissues and toxin
secretion by the bacteria. Patients report weeping lesions for
months or years despite treatment with conventional
antimicrobial agents.
We have previously reported the in vitro effectiveness of a
novel stabilised form of allicin (AB1000) against MRSA (2).
The main antimicrobial effect of allicin may be due to its
reaction with the thiol-containing enzymes. In this study we
investigate the use of AB1000 in neutralizing microbial
enzymes in an attempt to explain the results from volunteer
studies in people with long-term chronic MRSA infections.
Methods
Results
Enzyme studies:
Enzyme Studies:
The effect of AB1000 at different concentrations on
the in vitro activity of microbial alcohol dehydrogenase
(ADH), a thiol containing enzyme important in alcohol
metabolism, was examined. A range of concentrations
of AB1000 were pre-incubated with ADH and the
ability of the enzyme to catalyze the transfer of a
hydride from the hydroxyl carbon of either ethanol or
allyl alcohol to NAD. This was determined using
spectroscopy (340nm-measuring the conversion of
NAD+ to NADH)
After 60 minutes pre-incubation with 250ug/ml of
allicin the activity of ADH was reduced by 31% using
ethanol as a substrate and by 36% with allyl alcohol.
We also demonstrated that ADH activity was related to
the concentration of allicin used in pre-treatment (
Figure 1)
Volunteer Studies:
People who had chronic weeping lesions infected with
MRSA volunteered to use topical and systemic
treatment with AB1000 cream, liquid and capsules.
These patients had long term MRSA infections and
had been unsuccessfully treated with antibiotics.
Volunteers were given full information on AB1000 and
were asked to discuss the treatment with their clinician
prior to taking part in the study.
Absorbance (340nm)
Abstract
0.9
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0
100
200
Ethyl alcohol
Allyl alcohol
•Liquid AB1000 spray (1000 mg/l) to be used in the
morning spraying onto the infected areas.
Volunteer Studies:
Patients were screened, nasal and wound for MRSA
prior and during treatment.
Patients tested their skin for sensitivity prior to use
and were told to stop use if at anytime there was any
sign of irritation related to the use of AB1000.
All were over 60 years of age and had either major
surgery or long term skin infections leading to the
formation of ulcers infected by MRSA.
Conclusions
Allicin m g/l
Figure 1: Activity of ADH after treatment with AB1000
•AB1000 capsules (450mg) , to be used 3 times per
day ;
Figure 3: Picture on the left
shows weeping inflamed
lesions (before allicin
treatment). The picture on
the right shows that the
lesions have dried and are
healing after 3 months treatment. Patient is MRSA free.
300
Volunteers were supplied with:
•AB1000 cream (500 mg/l) to be applied once per day
in the evening onto the infected areas.
Figure 2: Pictures of leg wounds before and after 2
months treatment. The left picture shows a red inflamed
weeping lesion (before allicin treatment). The right
shows the inflammation has reduced and the lesion is
healing.
The initial results from volunteer studies showed all
patients were nose and wound swab MRSA positive
prior to treatment. Two of the MRSA infections were
acquired in nursing homes and one was hospital
acquired. The strains isolated from each patient were
tested in vitro against AB1000 and all were
susceptible.
Patients reported an improvement in their condition
after 2 and 6 weeks treatment.
This included reduction in pain, redness, irritation and
swelling. (Figure 2).
Infections resolved in 3 to 4 months (Figure 3).
Patients reported an improvement in their condition after 2
to 6 weeks treatment and the infections resolved in 3 to 4
months. Although the timescales required for treatment are
longer than those normally required using antibiotics, the
initial relief from weeping ulcers and pain happened in
weeks. It should be noted these the patients had been
receiving unsuccessful treatment with antibiotics for
months or years prior to treatment with AB1000.
One possible reason for the initial relief from symptoms
could relate to ability of Allicin to neutralise thiol-containing
enzymes, demonstrated here. The potential to reduce the
activity of extra-cellular virulence factors could account for
the findings that patients got relief from their symptoms
before the MRSA were fully removed from the lesion site.
References
1.
Schmitz, F and Jones ME. Antibiotics for treatment of infections
caused by MRSA and the elimination of MRSA carriage. What are
the choices? Int. J. Antimicrob. Agents, 1997; 9: 1-19.
2.
Cutler, RR, Wilson,P. Antibacterial activity of a new, stable,
aqueous extract of allicin against methicillin-resistant
Staphylococcus aureus. Brit. Jour. Biomed. Sci. 2004, 61:71-74