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American Journal of Ethnomedicine, 2014, Vol. 1, No.

1, 018-029
Available online at http://www.ajethno.com
© American Journal of Ethnomedicine

Antimicrobial Activity of Medicinal Plant


Extracts and Their Synergistic Effect on Some
Selected Pathogens
Desalegn Amenu*

College of Natural and Computational Science, Biology Department, Wollega


University, P. O. Box, 395, Ethiopia

ABSTRACT

Antibiotics provide the main basis for the therapy of microbial (bacterial and
fungal) infections. Since the discovery of these antibiotics and their uses as
chemotherapeutic agents there was a belief in the medical fraternity that this
would lead to the eventual eradication of infectious diseases. There is a
continuous and urgent need to discover new antimicrobial compounds with
diverse chemical structures and novel mechanisms of action because there has
been an alarming increase in the incidence of new and re-emerging infectious
diseases. Another big concern is the development of resistance to the antibiotics
in current clinical use. In recent years, drug resistance to human pathogenic
bacteria has been commonly reported from all over the world. In the present
scenario of emergence of multiple drug resistance to human pathogenic
organisms, this has necessitated a search for new antimicrobial substances from
other sources including plants. Higher plants produce hundreds to thousands of
diverse chemical compounds with different biological activities. The
antimicrobial compounds produced by plants are active against plant and human
pathogenic microorganisms. It is expected that plant extracts showing target sites
other than those used by antibiotics will be active against drug-resistant microbial
pathogens.

Keywords- Herbal extracts, Antimicrobial agent, Multi-drug resistant.

INTRODUCTION infections, toxic shock syndrome,


endocarditis, osteomyelitis and food
The development of bacterial resistance to poisoning5. Gram negative bacterium such
presently available antibiotics has as Escherichia coli is present in human
necessitated the need to search for new intestine and causes lower urinary tract
antibacterial agents. Gram positive bacteria infection, coleocystis or septicaemia6.
such as Staphylococcus aureus are mainly Multiple drug resistance in human
responsible for post-operative wound pathogenic microorganisms has been

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American Journal of Ethnomedicine

developed due to indiscriminate use of aeruginosa strains resistant to different


commercial antimicrobial drugs commonly antimicrobial agent classes. Perhaps, this
used in the treatment of infectious diseases. high degree of multidrug resistance related
The development of antibiotic resistance is to the presence of antibiotic efflux systems
multi factorial, including the specific nature which provide resistance to multiple
of the relationship of bacteria to antibiotics, antimicrobial agents3.
the usage of antibacterial agent, host Multidrug-resistant Entero-
characteristics and environmental factors. bacteriaceae, mostly Escherichia coli,
This situation has forced scientists to search produces extended-spectrum β lactamases-
for new antimicrobial substances from M (ESBLs) enzymes. These enzymes
various sources as novel antimicrobial suchwere as the named for their greater
chemotherapeutic agents, but the cost activity against cefotaxime as other
production of synthetic drugs is high and oxyimino-beta-lactam substrates such as
they produce adverse effects compared to ceftazidime, ceftriaxone, or cefepime have
plant derived drugs2. emerged within the community setting as an
These antimicrobial substances are important cause of urinary tract infections
of natural origin, and it is thought that their (UTIs). Recent reports have also described
influences on the environment are few and ESBL-producing E. coli as a cause of
can be used as biological control agents. bloodstream infections associated with these
However, some medicinal herbs for some community-onsets of UTI12. Some
reasons have not found wider application Palestinian plants exhibit significant potency
and sometimes are referred as ‘forgotten against human bacterial pathogens.
plants’. Even though pharmacological However, at present, plant extracts are rarely
industries have produced a number of new used as antimicrobials or as a systemic
antibiotics in the last three decades, antibiotics and this may be due to their low
resistance to these drugs by microorganisms level of activity, especially against gram-
has increased. In general, bacteria have the negative bacteria3.
genetic ability to transmit and acquire Wadi Gaza is an essential part of
resistance to drugs, which are utilized as natural life in Palestine and has a rich
therapeutic agents10. biodiversity in terms of fauna and flora. As
From these microbes resistant to many as 70 plant species belonging to 32
antibiotics, Methicillin-resistant Staphy- families and 24 orders were identified in
lococcus aureus (MRSA) is a major cause of Wadi Gaza. The aster or daisy family
nosocomial infections. MRSA infections are (Compositae) is the largest found family
very difficult to cure because MRSA strains which composed of 14 plant species (20%)
are resistance against almost all clinically of the recorded species. The natural flora of
available antibiotics. For most MRSA Wadi Gaza was commonly used in different
strains, glycopeptide-type drugs such as ways as a source of food, herbal medicine,
vancomycin are the only effective anti- fodder for grazing animals, timber and fuel
microbial agents. However, vancomycin- production1.
resistant S. aureus (VRSA) has been
reporte3. Pseudomonas aeruginosa also Objective
causes nosocomial infections as a result of To assess the antimicrobial and
its ubiquitous nature, ability to survive in synergistic effect of some medicinal plant
moist environments and resistance to many extracts with antibiotic and non-antibiotic
antibiotics and antiseptics. A main problem drugs against isolates E. coli, S. aureus and
is the emergence of multidrug-resistant P. P. aeruginosa.

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considered an integral part of the Palestinian


LITERATURE REVIEW culture and plays a pivotal and indispensable
role in the current public healthcare. The
Medicinal plants hills and mountains of Palestine are covered
Plants as a source of medicinal with more than 2600 plant species of which
compounds have continued to play a more than 700 are noted for their uses as
dominant role in the maintenance of human medicinal herbs or as botanical pesticides19.
health since ancient times. According to the The following are some of the
World Health Organization plant extracts or medicinal plants that have been studying its
their active constituents are used as folk effect against some clinically isolated
medicine in traditional therapies of 80% of bacteria.
the world drugs are of natural product
origin22. Nerium oleander
The specific function of many In history this plant has been used in
phytochemicals is still unclear; however, a medicine. It is popularly used as an
considerable number of studies have shown ornamental plant, for its evergreen nature.
that they are involved in the interaction of Although it's toxic to human and animals,
plants/pests/diseases. Antimicrobial but it is also proved to contain medicinal
screening of plant extracts and phyto- value like antibacterial activity and Anti-
chemicals, then, represents a starting point inflammatory activity, and with these
for antimicrobial drug discovery. Phyto- considerations, this plant is now being
chemical studies have attracted the attention studied for its uses medicine with caution 22.
of plant scientists due to the development of All parts of the plant are poisonous, from
new and sophisticated techniques. These roots to stems, from leaves to flowers and
techniques played a significant role in the seeds, including the smoke if we try to burn
search for additional resources of raw them. Many experiments have been made in
material for pharmaceutical industry33. time, and there is now common knowledge
Medicinal plants possess that chewing or simply biting the leaves a
immunomodulatory and antioxidant couple of times can lead to severe
properties, leading to antibacterial activities. intoxication (in extreme cases followed by
They are known to have versatile death), that even dry leaves are toxic, that
immunomodulatory activity by stimulating cattle, horses and sheep being
both non-specific and specific experimentally poisoned have died, etc.
32
immunity .The use of plant extracts and Humans have even died after eating meat42.
phytochemicals, both with known The leaves and the flowers are
antimicrobial properties, can be of great cardiotonic, diaphoretic (is excessive
significance in therapeutic treatments. In the sweating commonly associated with shock
last few years, a number of studies have and other medical emergency conditions),
been conducted in different countries to diuretic, anticancer, antibacterial, antifungal
prove such efficiency. Many plants have and expectorant. And also the flowers,
been used because of their antimicrobial leaves, leaf juice, bark and roots have been
traits, which are due to compounds used against corns, warts, cancerous ulcers,
synthesized in the secondary metabolism of carcinoma, ulcerating or hard tumors 41. The
the plant29. root is better; aphrodisiac, tonic good for
In Palestine, there are numerous chronic pain in the abdomen and pain in the
medicinal plants described for treatment of joints, very poisonous, but an antidote to
many diseases. Herbal medicine is snake-venom. The juice of the young leaves

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is poured into eyes in ophthalmia with Withania somnifera


copious lachrymation16. Withania somnifera belongs to
Essential oils and their components Solanaceae family commonly known as
are widely used in medicine as constituents Ashwagandha/Indian ginseng/winter
8
of different medical products, in the food cherry .
industry as flavouring additives and also in The main active constituents of
cosmetics as fragrances and pharmaceutical Withania somnifera are steroidal lactones,
industries and also are generally used in the alkaloids, flavonoids, tannin etc. The major
cosmetic, medical and food industries. The chemical constituents of these plants, with
essential oil of Nerium oleander has been anolides, are mainly localized in leaves21.
the object of several studies antifungal, Numerous studies indicated that
antibacterial, molluscicidal, antioxidant, anti ashwagandha possesses antioxidant,
hyperglycemic, antifungal, cytotoxial and antitumor, antistress, anti-inflammatory,
insecticidal activity14. immunomodulatory, hematopoetic, anti-
ageing, anxiolytic and also influences
Artemisia herba-alba various neurotransmitter receptors in the
The genus Artemisia L. (family central nervous system. In recent studies
Asteraceae, tribe Anthemideae), comprises a done on human breast, lung and colon
variable number of species from 200 to over cancer cell lines, plant extracts inhibited the
400, (depending on the authors) found growth of these cell lines35. Its roots, leaves
throughout the northern half of the world. and seeds are used in Ayurvedic and Unani
The genus may be divided into sections medicines, to combat diseases ranging from
Artemisia and Dracunculus26. tuberculosis to arthritis. The pharma-
The genus Artemisia is known to cological activity of the plant is attributed to
contain many bioactive compounds; the presence of several alkaloids and
artemisinin exerts not only antimalarial withaniols. Roots are prescribed in
activity but also profound cytotoxicity medicines for hiccup, several female
against tumor cells and arglabin is employed disorders, bronchitis, rheumatism, dropsy,
for treating certain types of cancer22. stomach and lung inflammations and skin
Artemisia is used for the treatment of diseases. Its roots and paste of green leaves
diabetes mellitus in Iraq, and for are used to relieve joint pains and
hypertension and diabetes in oriental inflammation. It is also an ingredient of
Morocco. Many Artemisia species have a medicaments prescribed for curing disability
high economic value in several fields, as and sexual weakness in male. Leaves are
food plants and as antihelminthic and used in eye diseases. Seeds are diuretic. It is
antimalaria in medicine. This species of a constituent Lactare’ which of is the
sagebrush is widely used in folk and galactagogue20. Also have several medicinal
traditional medicine for its antiseptic, properties such as sedative, hypotensive,
vermifuge and antispasmodic properties. aphrodisiac, bradycardiac, respiration
Artemisia herba-alba was reported as a stimulatory, antiperoxidative, cardiotonic,
traditional remedy of enteritis, and various radiosensitizing and thyro-regulatory
intestinal disturbances, among the Bedouins effects9.
in the Negev desert. In fact, essential oil Beside its use as general tonic. And
showed antibacterial activity, as well as, several recent reports have demonstrated
antispasmodic activity on rabbits39. immunomodulator (also known as an
immunotherapy is a substance (e. g. a drug)
which has an effect on the immune system)

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and antitumor effect of ashwagandha as antifungal, expectorant, anti-septic, anti-


well31. histamine16.
And has a long folklore history as a
Ficus sycomorus treatment for cold, cough and asthma and is
The Sycamore Belongs to family reported to strengthen the immune system. It
Moraceae is one of the old and historic plant has many medicinal effects such as lowering
species in the Palestine coastal valley and of blood cholesterol level, antiplatelet
the study area as well. The trees have some aggregation, anti-inflammatory activity and
medicinal values as the sap extracted from inhibition of cholesterol synthesis37.
the trunk can cure some skin diseases 1 The Different garlic extracts demon-
active principles of many drugs found in strated activity against Gram negative and
plants are secondary metabolites. These Gram-positive bacteria including species of
secondary metabolites which constitute an Escherichia, Salmonella, Staphylococcus,
important source of the pharmaceutical Streptococcus, Klebsiella, Proteus, Bacillus,
drugs have been isolated from different parts clostridium, Helicobacter pylori and even
of plants. Some of these compounds have acid-fast bacilli (AFB) such as
been reported to be present in the Ficus Mycobacterium tuberculosis. Allicin is
species such as tannins, saponins, thiosulfinate compound of garlic reported
flavonoids, steroids, anthraquinone for its antibacterial activity. Allicin is
glycosides and reducing sugars. Ficus proved to be anti-bacterial as it inhibits
sycomorus have been suspected to possess RNA synthesis16.
anti-diarrhoeal activities and sedative and
anticonvulsant (are a diverse group of Eucalyptus camaldulensis
pharmaceuticals used in the treatment of Eucalyptus camaldulensis is an
epileptic seizures) properties of this plant important ethnomedicinal plant belonging to
have also been reported30. Reported different the family Myrtaceae. There are more than
solvent extracts of some plants to have 700 species that comprise this genus, most
different pharmacological properties. are native of Australia, though they are also
Reported organic stem extracts of F. widely cultivated throughout the tropics,
sycomorus with higher antifungal activity especially in Asia and Central America as
than aqueous extracts17. The fruit extracts of well as Africa6. Are used in China folk
Ficus sycomorus L exhibited antitumor medicine for a variety of medical conditions.
activity in the potato disc bioassay. it had For examples, hot water extracts of dried
significant antibacterial activity, but no leaves used as analgesic, anti-inflammatory
antifungal activity28. and antipyretic remedies for the symptoms
of respiratory infections, such as cold, flu,
Allium sativum and sinus congestion. and also known to
Allium sativum; commonly known as contain bioactive products that display
garlic, is a species of the onion family antibacterial, antifungal , analgesic and anti-
Alliaceae. Allium sativum is a natural plant inflammatory effects and anti oxidative
being used as a food as well as folk activities10. Some studies have demonstrated
medicine for centuries in all over the world, that the oil and leaf extracts of Eucalyptus
in 1996, Reuter et al. described garlic a plant spp. have antifungal and repellent activity.
with various biological properties like Crude methanolic extract of E.
antimicrobial, anti-cancer, antioxidant. As Camaldulensis has been reported to inhibit
well as different properties such as antiviral, the growth of Candida albicans. Also, it has
been shown that ethanolic leaf extract of

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Eucalyptus camaldulensis had marked Escherichia coli Infections


fungicidal effect against clinical Escherichia coli was initially
dermatophytic fungal isolates; Micro- considered a non-harmful member of the
sporium gypseum and Trichophyton men- colon flora, but is now associated with a
tagrophytes15. wide range of diseases and infections
including meningeal, gastrointestinal,
The bacteria urinary tract, wound and bacteremia
Clinical isolated bacteria used in the infections in all age groups24. Other
study are Escherichia coli, Pseudomonas infections caused by Escherichia coli
aeruginosa and Staphylococcus aureus. include peritonitis, cholecystitis, septic
wounds and bedsores. They may also infect
Escherichia coli the lower respiratory passages or cause
bacteraemia and endotoxic shock especially
Classification in surgical or debilitated patients25.
Escherichia coli is the most
commonly encountered member of the Antimicrobial Susceptibility
family Enterobacteriaceae in the normal Within the community, Escherichia
colonic flora and the most common cause of coli strains are commonly susceptible to all
opportunistic infections. All members of the agents active against the Enterobacteriaceae.
family Enterobacteriaceae are facultative, all However, because of the frequent
ferment glucose and reduce nitrates to occurrence of R plasmids, strains acquired
nitrites and all are oxidase negative36. in hospitals may be resistant to any
combination of potentially effective
Morphology and identification antimicrobics and therapy must therefore be
Escherichia coli is gram-negative, guided by susceptibility testing36.
non-sporing bacilli with most strains being
motile and generally possessing both sex pili Staphylococcus aureus
and adhesive fimbriae24. Because most
strains rapidly ferment lactose, colonies Classification
grown on MacConkey media are smooth, Members of the genus
glossy, and translucent and are rose-pink in Staphylococcus (staphylococci) are Gram-
colour. Some strains grown on blood agar positive cocci that tend to be arranged in
result in colonies being surrounded by zones grape-like clusters33.
of haemolysis. Colonies are smooth,
circular, 1 –1, 5 mm in diameter and yellow Morphology and identification
opaque if lactose fermenting (blue, if non- Staphylococci are spherical cells
lactose fermenting) when grown on cystine- about 1 m in diameter arranged in irregular
lactose-electrolyte deficient (CLED) clusters. Single cocci, pairs, tetrads, and
medium25. chains are also seen in liquid cultures.
Young cocci stain strongly gram-positive;
Epidemiology on aging, many cells become gram-negative.
Strains of Escherichia coli Staphylococci are non-motile and do not
predominate among the aerobic commensal form spores7. Staphylococcus aureus is a
bacteria present in the healthy gut25. facultative anaerobe that grows at an
optimum temperature of 37ºC and an
optimum pH of 7, 5. S. aureus produces
white colonies that tend to turn a buff-

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golden color with time, which is the basis of Antimicrobial Susceptibility


the species epithet aureus (golden). Most, Resistance to penicillin G can be
but not all, strains show a rim of hemolysis predicted by a positive test for β-lactamase;
clear surrounding β the colony (Ryan and approximately 90% of S aureus produce β-
Ray, 2004). On nutrient agar, following lactamase. Resistance to nafcillin (and
aerobic incubation for 24 hours at 37ºC, oxacillin and methicillin) occurs in about
colonies are 1 – 3mm in diameter, have a 35% of S. aureus and approximately 75% of
smooth glistening surface, an entire edge S. epidermidis isolates7. Alternative
and an opaque pigmented appearance. In antibiotics for resistant organisms (e.g.
most strains, pigmentation is golden with MRSA) include vancomycin, erythromycin
orange, yellow and cream varieties. On Mac and gentamicin. Some strains become
Conkey agar, colonies are small to medium resistant to multiple antibiotics18.
in size and pink or pink-orange in colour25.
Pseudomonas aeruginosa
Epidemiology
Staphylococci are highly successful Classification
colonizers of humans and animals. They Pseudomonas aeruginosa is a
reside mainly on the skin, particularly in classic opportunist pathogen belonging to
moist areas such as the anterior nares (nose), the genus Pseudomonas25.
axilla and groin. Between one-third and
three-quarters of individuals carry these Morphology and Identification
organisms at any one time. Staphylococcal Is obligate aerobe, motile, rod-
infections occur worldwide and newly shaped, and measuring about 0.6 x 2 µm. It
emerging hyper virulent or multi resistant is gram-negative and occurs as single
strains spread rapidly over wide bacteria, in pairs, and occasionally in short
geographical areas. The bacteria survive in chains. Sometimes producing a sweet or
the air, on objects or in dust for days, grape like or corn taco-like odor (Brooks et
therefore they can contaminate al., 2007). Its production of blue, yellow, or
environments (such as hospitals) and rust-colored pigments differentiates it from
continue to be transmitted over long periods most other Gram-negative bacteria. The blue
of time. Some individuals may shed the pigment, pyocyanin, is produced only by P.
organism more heavily than others. aeruginosa. Fluorescin, a yellow pigment
Staphylococcal infections are acquired from that fluoresces under ultraviolet light is by
either self (endogenous) or external P. aeruginosa and other free-living less
(exogenous) sources18. pathogenic Pseudomonas species.
Pyocyanin produced and fluorescin
Infections combined produce a bright green color that
S. aureus causes serious infections of diffuses throughout the medium (Ryan and
the skin, soft tissues, bone, lung, heart, brain Ray, 2004). P aeruginosa grows well at 37–
or blood18. Include pneumonia, bacteremia 42 °C; its growth at 42 °C helps differentiate
leading to secondary pneumonia and it from other Pseudomonas species. It does
endocarditis, osteomyelitis secondary to not ferment carbohydrates, but many strains
bacteremia and septic arthritis, seen in oxidize glucose7.
children and in patients with a history of
rheumatoid arthritis. Diseases caused by Epidemiology
Staphylococcal toxins include scalded skin P. aeruginosa normally inhabit soil,
syndrome and toxic shock syndrome36. water, and vegetation and can be isolated

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from the skin, throat, and stool of healthy antibiotics are crucial not only for the
persons. They often colonize hospital food, treatment of bacterial infections, but also for
sinks, taps, mops, and respiratory prophylactic coverage of high risk patients
equipment. Spread is from patient to patient e.g. those in intensive care, organ
via contact with fomites or by ingestion of transplants, cancer chemotherapy and
contaminated food and water4 prenatal care. However, these gains are now
seriously jeopardised by the rapid
Infections emergence and spread of microbes that are
Pseudomonas aeruginosa causes resistant to antimicrobials (www.earto.eu).
infections in healthy individuals and those The mass production of penicillin in
who are hospitalized or have a compromised 1943 dramatically reduced illness and death
immune system as a result of other diseases. from infectious diseases caused by bacteria.
A variety of human infections are commonly However, within four years, bacteria began
associated with this bacterium: Urinary tract appearing that could resist the action of
infections, Ventilator-associated pneumonia, penicillin. Pharmaceutical companies fought
Surgical site infection, Respiratory back by developing other types of
infections, Ocular infections, Ear infections antibiotics. After more than 50 years of
(external otitis, malignant external otitis), widespread use of these “miracle drugs”, as
Skin and soft tissue infections, including hot effective as they anti-biotics once was.
tub folliculitis, and osteomyelitis and Burn Virtually all important bacterial infections in
sepsis Individuals with compromising throughout the world are becoming
conditions, such as HIV/AIDS, cystic resistant20. And even though
fibrosis, chemotherapy-related neutropenia, pharmacological industries have produced a
and diabetes have an increased risk of number of new antibiotics in the last three
acquiring an infection and developing decades, resistance to these drugs by
complications38. microorganisms has increased. In general,
bacteria have the genetic ability to transmit
Antimicrobial Susceptibility and acquire resistance to drugs, which are
Pseudomonas aeruginosa is utilized as therapeutic agents29.
frequently resistant to many commonly used
antibiotics. Although many strains are Methicillin-resistant Staphylococcus aureus
susceptible to gentamicin, tobramycin, (MRSA)
colistin, and amikacin, resistant forms have Methicillin-resistant Staphylococcus
developed, making susceptibility testing aureus (MRSA) is a major cause of
essential4. nosocomial infections. MRSA infections are
very difficult to cure because MRSA strains
Antibiotic resistance are resistance against almost all clinically
The discovery of antibiotics in the available antibiotics1. MRSA infections that
mid-twentieth century revolutionized the are acquired by persons who have not been
management and treatment of infectious recently hospitalized or had a medical
disease caused by bacteria. Infections that procedure (such as dialysis, surgery and
would normally have been fatal were now catheters) are known as Healthcare
curable. Since then, antimicrobial agents associated MRSA (HA MRSA) first
(antibiotics and related medicinal drugs appeared in the 1960s and has typically been
acting on bacteria, viruses, fungi and linked to persons with health care associated
parasites) have saved the lives and eased the risk factors such as hospitalization or
suffering of millions of people. Today, nursing home care, chronic dialysis,

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antibiotic treatment, or exposure to invasive bloodstream infections associated with these


devices or procedures. HA MRSA is a community-onsets of UTI12.
highly resistant and important nosocomial
pathogen in both acute care and long term CONCLUSION
care settings and causes infections
associated with increased morbidity, On the basis of the antibacterial
mortality, and cost when compared to assay of this study S. aureus was found the
infections due to susceptible strains of S. more (susceptible to the employed plant
aureus11. Beginning in the 1990s community extracts) than E. coli and P. aeruginosa.
associated MRSA (CA MRSA) infections All plant extracts were evaluted for
emerged in persons having none of the risk their MIC against E. coli, S. aureus and P.
factors associated with MRSA in the past. areuginosa, The MIC value for each of
CA MRSA is currently defined as an methanolic extract of E. camaldulensis
infection with MRSA in a person who does against E. coli was 3.125 mg/ml. And the
not have any prior history of a health care methanol and aquatic extract of F.
exposure such as hospitalization, surgery, sycomorus (leaves) against S. aureus was
permanent intravenous lines or other from 6.25-3.125 mg/ml. And the ethanol
indwelling devices, or hemodialysis13. extract of E. camaldulensis against P.
areuginosa was 6.25 mg/ml. Suggesting that
Multi drug resistant Pseudomonas very small amount of the extracts are
aeruginosa required to inhibit the growth of the bacteria
Pseudomonas aeruginosa also thus E. camaldulensis (methanol extract),
causes nosocomial infections as a result of leaf extract of F. sycomorus (methanol and
its ubiquitous nature, ability to survive in aquatic extract) and E. camaldulensis
moist environments and resistance to many (ethanol extract) had very potent activity
antibiotics and antiseptics. A main problem against E. coli, S. aureus and P. areuginosa,
is the emergence of multidrug-resistant P. respectively.
aeruginosa strains resistant to different Ethanolic plant extracts were showed
antimicrobial agent classes. Perhaps, this antimicrobial and synergistic activity with
high degree of multidrug resistance related antibiotics better than methanolic and
to the presence of antibiotic efflux systems aquatic extracts. The strongest effect agaist
which provide resistance to multiple E. coli was recorded when F. sycomorus
antimicrobial agents1. (leaves and bark) were mixed with
Ofloxacin. And the strongest effect on S.
Multi drug resistant Enterobacteriaceae aureus was observed when A. sativum was
Multidrug-resistant Entero- combined with Ofloxacin and Tetracyclin.
bacteriaceae, mostly Escherichia coli, The strongest effect against P. areuginosa
produces extended-spectrum β lactamases- was observed when Ceftazidime was
M (ESBLs) enzymes. These enzymessuch combined with most plant extracts,
were as th named for their greater activity especially with F. sycomorus (leaves and
against cefotaxime than other oxyimino- bark); when the extracts of N. oleander, A.
beta-lactam substrates such as ceftazidime, herba-alba and W. somnifera were
ceftriaxone, or cefepime have emerged combined with Amikacin and also when the
within the community setting as an extract of W. somnifera and L. camara were
important cause of urinary tract infections mixed with Neomycin.
(UTIs). Recent reports have also described Vitamin C alone did not show any
ESBL-producing E. coli as a cause of antibacterial activity against all tested

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bacteria. It is likely that used distilled water 3. Adwan. G, Abu-Shanab, B and Adwan. K
as solvent has reduced the effectiveness it. (2009). In vitro Interaction of Certain
Paracetamol showed antibacterial activity Antimicrobial Agents in Combination with
against S. aureus and P. aeruginosa, Plant Extracts against Multidrug-resistant
especially at a concentration of 10 µM Pseudomonas aeruginosa Strains. Middle-
East Journal of Scientific Research Vol.4
(inhibited zone=11mm). Loperamide Hcl (3): 158-162.
was showed antibacterial activity against S. 4. Baron. S (1996). Medical Microbiology, 4th
aureus, P. aeruginosa and E.coli, at a edition. The University of Texas Medical
concentration of 100 µM, 10 µM and 10 Branch at Galveston, Texas.
µM, respectively (inhibited zone= 12, 13 5. Benayache. S, Benayache. F and Benyahia.
and 12, respectively). The synergistic S (2001). Leaf Oils of some Eucalyptus
activity of plant extracts and Non-antibiotic Species Growing in Algeria. J. Essent. Oil
drugs was the best among the aqueous Res., 13: 210-213.
extracts of L. camara and each of 6. Benhassaini. H and enabderrahmane. K and
Paracetamol, loperamid Hcl and vitamin C Chi. K (2003). Contribution to the
against E. coli. As well, the best synergistic assessment of the antiseptic activity of
essential oils and oleoresin of Pistacia tial
activity among the aqueous extracts of A. Atlas on some microbial sources: Candida
herba-alba and each of Paracetamol and albicans (ATC 20027), Candida albicans
loperamid Hcl was against S. aureus. And (ATCC 20032) and s accharomyces
the best synergistic activity was observed cerevisiae: ethnopharmacology, February
between N. oleander and Paracetamol (at a (30): 38-46
concentration of 50 and 10µM) against P. 7. Brooker, M.I.H., Connors, J.R., Slee, A.V.
aeruginosa. and Duffy, S. (2002) EUCLID: eucalypts of
Regards the synergistic activity southern Australia (CD Rom), CSIRO
between the antibiotics and non-antibiotic Publishing, Collingwood.
drugs, the best synergistic activity was 8. Chatterjee, S., et al., 2010. Comprehensive
recorded between Ampicillin and each of metabolic fingerprinting Withania somnifera
leaf and root extracts. Phytochemistry 71,
paracetamol and loperamide HCL against S. 1085–1094.
aureus, and among Nalidixic acid and each 9. Chaurasia. S, Panda.S and Kar. A (2000).
of paracetamol and loperamide Hcl. In Withania somnifera Root Extract in The
addition synergistic activity was observed Regulation of Lead-Induced Oxidative
with Co-trimoxazole and each of Damage in Male Mouse. Pharmacological
paracetamol and loperamide Hcl against E. Research, Vol. 41, No. 6.
coli; Amikacin and paracetamol and 10. Cheng. S, Huang. C, Chen. Y, Yu. J, Chen.
loperamide Hcl against P. aeruginosa. W and Chang. S (2009). Chemical
compositions and larvicidal activities of leaf
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