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Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats


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In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the most widely spread
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DOI 10.1515/pjvs-2016-0067
Original article
Efficacy of topical therapy with newly developed
terbinafine and econazole formulations
in the treatment of dermatophytosis in cats
M. Ivaskiene
, A.P. Matusevicius
, A. Grigonis
, G. Zamokas
, L. Babickaite
Laboratory of Experimental and Clinical Pharmacology, Department of Non-Infectious Diseases,
Lithuanian University of Health Sciences, Veterinary Academy, Tilzes 18, LT-47181 Kaunas, Lithuania
Dr. L Kriauceliunas Small Animal Clinics, Lithuanian University of Health Sciences, Veterinary Academy
In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring
infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The
aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment
of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole
formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the
most widely spread Microsporum canis-induced dermatophytosis and treated with terbinafine hydro-
chloride 1% cream, recovered within 20.3±0.88 days; whereas when treated with econazole nitrate 1%
cream, they recovered within 28.4±1.14 days. A positive therapeutic effect was yielded by combined
treatment with local application of creams and whole coat spray with enilconazole 0.2% emulsion
„Imaverol”. Most cats treated with econazole cream revealed redness and irritation of the skin at the
site of application. This study demonstrates that terbinafine tended to have superior clinical efficacy
(p<0.001) in the treatment of dermatophytosis in cats compared to the azole tested.
Key words:cat, terbinafine, econazole, cream, dermatophytosis
Dermatophytosis, also known as tinea or ring-
worm, is a disease caused by superficial fungal infec-
tion of the skin with a propensity to attack hair shafts
and follicles. It is caused by fungi of the genera Micro-
sporum,Trichophyton and Epidermophyton. Besides
humans, it may affect rodents, dogs, cats, horses,
cattle and swine. Dermatophytes are classified as zo-
ophilic, mainly found in animals, but can be passed to
humans. Anthropophilic dermatophytes are mainly
Correspondence to: M. Ivaskiene, e-mail:, tel.: +370 69934060
found in humans and are passed to animals rarely.
Geophilic dermatophytes are found mainly in soil,
where they feed on decomposing hair, feathers,
hooves and other sources of keratin. They infect both
humans and animals. Dermatophytosis is very con-
tagious and spreads extremely quickly among humans
and animals. This disease is the most commonly oc-
curring dermatological zoonosis. Over 90% of feline
dermatophytosis cases worldwide are caused by
Microsporum canis (Seebacher et al. 2008, Frymus et
al. 2013).
Polish Journal of Veterinary Sciences Vol. 19, No. 3 (2016), 535–543
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Today dogs and cats have become the most popu-
lar pets in the world, and suit our lifestyle perfectly.
As a result, it is common for people to be in close
contact with pets, who often happen to suffer from
zoonosis. There is an increasing amount of publica-
tions focusing on the superficial and invasive mycosis
that spread among people (Skerlev and Miklic 2010).
Microsporum canis is the most common agent in
et al. 2008).
Pets are frequently blamed for the transmission
of dermatophytes between animals and humans.
Transmission between hosts usually occurs by direct
contact with a symptomatic or asymptomatic host, or
direct or airborne contact with its hairs or skin scales.
Infective spores in hair and dermal scales can remain
viable from several months to years in the environ-
ment. Skin lesions in both humans and animals are
usually characterized by inflammation that is the
most severe at the edges, with erythema, scaling and
occasionally blister formation. Lesions can be localiz-
ed or generalized, usually pruritic in humans, not
animals, with burning sensation. Dermatophytes that
are acquired from animals or soil generally cause
more inflammatory lesions in humans than an-
thropophilic dermatophytes (Ameen 2010). Al-
though, dermatophyte infections may be self-limiting
in the individual with a strong immune system and
good living condition, the treatment helps to ex-
pedite the resolution of the disease and minimize the
risk for infected spores to spread into the environ-
ment (Scott et al. 2001). Topical therapy is intended
for animals with dermatophytosis, and may be the
sole therapy for local, non-diffuse lesions (Moriello
Although mycoses are widespread, for a long
time there was a limited choice of effective and
non-toxic antifungal agents used for treatment (Van-
den Bossche et al. 2003). Polyenes and pyrimidine
derivatives were available for the treatment of my-
coses; however, their limited antifungal spectrum
and toxicity to mammalian cell diminished their use
(Maertens 2004). The continued search for new and
less toxic antifungals led to the discovery of the
imidazoles, the modification of which led to the de-
velopment of more potent triazoles and bistriazoles.
During the last decades, a new group of allylamines
has been synthesized. The antifungal action of al-
lylamines is mediated by inhibition of ergosterol bio-
synthesis at a site much earlier in the pathway than
the azole antifungal drugs (Matusevicius et al.
2008a,b). Allylamines are highly selective for the
fungal enzyme and have a minimal effect on mam-
malian cholesterol synthesis, thus are more effective
and less toxic to mammalian cell than azoles. Over
the past years, there have been a variety of trials
evaluating use of topical terbinafine addressing dif-
ferent pharmaceutical formulations. Terbinafine is
very well tolerated in any topical pharmaceutical for-
mulation and also has high efficacy as a cure for der-
matophytosis in humans, irrespective of type of phar-
maceutical formulation, treatment duration and fre-
quency of application (Korting et al. 2007). Recently,
econazole and terbinafine are widely used in antifun-
gal preparations for human mycoses, however these
agents are not licensed for use in animals. Although
terbinafine is prescribed for the treatment of my-
coses in humans, it is increasingly being used in vet-
erinary patients (Sakai et al. 2011). In Lithuania,
available topical formulations for use in pets are
(miconazole) and Imaverol
(enilconazole), which contain antifungals of first
generation imidazole, that are fungistatic, have nar-
row spectrum of activity and the development of re-
sistance to these antifungals has become increasingly
therapy, which decreases the time of treatment and
owner’s exposure to the disease, is important in vet-
erinary medicine.
Materials and Methods
Newly developed formulations
The Laboratory of Experimental and Clinical
Pharmacology in Veterinary Academy of Lithuanian
University of Health Sciences has prepared two topi-
cal formulations, E-1 and T-1, to treat pets infected
with dermatophytosis. Both topical formulations in
the form of cream are developed on the basis of ho-
mogeneous oil-in-water emulsion. The vehicle of for-
mulations contains chemical substances, which are
safe and commonly used in topical preparations.
These substances are: salicylic acid, mono-
ethanolamine and chloralhydrate. The formulation
E-1 contains antifungal active agent belonging to
imidazole group – econazole nitrate (1%); T-1 for-
mulation contains agent belonging to allylamine
group – terbinafine hydrochloride (1%). Formula-
tions have to spread easily and dry rapidly on ani-
mal’s skin, leaving no detectable residue and adher-
ing to the treated area without being tacky, having
optimal pH and being non-irritating to the skin, as
well as having no unpleasant texture or odour, but
having keratolytic and moisturizing effect on skin.
The aim of this study was to determine the clinical
efficacy of newly designed topical formulations E-1
and T-1.
M. Ivaskiene et al.536
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Scientific research was conducted according to the
Act No. B1-639 of the Republic of Lithuania, dated
18/12/2008, Regarding Animal Care, Storage, Main-
tenance and Use („Valstybes zinios”, 22/01/2009, No
8). The treatment was performed by the pet’s owner
upon signing the consent. Effectiveness and safety of
experimental creams were assessed in 40 cats (random
age and gender) with M. canis naturally induced der-
matophytosis that had from one to five clearly ex-
pressed skin lesions with a diameter of less than 5 cm.
Microsporum canis was identified in 86 damaged skin
sites. The majority (n=45; 52.3%) of damaged skin
sites was determined in the head and muzzle areas.
Limb area of damaged skin amounted to 33.7%
(n=29), body area amounted to 11.6% (n=10) and
tail area amounted to 2.3% (n=2).
Animal treatment
The cats were divided into 4 experimental groups
(A, B, C, D), each containing 10 animals. The cats had
similar intensity of infection – extensive damage to the
skin, erythema, crusting, ulceration, loss of hair.
Group A was treated with cream T-1 only, group
B was treated with cream E-1 only, group C and
D were treated with experimental creams – T-1 and
E-1, respectively and additionally with enilconazole
0.2% emulsion „Imaverol” spray every 3 days until the
end of clinical changes.
A pea-sized portion (average 25 mg) of experi-
mental cream was used for one application. Skin
lesions were treated with experimental creams two
times a day, in the morning and in the evening, by
rubbing it gently into the affected area before the
feeding time, or Elizabethan collars were used to pre-
vent cats from grooming. The lesions were visually
examined daily throughout the experiment to deter-
mine the severity and recovery of lesion. The animal
was considered to have recovered completely, when
the hair in the damaged area had fully grown back,
there were no signs of infection and the mycological
test result was negative.
Clinical evaluation
Changes in lesion scaling, erythema, ulceration or
alopecia were examined and recorded daily. To evalu-
ate the clinical efficacy, the methodology described by
Ghannoum et al. (2009) was used. The infected area
was divided into four equal quadrants. Each quadrant
was scored on a scale from 5 to 0 as follows: 5 – exten-
sive damage to the skin, redness, crusting, ulceration,
loss of hair; 4 – erythematous skin, loss of hair, scal-
ing; 3 – slightly erythematous skin, moderate scaling,
hair starts to re-grow, few bald patches; 2 – no
erythema, no swelling, hair re-grows over entire lesion
site, little scaling; 1 – no erythema, no scaling, hair is
half length long; 0 – absence of lesion, no signs of
infection, hair is fully re-grown. These scores were
summed for the four sites on each animal and were
used to compare the efficacy of different treatments.
Treatment efficacy in percents was calculated using
the following equation: Efficacy = 100 (T*100/C),
where T – the total score of treated lesion in each
animal; C – the score of 20 for the unhealed lesion.
The total score for any group denotes the average
clinical score from different animals in the same
Mycological examination
Cats infected with Microsporum canis were identi-
fied at admission via physical examination and pres-
ence of skin lesions. Visual diagnosis was approved by
performing standardised mycological test. Damaged
hairs were plucked with sterile tweezers from the de-
marcation zone between healthy and damaged skin,
scabs and dandruff were collected. The sample from
each animal was divided into two parts. One part was
cultivated under aerobic conditions in a thermostat at
C, another part was cultivated under aerobic con-
ditions in a thermostat at 37
C. Samples were placed
on the Sabouraud Dextrose Agar in Petri dishes, incu-
bated for up to 7 days and examined daily. Fungal
identification was based on cultural morphology and
microscopic examination of hyphae, microconidia and
macroconidia. Lactophenol Cotton Blue Solution was
used as mounting medium and staining agent in the
preparation of slides for microscopic examination of
fungi. Mycological test was repeated after clinical
signs of infection disappeared. MacKenzie’s tooth-
brush technique was also used to ensure spores had
not remained on the coat.
Data and statistical analyses
Statistical analysis of data was performed using
SPSS statistical package (version 15, SPSS Inc.,
Chicago, IL). Mean total (±SE) (SE – standard error)
of treatment days was calculated for each treatment
group. The groups were compared by a time-to-event
analysis (survival analysis). The Log Rank
(Mantel-Cox) test was used to compare the survival
time. Student test Independent Samples T Test was
Efficacy of topical therapy with newly developed terbinafine... 537
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Fig. 1. Clinical efficacy of tested formulations.
Fig. 2. Distribution of healing time according to the treatment used.
M. Ivaskiene et al.538
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applied to evaluate the differences between effective-
ness of treatments. P value <0.05 was considered sig-
Figure 1 shows comparative clinical percent effi-
cacy of each tested formulation. First signs of recovery
were seen on the second day of treatment in animals
of group A and C, while group B and D showed recov-
ery signs on the third day of the treatment. Cats, suf-
fering from Microsporum canis-induced derma-
tophytosis, when treated with cream T-1 (group A),
have recovered in 20.3±0.88 days (15-24 d.); whereas,
when treated with cream E-1 (group B), they have
recovered in 28.4±1.14 days (23-33 d.). During this
research, two groups of cats with localized skin lesions
were treated with experimental creams and ,Imaverol`
solution. Such a combined treatment of local applica-
tion of cream T-1 and whole coat spray with
„Imaverol” solution (group C) yielded positive thera-
peutic effect in 21.8±1.15 days (16-28 d.), whereas lo-
cal application of cream E-1 and whole coat spray
with „Imaverol” solution (group D) yielded positive
therapeutic effect in 28.1±0.97 days (24-34 d.). The
difference between mean treatment time of groups A,
C and B, D was statistically significant (p<0.01). The
probability of recovery over the time is shown in Fig.
2. Treatment with the cream T-1 reached the prob-
ability 1 faster (all treated animals recovered). This
was followed by the combined treatment of cream T-1
and „Imaverol” spray, cream E-1 and ultimately by
combined treatment of cream E-1 and „Imaverol”
spray. Treatment with T-1 and „Imaverol”, E-1 and
„Imaverol” demonstrated clinical efficacy after
6.6±1.5 and 8.7±1.2 applications, respectively. This
study demonstrates that treatment with the cream T-1
influence the healing rate statistically significantly
(p<0.001) compared to the treatment with cream E-1
and combined treatment with cream E-1 and
„Imaverol” solution. During observational period of
12 months, all the cats did not show disease recur-
rence. Figures 3-8 show the lesions on the right cheek
and the right side of the neck of the 2 year old cat
treated with the cream T-1 and recovered in 15 days.
Over the past decade, the effectiveness and tolera-
bility of terbinafine were actively investigated in the
treatment of animal dermatomycoses (Bechert et al.
2010, Sakai et al. 2011, Williams et al. 2011, Wang et
al. 2012). After a number of studies in animals, scien-
tists have proved that orally administered terbinafine
is effective in the treatment of cats suffering from ex-
perimentally induced or naturally occurring derma-
tophytosis (Castanon-Olivares et al. 2001, Kotnik
2002, Kotnik and Cerne 2006, Foust et al. 2007). Re-
cently topically applied terbinafine showed superior
effectiveness in the treatment of experimental M. can-
is infection in guinea pigs (Ivaskiene et al. 2011).
In the present study, treated cats had a similar
level of infection intensity; but the time of the disap-
pearance of the clinical symptoms varied. It was no-
ticed that lesions began recovering rapidly after crusts
and infected hairs, both of which are the food source
of dermatophytes, were removed. Presumably this
happened due to everyday moisturizing effect on skin,
which speeds up the cleansing of the lesion and helps
to recover skin barrier properties. It was noticed that
after the crust is gone and the hair had fallen off, it is
easier for the pharmacological formulation to reach
the stratum corneum and the microscopic fungi pres-
ent within. Therefore, after such „cleansing” the
lesion heals and the hairs start to grow back.
During the research most cats treated with cream
E-1 revealed redness and irritation of the skin at the
site of application. The animals have been starting to
scratch the patch of skin, which the cream was applied
to, immediately after application; however, the irrita-
tion would disappear after couple of hours. It is
known that azoles used in topical formulations may
cause side effects, such as skin itching, redness and
burning sensation (Sheppard and Lampiris 2007).
According to printed sources, dermatophytosis is
a common infectious skin disease among small ani-
mals. Dermatophytosis is highly contagious and
zoonotic; therefore its treatment has to be effective,
convenient, safe and inexpensive. When treating
cutaneous fungal infections in pets, topical drugs are
often preferred to oral drugs. The efficacy of a topical
drug depends on the nature of the vehicle and the
physicochemical properties of its active substance.
A higher oral dose usually needs to be administered
to achieve the same local concentration of a drug,
which increases the risk of side effects (Ozcan et al.
2009). The preferred form for a topical administration
of an active substance is cream and lotion, which are
usually homogeneous oil-in-water emulsions, or „van-
ishing creams” that have a continuous aqueous phase
containing oily globules. Oil-in-water emulsions in-
tensely hydrate the skin. Increased skin hydration
opens the structure of the superficial layers of the
skin, which in turn increases the penetration of active
agents (Benson 2005). The evaporation of water pro-
vides a cooling effect on the skin (Williams 2003).
It is a common knowledge that emollients, moist-
urizers and keratolytic agents are central to the topi-
Efficacy of topical therapy with newly developed terbinafine... 539
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Figs. 3, 4, 5. Lesions on the first day of treatment with cream T-1.
M. Ivaskiene et al.540
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Figs. 6, 7. Lesions after 7 days of treatment with cream T-1.
Fig. 8. Skin recovered after 15 days of treatment with cream T-1.
Efficacy of topical therapy with newly developed terbinafine... 541
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cal treatment of the skin diseases. They are supple-
mentary to classic treatments and help normalize bar-
rier function of the stratum corneum; they suppress
anti-inflammatory effects and make the epidermis
more resistant to external stress factors. Salicylic acid
is generally used in ointments and solutions because
of its antiseptic, keratolytic and antipruritic proper-
ties; it increases hydration and softens the stratum cor-
neum by decreasing its pH. Topical salicylates im-
prove the absorption and productiveness of other
topical medications (Yosipovitch et al. 2001). More-
over, the pH of creams was adjusted to 6.2, because
reduction in skin pH suppresses the reproduction of
pathogenic microbiota (Matousek et al. 2003).
The present results concur with those of previous
studies, which demonstrated high effectiveness of
topical terbinafine formulations in the treatment of
experimental dermatophytosis in guinea pigs (Ghan-
noum et al. 2004, 2009, 2010).
Allylamines and azoles are lipophilic drugs; they
usually accumulate in the stratum corneum and hair
follicles, and persist there at concentrations above the
MIC for several weeks after a short-term therapy (Jes-
sup et al. 2000, Foust et al. 2007). Absorption of
lipophilic drugs into the bloodstream is very low after
topical application (Schafer-Korting et al. 2008). Pre-
sumably that was the reason the mycological test and
toothbrush technique results were negative to all the
cats at the end of the treatment after all clinical signs
of infection disappeared.
This study demonstrated that terbinafine tended
to have superior clinical efficacy compared to the
azole tested. This apparent superiority may be due to
the fungicidal activity and non-skin irritating proper-
ties of terbinafine compared to the fungistatic and ir-
ritating effect of the econazole. The inhibiting fungi-
cidal activity of terbinafine, keratolytic and hydration
effect of newly designed oil in water formulation allow
reaching fast results of treating dermatophytosis in
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... Dermatophytosis is a zoonotic disease caused by fungal infection of a species of dermatophyte [1,2]. Dermatophytosis is more commonly known as ringworm, which is macroscopically characterized by multifocal alopecia and crust on the skin with a specific formation [3,4]. ...
... Dermatophytosis is more commonly known as ringworm, which is macroscopically characterized by multifocal alopecia and crust on the skin with a specific formation [3,4]. This disease is distributed globally and has gained special attention in public health [2,5]. Dermatophyte infections in humans occur after contact with contaminated products or specimens, such as soil, hair, or crust on the epidermal layer of infected animals [5]. ...
... In Europe, the incidence of dermatophytosis in dogs and cats ranges from 20 to 30% [8]. The results of various studies concluded that the main species causing dermatophytosis in pets is Microsporum canis, in 81.8%-97% of the cases [1,2,6]. The incidence of zoonotic dermatophytes M. canis was the highest in dogs, cats, and human (60.0%) compared to other species [9]. ...
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Dermatophytosis, a zoonotic disease, is caused by fungi of three main genera, namely, Micropsorum, Trichophyton, and Epidermophyton. Specific lesions of dermatophyte infections are localized in the face, legs, and/or tail. Skin lesions in infected animals demonstrate localized alopecia, erythema, and crust, which are more commonly known as ringworm. Factors that affect dermatophytosis include the dermatophyte species; virulence factors of the agent; and the immune status, age, and sex of the host. High levels of cortisol and pro-inflammatory cytokines have also been reported to play an important role in dermatophyte infection. This review aims to explore and understand factors that affect dermatophyte infection with an emphasis on the prevalence, clinical signs, pathogenesis, immune response, and the roles of cortisol and cytokines in companion animals infected by a dermatophyte.
... On days 0, 7, 14, 21, and 28 of the experiment, we subjected members of each group to clinical scoring according to the data presented in Table 1, following which their photographs were taken [14]. On day 29 of the experiment, we stopped treatment, the animals were euthanized under general anesthesia, and skin samples were acquired using the punch biopsy method. ...
... The improvements observed on days 0, 7, 14, 21, and 28 are summarized in Table 2. Improvement findings categorized according to days are given in Table 3. Considering these outcomes, we noted that the most significant improvement was observed in Group C, Table 1. Clinical scoring parameters [14]. followed by Group A, Group D, and Group B. The most significant degree of improvement by day 28 was observed in Group C and the least in Group E (Figure 1). ...
... Slim and Karelson [17] highlighted the fact that oral and topical terbinafine treatment could be used to treat children infected with M. canis; however, the side effects include vomiting, pruritus, and local erythema. Studies associated with the treatment of M. canis infections with terbinafine have reported successful outcomes in both human and animal cases [14,18]. Here, we applied a terbinafine topical cream as a positive control group and compared its efficacy to alternative treatment modalities. ...
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This study aimed to investigate the treatment outcomes of topical application of boric acid, boron-doped gel, and ozonated olive oil in cases of Microsporum canis-induced dermatophytosis. Furthermore, the outcomes were compared to those of terbinafine administration. We included 39 female Wistar albino rats weighing 200–250 g and created an M. canis-infected area on the skin of their backs. The rats were clinically scored on days 0, 7, 14, 21, and 28 and underwent histopathological evaluation. All the treated groups demonstrated significantly lower clinical scores than the control group (P < 0.05). Fewer inflammation cells were observed in the samples of groups treated with 3% boric acid and sodium pentaborate pentahydrate gel than in those of the control group. According to the histopathological evaluation, the groups treated with 3% boric acid and sodium pentaborate pentahydrate gel were statistically different from the control and other treatment groups (P < 0.05). Our results indicated that treatment with 3% boric acid and sodium pentaborate gel was adequate in resolving M. canis-induced infection in rats. Therefore, gels containing 3% boric acid and sodium pentaborate pentahydrate may be alternatives to antifungal agents such as terbinafine by ensuring easy, reliable, inexpensive, and effective treatment modalities.
... Fungal diseases can affect the oral mucosa, skin, nails, hair, lungs, brain, or several organs and tissues simultaneously [6,18,19,24,25,35]. Constant global changes and the (B-F)-representative images of compounds 1, 3, 5, 11, and 12, respectively; the black arrows point to a live larva in its characteristic shape (sinusoidal) and the orange arrow shows a dead larva in its characteristic rod shape. ...
... Fungal diseases can affect the oral mucosa, skin, nails, hair, lungs, brain, or several organs and tissues simultaneously [6,18,19,24,25,35]. Constant global changes and the advent of new pandemics and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, and dimorphic fungi such as H. capsulatum and P. brasiliensis [1,2,26]. ...
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Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.
... Dermatophytosis is a common self-limiting zoonotic fungal disease which caused by infection of certain types of dermatophyte [1,2] that fungi of 3 fundamental genera specifically, Microsporum, Trichophyton and epidermophyton. We will not wait its self-limiting cause it Causes economic losses. ...
... The results of different investigations recognized that main species causing dermatophytosis in small animals is microsporum-canis in 81.8 %to 97% of total cases [1,2,6]. ...
... Dermatophytes are filamentous fungi that may infect keratinized structures such as the skin, hair, and nails of humans and animals, causing dermatophytosis (Costa-Orlandi et al., 2014;Heidrich et al., 2015;Maraki and Mavromanolaki, 2016). This disease is globally considered as the most common dermatological zoonosis, with a prevalence of 20-25% in the global human population (Ivaskiene et al., 2016). ...
... Nevertheless, the principal genera include Trichophyton, Microsporum, and Epidermophyton (Moriello, 2004;Costa-Orlandi et al., 2014;Maraki and Mavromanolaki, 2016;De Hoog et al., 2017). Dermatophytes can be grouped as anthropophilic, zoophilic, and geophilic (Moriello, 2004;Ivaskiene et al., 2016). T. rubrum is the most prevalent dermatophyte species, accounting for more than 80% of all infections. ...
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Dermatophytes, fungi that cause dermatophytosis, can invade keratinized tissues in humans and animals. The biofilm-forming ability of these fungi was described recently, and it may be correlated with the long treatment period and common recurrences of this mycosis. In this study, we evaluated the anti-dermatophytic and anti-biofilm activity of 2-hydroxychalcone (2-chalcone) in the dark and photodynamic therapy (PDT)-mediated and to determine its mechanism of action. Trichophyton rubrum and Trichophyton mentagrophytes strains were used in the study. The antifungal susceptibility test of planktonic cells, early-stage biofilms, and mature biofilms were performed using colorimetric methods. Topographies were visualized by scanning electron microscopy (SEM). Human skin keratinocyte (HaCat) monolayers were also used in the cytotoxicity assays. The mechanisms of action of 2-chalcone in the dark and under photoexcitation were investigated using confocal microscopy and the quantification of ergosterol, reactive oxygen species (ROS), and death induction by apoptosis/necrosis. All strains, in the planktonic form, were inhibited after treatment with 2-chalcone (minimum inhibitory concentration (MIC) = 7.8-15.6 mg/L), terbinafine (TRB) (MIC = 0.008–0.03 mg/L), and fluconazole (FLZ) (1–512 mg/L). Early-stage biofilm and mature biofilms were inhibited by 2-chalcone at concentrations of 15.6 mg/L and 31.2 mg/L in all tested strains. However, mature biofilms were resistant to all the antifungal drugs tested. When planktonic cells and biofilms (early-stage and mature) were treated with 2-chalcone-mediated PDT, the inhibitory concentrations were reduced by four times (2–7.8 mg/L). SEM images of biofilms treated with 2-chalcone showed cell wall collapse, resulting from a probable extravasation of cytoplasmic content. The toxicity of 2-chalcone in HaCat cells showed higher IC 50 values in the dark than under photoexcitation. Further, 2-chalcone targets ergosterol in the cell and promotes the generation of ROS, resulting in cell death by apoptosis and necrosis. Overall, 2-chalcone-mediated PDT is a promising and safe drug candidate against dermatophytes, particularly in anti-biofilm treatment.
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OVERVIEW: Dermatophytosis, usually caused by Microsporum canis, is the most common fungal infection in cats worldwide, and one of the most important infectious skin diseases in this species. Many adult cats are asymptomatic carriers. Severe clinical signs are seen mostly in kittens or immunosuppressed adults. Poor hygiene is a predisposing factor, and the disease may be endemic in shelters or catteries. Humans may be easily infected and develop a similar skin disease. INFECTION: Infectious arthrospores produced by dermatophytes may survive in the environment for about a year. They are transmitted through contact with sick cats or healthy carriers, but also on dust particles, brushes, clothes and other fomites. DISEASE SIGNS: Circular alopecia, desquamation and sometimes an erythematous margin around central healing ('ringworm') are typical. In many cats this is a self-limiting disease with hair loss and scaling only. In immunosuppressed animals, the outcome may be a multifocal or generalised skin disease. DIAGNOSIS: Wood's lamp examination and microscopic detection of arthrospores on hairs are simple methods to confirm M canis infection, but their sensitivity is relatively low. The gold standard for detection is culture on Sabouraud agar of hairs and scales collected from new lesions. DISEASE MANAGEMENT: In shelters and catteries eradication is difficult. Essential is a combination of systemic and topical treatments, maintained for several weeks. For systemic therapy itraconazole is the drug of choice, terbinafine an alternative. Recommended topical treatment is repeated body rinse with an enilconazole solution or miconazole with or without chlorhexidine. In catteries/shelters medication must be accompanied by intensive decontamination of the environment. VACCINATION: Few efficacy studies on anti-M canis vaccines (prophylactic or therapeutic) for cats have been published, and a safe and efficient vaccine is not available.
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T. Kotnik, M. âerne: Clinical and Histopathological Evaluation of Terbinafine Treatment in Cats Experimentally Infected with Microsporum canis. Acta Vet. Brno 2006, 75: 541-547. The efficacy of terbinafine hydrochloride (Lamisil ® , Novartis) in the treatment of 27 M. canis- infected cats was followed. Treatment was started on the 17 th day post inoculation (p.i.), when successful experimental infection was proved. Nine cats were treated with low-dose terbinafine 10- 20 mg/kg QD (LD group), nine cats were treated with high-dose terbinafine 30- 40 mg/kg QD (HD group) and nine were left untreated as a control group (C group). The efficacy of the treatment was evaluated using Wood's lamp examination, fungal culture and histopathology. All cats were positive 14 days p.i. Sixty days p.i. 8 cats from the LD group, 9 from the C group and 2 cats from the HD group had fungi in the tissue. Ninety days p.i. the HD group was free of fungi in the skin and other tests became negative on the 120 th day p.i. Statistically significant differences were found between the HD group and both of the other groups (p < 0.005) on 60th and the 90th day p.i. Experimental infection with M. canis yielded an inflammatory reaction of a mononuclear and neutrophil type in the cat skin. Hyperplastic interstitial dermatitis was a predominant tissue reaction although other types were also present during the study. Dermatophytes, small animals, antifungals, histopathology
Dermatophytosis remains one of the most frequent infectious diseases in veterinary dermatology and clinical investigations are still required to better understand the epidemiology of the disease and provide new treatment options. Since dermatophytosis is highly contagious and zoonotic, its treatment must be effective, safe, comfortable to administer and inexpensive. Topical drug delivery formulations become more widespread in veterinary medicine. Topical therapy is often preferred to oral drug administration in the treatment of cutaneous fungal infections in pets. The aim of this study was to evaluate the efficacy of novel topical formulations in the treatment of dermatophytosis in guinea pigs. The clinical efficacy and safety of once daily topical administration of E-1 cream and T-1 cream was assessed in experimental tinea corporis in guinea pigs and compared with licensed antifungal topical preparation Imaverol, as well as the vehicle of the creams. The clinical features improvement after 1% terbinafine hydrochloride cream application varied from 41.25% (day 12) to 100% (day 36), after 1% econazole nitrate cream resorting - from 22.5% (day 12) to 100% (day 44). Clinical effectiveness of Imaverol solution varied from 16.25% (day 12) to 100% (day 48). When animals were treated with vehicle of the creams, mean percentage improvement of clinical features varied from 20% (day 12) to 100% (day 48). The experimentally infected untreated guinea pigs in control group showed spontaneous resolution of lesions within 56 days.
The aim of this review is to discuss the critical points of current knowledge about pathogenic fungi cell structure, function and susceptible targets for antifungal agents. Unlike bacteria, both fungi and mammalian are eukaryotic cells. Thus, fungal and mammalian cells are comparable at the molecular level and protein synthesis function. However, the antifungal agents develop a toxic effect on mammalian cells. The main difference between fungal and mammalian cells is that animal cells do not have a cell wall, they are enclosed by a plasma membrane, and fungal cell has a cell wall, which is an obvious target for antifungal agents. Cellular differences between fungal and mammalian cells gave the opportunity to modify well-known or design new antifungal agents, that would kill off the fungal organism without dangerous effects on the host. The identification of new susceptible targets in fungal cell lead to development of effective and less toxic to the host antifungals. The fungal cell wall is a dynamic organelle that must provide the cell with sufficient mechanical strength. Fungal cell wall is structurally unique, is comprised of glycoproteins and polysaccharides, mainly glucan and chitin, which are cross-linked together to form a complex network, which forms the structural basis of the cell wall. Ergosterol is an essential component of the fungal cell membrane, required to maintain cellular rigidity and integrity. Ergosterol biosynthesis pathway is a specific branch of the mevalonate pathway and is fungal-specific and unique, there are several enzymatic steps that are attractive targets for antifungal drugs. Azoles, allilamines, thiocarbamates and morpholines inhibit the synthesis of ergosterol. Since the (1,3)-beta-glucan structure is not found in mammalian cells, enzyme (1,3)-beta-glucan synthase has become a target for echinocandins and pneumocandins. The search for new antifungal drugs and strategies, that will focus on inhibition of ergosterol, glucan, chitin synthesis and more targets, continues. Antifungal agents, their mode of action and application will be reviewed in the next edition.
Practical drug development approaches presented by leading experts. Designed to support the development of new, effective therapeutics, Topical and Transdermal Drug Delivery: Principles and Practice explains the principles underlying the field and then demonstrates how these principles are put into practice in the design and development of new drug products. Drawing together and reviewing the latest research findings, the book focuses on practical, tested, and proven approaches that are backed by industry case studies and the authors' firsthand experience. Moreover, the book emphasizes the mechanistic information that is essential for successful drug product development. Topical and Transdermal Drug Delivery: Principles and Practice is divided into two parts: Part One, Current Science, Skin Permeation, and Enhancement Approaches, offers readers a fundamental understanding of the underlying science in the field. It describes the principles and techniques needed to successfully perform experimental approaches, covering such issues as skin permeation, enhancement, and assessment. Part Two, Topical and Transdermal Product Development, guides readers through the complete product development process from concept to approval, offering practical tips and cautions from experts in the field. This part also discusses regulations that are specific to the development of dermal drug products. The final chapter explores current and future trends, forecasting new development techniques and therapeutics. •Throughout the book, the authors clearly set forth the basic science and experimental procedures, making it possible for researchers to design their own experimental approaches and accurately interpret their results. •With contributions from experienced drug researchers, this text is highly recommended for all researchers involved in topical and transdermal product development who need to know both the state of the science and the standards of practice.
The incidence of fungal infections have tendency to increase worldwide. The need for new antifungal agents has arisen largely through the increase in numbers of fungal infections. Relatively few agents were available for treatment of mycoses, e.g. amphotericin B, flucytosine, griseofulvine and few azoles (ketoconazole, enilconazole). The knowledge of fungal cell structure, function and metabolism gave the opportunity to synthesize new agents. The search for new, potent and broadly active antimycotics, new targets in fungal cell, modification of currently known agents was of a big interest during the past decades. This lead to development of novel antifungals belonging to wide range of structural classes, selectively acting on novel targets with fewer side effects to animals. Recently, there are more than one hundred antimycotic agents that possess fungicidal or fungistatic activity. Modern antimycotics are active chemical compounds, missaplication of which may be harmful to an animal. In our previous review the fungal cell structure, function and targets for antifungal agents were described. This review includes the mechanism of action, spectra of activity, administration of antifungals in current use in veterinary medicine, efficacy or toxicity of antifungal therapy.
The pharmacokinetics of terbinafine was studied in six healthy fasted cats following a single intravenous and oral administration at a dose of 10 mg/kg and 30 mg/kg, respectively, according to a two-period crossover design. Plasma terbinafine concentrations were determined using a reverse phase liquid chromatographic method. The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the terminal half-life and area under the curve from time 0 to infinity were 10.40 ± 4.56 h, 15.20 ± 3.61 h·µg/ml, respectively. After oral dosing, the mean maximum concentration was 3.22 ± 0.60 µg/ml, reached at 1.33 ± 0.41 h. The terminal half-life, area under the curve from time 0 to infinity and apparent volume of distribution were 8.01 ± 3.46 h, 13.77 ± 4.99 h·µg/ml, 25.63 ± 6.29 l/kg, respectively. The absolute bioavailability of terbinafine hydrochloride tablets after oral administration was 31.00 ± 10.85%. Although bioavailability was low, excellent penetration at the site of infection and low minimum inhibitory concentrations values provided terbinafine with good efficacy against dermatophyte infections.