Treatment of Microsporum canis inf ected cats with terbinafine 
Original experimental study 
TREATMENT OF MICROSPORUM CANIS 
INFECTED CATS WITH TERBINAFINE 
E. Orožim 
ABSTRACT 
Terbinafine is a new allylamine antifungal agent with its primary characteristic of fungicida! action. Because 
of its excellent qualities this drug is interesting for use in veterinary medicine too. Among the diseases, which 
are common in humans and animals, we are dealing with the effective control of Microsporum canis infection. 
Humans are often infected by contact with cats. The most dangerous sources of infection are stray cats and 
asymptomatic carriers. Because an effective vaccine against the disease is stili not available, it is important 
to detect infected cats and treat them. Due to excellent results in humans it is reasonable to use the 
terbinafine. 
Our preliminary results using terbinafine in cats showed that cats tolerated terbinafine well in a dosage 
of 10-20 mg/kg daily for 5 months. Half of the cats got cured in 145 days, and ali were cured in 159 days. 
It is too early to estimate the result of such treatment, but according to our clinical experience with the 
combination of drugs, we would expect shorter treatment periods from a fungicida! agent. It is highly probable 
that the dose 10-20 mg/kg in cats acts fungistatically and that higher doses should also be tri ed. 
KEY WORDS 
terbinafine, cats, M.canis, dermatophytes, treatment 
INTRODUCTION 
Microsporum canis (M. canis) infection in man was 
first recognized in Slovenia in 1977 (1) and in 
animals in 1984 (2). From 1986 we have been able 
to follow a constant increase in the number of cases 
and the spread of the disease ali over the country 
(3). Important sources of infection for humans are 
considered household or stray cats ( 4 ). M.canis is 
acta dermatovenerologica A.P.A. Vol 7, 98, No 3-4 
the most common cause of dermatophytosis in cats 
(5). It is estimated that seventy percent of humans 
become infected by contact with cats (1), and half 
of exposed individuals become infected (6). Besides 
the direct infection from animals, hair shafts containing 
infectious arthrospores may remain infectious in the 
environment up to 18 months (7,8). Asymptomatic 
carriers of M.canis in cats represent a very important 
157 
Treatment of Microsporum canis infected cats with terbinafine 
Figure l. Positive Wood's lamp examination of the 
experimentally infected site. A well-expressed lesion is 
presented. We were able to observe the fluorescence of 
the hair shafts as soon as 7 days post inoculation. 
and often unsuspected threat to animals and humans. 
Show cats, cattery cats, and those frequenting veterinary 
clinics, in 6.5 to 100 per cent may be asymptomatic 
carriers of M canis (9). Approximately one half of 
infected cats may not show any clinical signs (2,4). 
The isolation of M. canis from a cat should be 
considered as a significant finding and treatment 
should be initiated (10). 
Terbinafine is a new allylamine antifungal agent, 
which acts by preventing fungal ergosterol biosynthesis 
via specific and selective inhibition of fungal squalene 
epoxidase. Fungi treated with these drugs accumulate 
squalene while becoming deficient in ergosterol, an 
essential component of fungal celi membranes. It 
seems that the terbinafine's fungicida! action is 
o 
Figure 2. lnfected hair at the high power magnification, 
400 x, native. Changed, thick hair shaft (1) surrounded 
by arthrospores (2), and numerous of hyphae (3). 
158 
-
Figure 3. lnfected hair; periodic acid Schiff (PAS) 
stain, 400 x. A changed hair shaft (1), pink arthrospores 
surrounding the involved hair (2) and wall of the hair 
follicle seems to be normal (3). 
Figure 4. lnfected site of a cat, day 19. 
acta dermatovenerologica A.P.A. Vol 7, 98, No 3-4 
Treatment of Microspontm canis infected cats with terbinafine 
closely associated with the development of high 
intracellular squalene concentrations (11,12,13). The 
development of high intracellular squalene concen-
trations is not characteristic of azoles - another 
large group of antifungal drugs. These drugs prevent 
synthesis of ergosterol at a different step, by inhibition 
of the enzyme 14-cx-demethylase. The mode of their 
action is fungistatic and they exhibit side effects by 
affecting sterol synthesis in mammals (11,13,14). 
Terbinafine is active in vitro against a wide range 
of pathogenic fungi and is exceptionally potent 
against dermatophytes (12,15,16). The clinical expe-
rience with terbinafine in humans is extensive: an 
estimated 5 million patients have already been treated 
with oral terbinafine (17). There have been no 
reports to date on acquired resistance to th(: drug. 
This may also be connected with its fungicida! 
action, which leaves no opportunity for resistance to 
develop (18,19). The drug may provoke minor side 
effects in humans, mostly gastrointestinal disturbances, 
which appear at the beginning of the treatment and 
are transient (20,21). Because of its excellent qualities 
this drug is interesting for use in veterinary medicine 
too. According to our knowledge there are no 
published data yet on clinical use of terbinafine in 
cats. 
MATERIAL AND METHODS 
ANIMALS 
Six healthy cats of domestic breed, five females, 
and one male were included in the study. The age 
at the beginning of the study ranged between 3 -
4,5 months. Before entering the study they were 
kept inside the facilities of the Veterinary faculty of 
Ljubljana. They never became exposed to any 
pathogenic fungi. They were FIV (Feline immuno-
deficiency virus) and FeL V (Feline leukemia virus) 
negative and received antihelmintics twice. Complete 
Table l. The scheme of the dosage of terbinafine. It is 
designed in the manner that the dose per kg ranged 
always between 1 O to 20 mg, considering the growth of 
the young cats. 
0,0 - 3,0 kg 
3,1 - 6,0 kg 
6,1-9,0kg 
1/4 
1/2 
3/4 
acta de,matovenerologica A.P.A. Vol 7, 98, No 3-4 
blood count, fungal culture and enzyme tests (AP, 
AST, ALT, GLDH, LDH) were performed before 
the study. During the study they were housed 
separately in individual cages. 
PREPARATION OF CONTAGIOUS MATERIAL 
The cats were experimentally infected with a Mcanis 
isolate of feline origin (1032/97) obtained from a 
hair sample of a naturally infected cat at the Small 
animal clinic of the Veterinary faculty of Ljubljana. 
The strain was highly fluorescent under the Wood's 
lamp. We prepared the contagious material using a 
similar method as it is described in literature (22). 
The hair sample was cultured for 14 days on 
Sabouraud's dextrose agar. Two plates were poured 
with 10 ml of sterile water each and the mycelial 
growth was gently scraped off. We used this suspension 
in the next 3 consecutive days. During the infection 
procedure, the suspension was stored at 4°C. 
INDUCTION OF INFECTION 
Cats were sedated with medetomidine (DomitorR, 
Orion corp. Farmos, Finland) 0,1 ml/kg i/m and 
placed in dextral laterni recumbency. The hair was 
clipped from the left caudo-lateral thorax of each 
cat using AesculapR clippers so that 1-2 mm long 
hair remained spared in the clipped area. A 5 x 4 
cm area was marked with a water-resistant pencil. 
The skin was gently scarified with a scalpel hlade 
and 1 ml of mycelial suspension was rubbed into 
the c!ipped area using a sterile cotton swab. The 
same procedure was repeated for the next two 
consecutive days but without scarification; instead 
we gently rubbed the suspension into the skin for at 
least 3 minutes each tirne. The animals were fitted 
with Elisabethan collars for the incubation period of 
14 days, because licking might remove the fungi 
from the skin and render the infection procedure 
more difficult (7,23). 
TREATMENT AND MONITORING 
During the incubation period of 14 days cats wore 
Elisabethan collars so they couldn't lick the infected 
area. We monitored daily their general condition as 
well as the infected site and fluorescence with 
Wood's lamp (Figure 1). On days 4, 7, and 14 we 
sedated the animals again and took 6 mm punch 
skin biopsies, on days 7 and 14 we obtained b1ood 
and hairs from the infected cats. 
The infection was confirmed on day 14 by culture, 
159 
Treatrnent of Microsporurn canis infected cats with terbinafine 
microscopy, and histology. 
On day 17 we started treatment with terbinafine 
(LamisilR, Novartis) 125 mg tablets (Table 1). The 
portions of a tablet as presented in Table 1 were 
placed individually into the mouth of each animal 
to make sure that every cat took the medicament. 
During treatment we daily monitored the general 
health status in order to recognize any side effects. 
Every week far the first 3 months and every 2nd 
week far the consecutive 2 months we estimated 
the clinical features and took body weight. We 
adjusted the dose of the medicament weekly when 
necessary. Hair samples were obtained every 2 weeks 
and stored far microscopy and fungal culture. Blood 
samples were obtained at the beginning of treatment 
and at week 10 of treatment. Skin biopsies were 
obtained at weeks 12, 14, 16, 20, and 24. 
RESULTS 
EXPERIMENT AL INFECTION 
Experimental infection was successful in ali 6 cats, 
as confirmed by culture, microscopy and histology 
at day 14 post inoculation (Figures 2 and 3). 
SIDE EFFECTS 
At the beginning of treatment (8th day) we noticed 
a softer stool in 4 animals. This was transient, and 
otherwise the animals were well. This appeared 
again a few times during treatment. One cat also 
vomited after taking a tablet on day 52. We then 
gave to give the tablets simultaneously with faod 
and the sign disappearecl. The same cat also developed 
Table 2. Days of treatment with terbinafine in cats 
with experimental M.canis infection (No=6). 
159 o 
160 
lymphadenitis after the biopsy. We treated it far 9 
clays with amoxiclave injections ancl it responclecl to 
the treatment. Ali 6 animals completed the study. 
DRUG DOSAGE 
The animals hacl no problems with taking the 
medication. Adjustment of the close was only necessary 
in one cat during treatment because of exceeded 
weight limit. At the beginning of treatment the 
dosage per kg ranged from 12.76 mg to 20.8 mg/kg, 
median 17 .05 mg/kg. The doses at the ene! of the 
treatment ranged from 10.96 mg to 16.89 mg/kg, 
median 13.37 mg/kg ( data not shown). 
THE TIME OF CURE 
Far the estimation of the cure rate we considered 
the presence of alopecia, the presence of the Woocl's 
lamp fluorescence, microscopy results, biopsy results 
ancl fungal culture results. Any animal which hacl 2 
or more positive tests was considered not cured. 
Table 2 shows the numbers of healed animals with 
the clays until cure. 
DISCUSSION 
Experimental infection was successful in ali animals, 
we consider the methocl used as good ancl reliable . 
Periodically, a soft stool was noticed cluring treatment. 
This might be a side effect triggered by the drug. 
In humans mile! gastrointestinal clisturbances are 
one of the most common side effects with an 
incidence of 5%, while the inciclence of ali other 
side effects (skin rashes, loss of taste, nervous 
symptoms, heaclaches and elevated !iver enzymes) 
accounts far 5.4% (21). Because the clisturbance 
was mile! ancl transient, we didn ' t consider it 
particularly important. Vomiting in one cat might 
show her special susceptibility to the drug or it may 
be only have been its reflex to bacl taste. The 
problem was resolved with simultaneous feecling. 
Recently, a stucly of pharmakokinetics of terbinafine 
in cats was done in Vienna (24). The author suggested 
a dose of 10 mg per kg daily to be the most 
appropriate. When we clevelopecl the treatment 
schedule, we tried to use this dose as much as 
possible. Among the tests far detection of the 
fungal skin infection the fungal culture is considered 
the most reliable (10), but it may also reflect a 
recent exposure to a contaminated environment (9). 
We fallowed the animals until fungal cultures were 
acta derrnatovenerologica A.P.A. Vol 7, 98, No 3-4 
Treatment of Microsporum canis infected cats with terbinafine 
negative. Because cats were caged for a long period 
we felt that the possibility of false positive culture 
results was greater. For that reason we decided to 
consider those animals not cured with at least 2 
positive diagnostic tests at the same tirne. The 
sensitivity of microscopic examination was estimated 
at 70% and sensitivity of histology is around 80%, 
but when any of the tests is positive, it means 
definitive proof of infection (9). According to this 
we found that within 70 days of treatment no cat 
was healed, within 145 days of treatment one half 
of animals were cured and ali were cured within 
159 days. 
It is too early to comment these preliminary 
results because it is necessary to wait for the data 
of the controls and the higher dosage groups. The 
occurrance of spontaneous remission must also be 
considered. In shorthaired cats it may occur within 
4 months (9) . We also have clinical experience with 
terbinafine used together with topically administered 
enilconazole in naturally M.canis infected cats. During 
the years 1995 and 1996 we used terbinafine orally 
in 18 cats, confirmed to be M.canis infected or 
carriers. Additionally to terbinafine, animals received 
enilconazol baths twice a week. Although the dosage 
of terbinafine ranged from 13.2 to 41.7 mg per kg 
daily, cats perfectly tolerated (both) drugs. Only one 
cat vomited. The dose used in this cat was 19.5 mg 
per kg daily. The tirne of cure ranged from 18 to 
60 days with an average of 38.8 days (Orožim, 
unpublished data). We don't know what part either 
drug played in the treatment, but azoles and 
terbinafine may act synergistically for two reasons: 
they both disturb the synthesis of ergosterol on two 
different consecutive steps. Second: hepatic cytochrome 
P-450 is the crucial enzyme system in terbinafine 
degradation (13). As we know, azoles strongly inhibit 
this group of enzymes (11,13,14). 
CONCLUSIONS 
Our preliminary results show that cats tolerated 
terbinafine well in dosage of 10-20 mg/kg daily for 
5 months. Half of the cats were cured in 145 days, 
and ali were cured in 159 days. It is too early to 
estimate the result of such treatment, but according 
to our clinical experience with the combination of 
drugs we would expect shorter treatment periods 
from the fungicida! agent. It is highly possible that 
the dose of 10-20 mg/kg in cats only acts fungistatically 
and that higher doses should also be tried. 
ACKNOWLEDGEMENT 
We thank Novartis phanna for their kind support of this study. 
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AUTOR'S ADDRESS 
E . Orožim, DVM, MSc, Small animal clinic, Veterinary faculty of Ljubljana, Gerbičeva 60, 
1000 Ljubljana, Slovenia 
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