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VDE_274.

fm Page 347 Thursday, November 15, 2001 7:22 PM

Veterinary Dermatology 2001, 12, 347 350

sBlackwell Science Ltd

Efficacy of itraconazole as a combined continuous/pulse


therapy in feline dermatophytosis: preliminary results
in nine cases
S. COLOMBO*, L. CORNEGLIANI and A. VERCELLI
*Istituto di Patologia Speciale e Clinica Medica Veterinaria Facolta di Medicina Veterinaria, Universita degli
Studi di Milano, Via Celoria 10, I-20100 Milan, Italy Ambulatorio Veterinario Associato, Corso Traiano
99/D, I-10135 Torino, Italy
(Received 8 March 2001; accepted 28 June 2001)

Abstract This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline
dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole
at 10 mg kg1 orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the
same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary.
Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after
56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at
day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment
of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.

Keywords: cat, dermatophytosis, itraconazole, pulse therapy.

INTRODUCTION
Feline dermatophytosis is a fungal infection affecting
keratinized tissues, most commonly caused by Microsporum canis. In healthy cats it is a self-limiting disease,
but it is a zoonosis and 50% of people exposed to
affected cats or asymptomatic carriers become
infected.1
Systemic therapy is the treatment of choice in feline
dermatophytosis, and griseofulvin at 50 mg kg1 orally
once daily is still considered the drug of choice for its
efficacy and low cost.1,2 However, side effects may be common and potentially severe in cats, particularly in longhaired breeds and FIV-positive animals.1 If griseofulvin
is not successful or adverse effects are observed, itraconazole may represent an alternative optional treatment.3
Itraconazole (Sporanox, Janssen) is a triazole derivative of the azole group of drugs. It acts by altering
fungal cell membrane permeability through inhibition
of ergosterol synthesis.4,5 Itraconazole at 10 mg kg1
orally once daily has been used successfully and safely
to treat dermatophytosis in experimentally infected
cats.3 In human medicine, itraconazole has been demonstrated to persist in the stratum corneum for 3
4 weeks after discontinuation of therapy,6 and has been
widely used as a pulse therapy for dermatophytosis in
both adults and children.710
Correspondence: Silvia Colombo, University of Edinburgh, The
Royal (Dick) School of Veterinary Studies, Department of Veterinary
Clinical Studies, Hospital for Small Animals, Easter Bush Veterinary
Centre, Roslin, Midlothian EH25 9RG, UK. Tel.: +44 131 650 7650;
Fax: +44 131 650 7652; E-mail: silvia.colombo@ed.ac.uk
2001 Blackwell Science Ltd

The main limitation to the use of itraconazole in


veterinary medicine is cost, and pulse therapy is a less
expensive option than continuous therapy. The purpose of this study was to evaluate the efficacy of itraconazole as a combined continuous and pulse therapy in
feline dermatophytosis.

MATERIALS AND METHODS


Nine privately owned cats were included in the study.
Six cats were Domestic Short Hairs and three were Persians. Ages ranged between 2 months and 7 years, with
a mean age of 20.5 months. Seven cats were males (five
entire and two castrated) and two were females (one
entire and one spayed). Duration of clinical signs varied
between 2 weeks and 1 year in seven cats and was
unknown for two stray kittens, which had been recently
adopted (Table 1).
Dermatophytosis was diagnosed in all cats by suggestive clinical features, detection of microconidia by
microscopic examination of hair samples and positive
fungal cultures. Seven cats presented with alopecia,
erythema, scaling and crusting with variable distribution, one cat had miliary dermatitis and one cat showed
both clinical presentations. Pruritus was observed in
two cases. Samples for fungal culture were inoculated
on both Sabourauds dextrose agar and dermatophyte
test medium (DTM) and incubated at 27 C and 30%
humidity. The cultures were checked daily for up to
21 days. Dermatophyte identification was performed
by macroscopic features of the colonies, colour change
of the medium (DTM) and microscopic examination of
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S. Colombo et al.

Case
no.

Breed

Age

Sex

Duration
of lesions

Time to
mycological
cure (days)

1
2
3
4
5
6
7
8
9

Persian
Domestic Short Hair
Domestic Short Hair
Persian
Domestic Short Hair
Domestic Short Hair
Domestic Short Hair
Domestic Short Hair
Persian

4 months
1 year
7 years
2 years
2 months
2 years
2 months
3 months
2.5 years

M
NM
NM
F
M
SF
M
M
M

2 months
1 month
1.5 months
1 year
Unknown
4 months
Unknown
2 weeks
3 months

70
56
56
56
56
56
56
56
56

Table 1. Case details of nine cats with


dermatophytosis which received combined
continuous and pulse therapy with
itraconazole

F, female; M, male; NM, castrated male; SF, spayed female.

samples obtained from the colonies grown on Sabourauds


dextrose agar and stained with lactophenol cotton
blue.1 Microsporum canis was isolated in all cases.
All cats were treated orally with itraconazole at
10 mg kg1 once daily with food for 28 consecutive
days. Itraconazole capsules were reformulated for each
cat. At the end of this period, treatment was continued
with itraconazole at 10 mg kg1 once daily on alternate
weeks (1 week off, 1 week on). Physical examinations
and fungal cultures (Mackenzie brush technique) were
performed every 2 weeks starting on day 28, until
mycological cure was achieved. Mycological cure was
defined as obtaining two consecutive negative cultures
at 2-week intervals. The alternate week treatment was
continued for all cats until the result of the second
negative culture was received (2 weeks after the sample
was taken). Hair coat clipping and topical therapy
were not performed. Owners were advised to reduce
contact with affected cats and to treat the environment by aggressive cleaning with undiluted sodium
hypochlorite (as household bleach) where possible.

RESULTS
Eight cats achieved two consecutive negative cultures
on day 28 and day 42. These cats were considered
cured after 56 days, because treatment was continued
while waiting for the results of the fungal cultures. No
adverse effects were observed.
One cat was still culture positive on day 28, but
achieved two consecutive negative cultures on day 42
and day 56. This cat was considered cured in 70 days,
and no adverse effects were observed (Table 1).

DISCUSSION
From the results obtained with this study, itraconazole
as a combined continuous and pulse therapy seems to
be an effective treatment for feline dermatophytosis.
The time needed to obtain mycological cure is comparable with other protocols.3
Eight of nine cats in this study were considered cured
after 56 days. In fact, these cats may have been cured
earlier, as they were culture negative on samples taken
2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 347 350

on days 28 and 42. However, it was decided to continue


treatment until the results of the second fungal culture
were received due to the zoonotic potential of the disease. Moreover, it has been shown that infected cats
may have positive culture results for several weeks after
the resolution of the clinical signs.2,3,11
Dermatophytosis is a self-limiting disease in
immune-competent cats, and the immune response
is thought to be both humoral and cell mediated.12
Experimental studies have shown that infected shorthaired cats recover spontaneously and become culture
negative within 3 months.12,13 When evaluating the efficacy of a treatment for dermatophytosis, the possibility
of self-cure needs to be considered. In this study, it was
not possible to use untreated animals as a control
group as the study was performed in practice with privately owned cats. Thus, the results must be considered
preliminary and should be confirmed by a controlled
study with a group of untreated cats. However, if the
experimental studies reflected the clinical situation, the
combined continuous and pulse therapy with itraconazole appeared to shorten the duration of infection by
approximately half (42 days vs. 90). Furthermore, the
experimental studies of dermatophytosis used exclusively short-haired cats.12,13 Long-haired cats can
undergo spontaneous resolution, but it may take 1.5
4 years.1 In our study, three Persian cats were treated.
Two of the three were considered cured in 56 days, and
the third recovered in 70 days.
In human medicine, itraconazole has been proven to
persist in keratinized tissues for 34 weeks after the
last oral dose,6 and various studies have evaluated its
efficacy as a pulse therapy for onychomycosis and for
tinea capitis in children.710 The only published study
on the pharmacokinetics of itraconazole in cats
showed that plasma steady-state concentrations may
take up to 3 weeks to become established.14 However,
the drug concentration and persistence in keratinized
tissues were not evaluated. A dose of 10 mg kg1 with
a 24-h dosing interval should be appropriate.14 Adverse
effects of itraconazole in cats are uncommon and
include anorexia, weight loss, increased serum alanine
aminotransferase concentrations and teratogenicity.5
No adverse effects were observed in this study.
Currently, the recommended treatment for feline dermatophytosis involves environmental decontamination

VDE_274.fm Page 349 Thursday, November 15, 2001 7:22 PM

Itraconazole in feline dermatophytosis


and topical therapy, as well as systemic therapy.1,2
Environmental decontamination is strongly recommended, as arthrospores may survive for up to
18 months.15 Hair coat clipping is usually recommended in severe cases and in long-haired cats only,
but one study has shown that clinical lesions may
worsen within 710 days after clipping.2 Topical therapy has been described as a useful adjunctive treatment
to kill spores on the hair coat and to reduce environmental contamination, but it cannot be recommended
as sole therapy.11,16 Hair coat clipping and topical
treatment were not performed in this study in order to
evaluate the efficacy of itraconazole as a sole treatment
for feline dermatophytosis.
Pulse therapy is more cost-effective than continuous
therapy. As itraconazole is an expensive drug, it would
be interesting to assess its efficacy as a pulse therapy
from the beginning of treatment and at less frequent
intervals. If itraconazole was effective as pulse therapy,
it may be as cheap to use as griseofulvin. However,
pharmacokinetic studies are needed to evaluate itraconazole concentrations and persistence in feline keratinized tissues. The efficacy of itraconazole as a pulse
therapy should also be evaluated in cats of different
breeds and, particularly, in Persian cats.

ACKNOWLEDGEMENTS
The authors are grateful to the Ambulatorio Veterinario Associato Dr F. Canepa Dr L. Portigliotti
(Novara, Italy), Clinica Veterinaria Citta' di Monza
(Monza, Italy) and to the Ambulatorio Veterinario Dr
E. Jommi (Milano, Italy) for referring the cases. The
authors are also very grateful to Drs P. B. Hill and
K. L. Thoday for their advice and comments on this
paper.

REFERENCES
1. Scott, D.W., Miller, W.H., Griffin, C.E. Muller and Kirks
Small Animal Dermatology, 6th edn. Philadelphia: W.B.
Saunders, 2001: 336.
2. Moriello, K.A., DeBoer, D.J. Feline dermatophytosis.
Recent advances and recommendations for therapy.
In: Kunkle G. Feline dermatology. Veterinary Clinics
of North America: Small Animal Practice 1995; 25:
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3. Moriello, K.A., DeBoer, D.J. Efficacy of griseofulvin


and itraconazole in the treatment of experimentally
induced dermatophytosis in cats. Journal of the American
Veterinary Medical Association 1995; 207: 43944.
4. Hill, P.B., Moriello, K.A., Shaw, S.E. A review of systemic antifungal agents. Veterinary Dermatology 1995; 6:
5966.
5. Martin, S. Itraconazole. Compendium on Continuing
Education for the Practicing Veterinarian 1999; 2: 1457.
6. Cauwenbergh, G., Degreef, H., Heykants, J. et al. Pharmacokinetic profile of orally administered itraconazole
in human skin. Journal of the American Academy of
Dermatology 1988; 18: 2638.
7. De Doncker, P., Decroix, J., Pierard, G.E. et al. Antifungal pulse therapy for onychomycosis. A pharmacokinetic
and pharmacodynamic investigation of monthly cycles
of 1-week pulse therapy with itraconazole. Archives of
Dermatology 1996; 132: 3441.
8. De Doncker, P., Gupta, A., Marynissen, G. et al. Itraconazole pulse therapy for onychomycosis and dermatomycoses: an overview. Journal of the American Academy of
Dermatology 1997; 37: 96974.
9. Gupta, A.K., Hofstader, S.L.R., Summerbell, R.C. et al.
Treatment of tinea capitis with itraconazole capsule
pulse therapy. Journal of the American Academy of
Dermatology 1998; 39: 21619.
10. Havu, V., Brandt, H., Heikkila, H. et al. Continuous and
intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison.
British Journal of Dermatology 1999; 140: 96101.
11. DeBoer, D.J., Moriello, K.A. Inability of two topical
treatments to influence the course of experimentally
induced dermatophytosis in cats. Journal of the American
Veterinary Medical Association 1995; 207: 527.
12. Sparkes, A.H., Gruffydd-Jones, T.J., Stokes, C.R.
Acquired immunity in experimental feline Microsporum
canis infection. Research in Veterinary Science 1996; 61:
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13. DeBoer, D.J., Moriello, K.A. Development of an experimental model of Microsporum canis infection in cats.
Veterinary Microbiology 1994; 42: 28995.
14. Boothe, D.M., Herring, I., Calvin, J. et al. Itraconazole
disposition after single oral and intravenous and multiple
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15. Sparkes, A.H., Werrett, G., Stokes, C.R. et al. Microsporum canis. inapparent carriage by cats and the viability
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Rsum Cette tude a valu lefficacit de litraconazole dans le traitement des dermatophytoses flines en
utilisant une thrapeutique combine (continue/pulse). Neuf chats prsentant une dermatophytose due
Microsporum canis ont t traits avec litraconazole la posologie de 10 mg kg1 une fois par jour par voie orale
pendant 28 jours, puis avec un traitement puls (une semaine avec traitement, une semaine sans) au mme dosage.
Les chats ont subi un examen clinique et une culture fongique J28, J42, J56 et J70 si ncessaire. Le traitement
tait arrt lorsque deux cultures fongiques successives taient ngatives. Huit chats ont t guris aprs 56 jours,
avec deux cultures ngatives J28 et J42. Dans un cas, une culture positive a t observe J28, mais les cultures
nont t ngatives qu J42 et J56. Ce protocole apparat efficace pour le traitement des dermatophytoses flines,
bien que ces rsultats ne soient que prliminaires et ncessitent confirmation par une tude contrle.
2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 347350

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S. Colombo et al.
Resumen Este estudio evala la eficacia del itraconazol como terapia combinada continua/pulsada de la dermatosis felina. Se trataron nueve casos de dermatofitosis causada por Microsporum canis con itraconazol a
10 mg kg1 oralmente, una toma diaria durante 28 das y despus con un rgimen de semanas alternas (1 semana
sin terapia, 1 semana con terapia) con la misma dosis. Se reevaluaron los gatos mediante examen fsico y cultivo
fngico los das 28, 42, 56 y 70 cuando se estim necesario. Se par el tratamiento al obtenerse dos cultivos
fngicos negativos consecutivos. Se curaron ocho gatos a los 56 das, con dos cultivos negativos los das 28 y 42.
En un caso, se obtuvo un cultivo positivo el da 28, pero se consiguieron cultivos negativos los das 42 y 56. Este
protocolo parece ser efectivo en el tratamiento de la dermatofitosis felina, aunque estos resultados preliminares
deberan confirmarse mediante un estudio control.
Zusammenfassung Diese Studie bewertete die Wirksamkeit von Itrakonazol als kombinierte Dauer-/Pulstherapie
fr die Behandlung der felinen Dermatophytose. Neun Katzen mit durch Microsporum canis verursachter Dermatophytose wurden mit Itrakonazol in einer Dosierung von 10 mg kg1 oral einmal tglich fr 28 Tage und dann
jede zweite Woche mit derselben Dosierung behandelt. Wiederholungsuntersuchungen und Pilzkulturen wurden,
wenn ntig, nach 28, 42, 56 und 70 Tagen durchgefhrt. Die Behandlung wurde beendet, wenn zwei aufeinanderfolgende Pilzkulturen negativ waren. Acht Katzen waren nach 56 Tagen geheilt, die Pilzkulturen waren nach 28
und 42 Tagen negativ. Bei einer Katze war die Kultur am Tag 28 noch positiv, aber Kulturen waren nach 42 und
56 Tagen negativ. Dieses Behandlungsprotokol scheint fr die Behandlung der felinen Dermatophytose wirksam
zu sein, obwohl diese Resultate durch eine kontrollierte Studie besttigt werden sollten.

2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 347 350

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