Full professor of Internal Medicine-FMVz/USP, Av. Prof. Dr. Orlando Marques de Paiva
São Paulo, Brasil
SYSTEMIC THERAPY 1,2,3,4,5,6,7
Over the past two decades, immunocompromise associated with virus infection immunodeficiency or iatrogenic diseases lead to the appearance of fungal infections till then unknown, and also to great changes in the diseases caused by these agents. This fact determined the search for more effective and less toxic new drugs or alternative therapy protocols for superficial, subcutaneous and systemic infections. The regular antifungals (amphotericin ß and azoles) target the ergosterol, an essential component of molds cell membrane. These drugs have major affinity to fungal cell membrane ergosterol than to cholesterol in mammalian cell membrane. For this reason, compounds that interfere with the synthesis of important fungal cell wall components (ß glucan, chitin) have recently become a focus in the development of new antifungal agents2.
However, many classic protocols are still in use, since they are efficient, cheap and no severe collateral effects. This is true mainly to the first of the systemic antifungals developed in the sixties, utilized in the dermatophytosis therapy, which are the grisane derivates (griseofulvin).
In summary, antifungals are classified according to their target in:
Antifungals with antimycotic activity: griseofulvin
Antifungals with activity on ergosterol: amphotericin, azoles and terbinafine
Antifungals with activity on proteic synthesis: sodarins
Antifungals with activity on nucleic acid synthesis: flucytosine
Antifungals with activity on ß- glucans synthesis: echinocadins, pneumocandins
Antifungals with activity on chitin synthesis: lufenuron, nikkomycins.
The common protocol for treating sporotrichosis uses "per os" halogenated drugs, like sodium or potassium iodide, 20% super saturated solution. French researchers proposed iodine to treat human and animal sporotrichosis in the 19th century, and even nowadays, it is extremely effective in human, canine and equine patients5. Doses of 40 mg/kg or 10-20 mg/kg once a day, "per os" are indicated to dogs and cats, respectively, always with food or fatty liquid (cream or whole milk)7. The metallic taste is extremely unpleasant, so nausea or emesis may be observed. Iodism is not rare in cats.
Although the traditional reference about its efficacy in feline sporotrichosis, this is not true in Brazil. Up to 1993, all cats were unsuccessfully treated with NaI or KI at Veterinary Teaching Hospital of FMVZ-USP. Over the last 9 years, itraconazole has been successfully used (10 mg/kg, "per os", q24h), alone or associated with fluocytosine (40-60 mg/kg, "per os", q24h). The only disadvantages of this protocol are the necessary time to get cure (until 7 months of treatment), and its cost7.
In some cases terbinafine has been recommended although there is no recommended standard doses 2,7.
The common protocol is the same recommended for feline sporotrichosis, that is, the single use of itraconazole or in association with flucytosine (5-fluorocytosine), in the same preferred doses. A long period of treatment (6-12 months) guarantees the success, particularly in feline and canine neuroophtalmopaties1.
Recently, cases of toxic epidermal necrolysis associated with therapy regimens using flucytosine in association with amphotericin ß or triazols were described. Circumstantial evidences strongly suggest that is fluocytosine component of therapy which triggered this response6. This side effect has not been observed in several cases treated with this drugs association in São Paulo1, and oppositely to what referred in the literature, any case of FeLV or FIV seropositive cat responded unsuccessfully to triazol-pyrimidine association when compared with seronegative ones1.
Alternatively, ketoconazole (dog: 5-15 mg/kg, q12h, PO; cat: 5-10 mg/kg, q12h, PO); fluoconazole (50 mg/cat/day for nasal and dermal cryptococcosis, and 2,5-10 mg/kg/day for cryptococcal meningitis); -ß lipid complex-ABLC- (dog: 2-3 mg/kg, IV, 3 days/week, for 9-12 treatments; cat: 1 mg/kg, IV, 3 days/week for a total of 12 treatments) are recommended 2,3,4.
In all cases cryptococcosis in cats as well in dogs (rare in Brazil), the use of itraconazole (alone or in association with flucytosine) was effective and with no side effects.
Pythiosis treatment is extremely difficult. In large animals, the use of vaccine as a therapy for the disease has successful results in 60% of cases. However, there is no data regarding the effectiveness of this kind of therapy in dogs and cats affected by Pythium sp.
Generally, cryotherapy or wide surgical excision is recommended in localized cutaneous forms with no metastasis although the recurrence is not uncommon. Sometimes amputation of the affected limb is necessary. Because Pythium do not share cell wall characteristics with true fungi, antifungal therapy has shown disappointing results in the disease treatment. Nowadays amphotericin (ABLC) or association of terbinafine and itraconazole has been indicated 2,3.
1. Chiesa, S.C. Criptococose felina: aspectos clínico-epidemiológicos. São Paulo (Brasil), 1998. 94 p. Dissertação (Mestrado). Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo.
2. Grooters, A.M. Advances in antifungal therapy. In: AAVD/ACVD Meeting, 17th, New Orleans/USA. Proceedings, 2002. p. 79-83.
3. Grooters, A.M. Systemic mycoses with dermatologic manifestations. In: AAVD/ACVD Meeting, 17th, New Orleans/USA. Proceedings, 2002. p. 73-8.
4. Jacobs, G.J.; Greene, C.E.; Medleau, L. Criptococosis felina y canina. WALTHAM FOCUS, v. 8, n. 4, p. 21-7, 1998.
5. Larsson, C.E. Dermatozoonosis. In: Congress Of The World Small Animal Veterinary Association, 23rd, 1998, Buenos Aires/Argentina. Proceedings, P. 25-8.
6. Malik, R.; Martin, P.; Wigney, D.I. Unusual dermatoses caused by or triggered by microorganisms. In: AAVD/ACVD Meeting, 17th, New Orleans/USA. Proceedings, 2002. p. 106.
7. Scott, D.W.; Miller Jr., W.H.; GRIFFIN, C.E. In: Muller & Kirk's Small Animal Dermatology. 6 ed., Philadelphia, Saunders, p. 381-84, 395-400, 2001.