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   Abstract
   Introduction
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STUDIES
Year : 1992  |  Volume : 58  |  Issue : 6  |  Page : 368-371

In vitro susceptibility of dermatophytes to itraconazole




Correspondence Address:
V Pankajalakshmi Venugopal


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  Abstract 

The in vitro activity of itraconazole was investigated against 88 clinical isolates of dermatophytes. The isolates included Microsporum canis-50, M. audovinii-5, Trichophyton rubrum-6, T. mentagraphytes-5 T.violaceum-12, T.simii-5, T verrucosum-1, T.soundanense-1, T. erinacei-1 and Epidermophyton flooccosum-2 isolates. The results were compared with that of ketoconazole and griseofulvin. Itraconazole was more active, inhibiting 85 of the 88 isolates at a concentration of 0.5 g/ml (MIC range 0.01-1 g/ml). Ketoconazole (MIC range 0.1-10 g/ml) required 2.5 g/ml and 5 g/ml of the drug respectively for inhibition of all the isolates except one of Microsporum species.


Keywords: Dermatophytes, Itraconazole


How to cite this article:
Venugopal V P, Venugopal T. In vitro susceptibility of dermatophytes to itraconazole. Indian J Dermatol Venereol Leprol 1992;58:368-71

How to cite this URL:
Venugopal V P, Venugopal T. In vitro susceptibility of dermatophytes to itraconazole. Indian J Dermatol Venereol Leprol [serial online] 1992 [cited 2019 Oct 15];58:368-71. Available from: http://www.ijdvl.com/text.asp?1992/58/6/368/3854



  Introduction Top


Itraconazole, a new oral triazole derivative, has a broad spectrum of antifungal activity. In vitro, it is active against dermatophytes, yeasts, Aspergillus and dimorphic fungi.

We evaluated the in vitro activity of itraconazole against 88 clinical isolates of dermatophytes by agar dilution method. The results were compared with those of ketoconazole and griseofulvin.


  Materials and Methods Top


Drugs : Itraconazole and ketoconazole were obtained from Janssen pharmaceutical and griseofulvin from IDPL in pure powder form. Stock solution of itraconazole was prepared by initially dissolving 10mg of the drug in 0.5 ml of dimethyl sulfoxide and then adding 9.5 ml of distilled water. Ten mg of ketoconazole was dissolved in 0.2 ml of 0.2 NH 4 C1 and 9.8 ml of distilled water. Griseofulvin was dissolved in 10 ml of 70% ethanol. Further dilutions were made in distilled water and 2 ml of each drug dilution were added to 18 ml of nutrient agar and dispensed in tubes. The final drug concentrations in the medium were 100 - 0.0001 g/ml from tube 1 through tube 10. The drug-free medium and medium supplemented with the solvents were used as controls.

Test fungi and preparation of inocula : A total of 88 isolates of dermatophytes, from clinical cases of tinea capitis, tinea corporis or tinea cruris were tested in this study. They consisted of 55 isolates of Microsporum species, 31 isolates of Trichophyton species and 2 isolates of E.floccosum. The fungi were subcultured on sabouraud's dextrose agar and incubated at 35C for 7-14 days. The growth was scraped with a thick wire and crushed and macerated thoroughly in a sterile pestle and mortar. Ten ml of sterile distilled water was added and the fungal suspension was standardized spectrophotometrically to an absorbance of 0.600 at 450 rm. [1]

Susceptibility testing : The drug containing tubes along with the controls were inoculated with 10 l of the standardized inoculum of each isolate and incubated at 30c. The lowest concentration of the drug which permitted no macroscopically visible growth after 7 days was taken as the minimum inhibitory concentration (MIC). Each test was performed in triplicate. The MICs reported represent the results of atleast 2 replications.


  Results Top


The results are given in [Table - 1][Table - 2][Table - 3] of the 88 isolates tested (10 species of Microsporum, Trichophyton and Epidermophyton) 50 were sensitive to itraconazole at a concentration of 0.1.tg/ml and 85 at 0.5 gg/mI. Only 2 isolates of M.canis and 1 of T. violaceum required 1 g/ml of the drug for inhibition (MIC range 0.01-1). Ketoconazole required 1 pg/ml to inhibit 71 isolates and 2.5g/ml for 87 isolates. One isolate of M.audouinii had an MIC of 5 gg/ml. Griseofulvin had inhibited 50% of the isolates at an MIC of 1 .ig/ml. All, except one M.canis isolate, which had an MIC of 10 g/ml, were inhibited at 5 g/ml of the drug.


  Comments Top


The results show that itraconazole was more active than ketoconazole or griseofulvin against dermatophytes (MIC range 0.01 - 1 g/ml). Our findings are consistent with those of other workers. [2],[3],[4] Van Cutsem et al, [2] while testing 271 strains of dermatophytes in brain-heart infusion broth have reported 95% of them to be sensitive to 0.1 .tg/ml of itraconazole. Espinel-Ingroff et al, [3] in their studies on 30 isolates of dermatophytes in Kimmig's agar reported inhibition of 50% of the isolate at 0.13 gg/ml and 90% at 0.25 tg/ml (MIC range 0.063 - 64 g/ml) or itraconazole, whereas ketoconazole required 0.5 g/ml and 2 .tg/ml for inhibition of 50% and 90% of the isolates (MIC range 0.063 - 4 gg/ml). Shadomy et al, [4] have reported an MIC range of < 0.06 - 1 gg/ml and inhibition of 50% of the 24 isolates of dermatophytes at 0.13 g/ml and 90% at 0.5 g/ml by agar dilution in kimmig's agar and the figures for ketoconazole are < 0.06-2, 0.13 and 1 .tg/ml respectively.

Itraconazole has been licensed to treat patients with vaginal candidiasis, tinea infections of the skin or pityriasis versicolor in the United kingdom and open clinical trial have shown that it is effective against these infections. [5]

However, itraconazole should be reserved for patients with infections that fail to respond to standard drugs.


  Acknowledgement Top


We thank the Janssen Pharmaceutical (Belgium) and IDPL for kindly providing the drugs.

 
  References Top

1.Granade TC, Artis WM: Artimynotic susceptibility testing of dermatophytes in microcultures with a standardized fragmented mycelia) inoculum. Antimicrob Agents Chemother 1980 ; 17 : 725 - 9.  Back to cited text no. 1    
2.Van Cutsem J, Van Gerven F, Janssen PAJ. Activity of orally, topically and parenterally administered itraconazole in the treatment of superficial and deep mycoses. Animal models. Rev Infect Dis 1987; 9: s 15- 32.  Back to cited text no. 2    
3.Espinel Ingroff A, Shadomy s, Gebhart RJ. In vitro studies with R 51.211 (Itraconazole), Antimicrob Agents Chemother 1984; 26: 5-9.  Back to cited text no. 3    
4.Shadomy S, Espinel - Ingroff A, Gebhart RJ. In vitro studies with SF 86 - 327, a new orally active allylamine derivative J Med Vet Mycol 1985; 23: 125 - 32.  Back to cited text no. 4    
5.Devey PG. New antiviral and antifungal drugs. BMJ 1990; 300: 793 - 8.  Back to cited text no. 5    


    Tables

[Table - 1], [Table - 2], [Table - 3]



 

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