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STUDIES
Year : 1993  |  Volume : 59  |  Issue : 5  |  Page : 239-242

Antifungal activity of allylamines against agents of eumycetoma



Correspondence Address:
Taralakshm Venugopal


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  Abstract 

The antifungal activity of the two allylamines naftifine and terbinafine was investigated against 22 strains of eumycetes isolated from cases of eumycetoma by agar dilution. The isolates included Madurella mycetomatis (4), M. Grisea (8), Pyrenochaeta romeroi (2), Exophiala jeanselmei (2) and Leptosphaeria tompkinsii (1) from black grain eumycetomas and Pseudalescheria boydii (3) Acremonium kiliense (1) and A. recifei (1) form pale grain eumycetomas. Terbinafine was more active than naftifine inhibiting 50% (MIC50) and 90% (MIC90) of the black grain eumycetoma agents at 0.5 and 2.5 ?g/ml respectively. The MIC50s and MIC90s of naftifine were 1 and 5 ?g/ml. For pale grain eumycetoma agents, the MIC range for terbinafine and naftifine were ??0.01 - 100 and 0.1 - 100 ?g/ml.


Keywords: Allylamines, Eumycetoma


How to cite this article:
Venugopal T. Antifungal activity of allylamines against agents of eumycetoma. Indian J Dermatol Venereol Leprol 1993;59:239-42

How to cite this URL:
Venugopal T. Antifungal activity of allylamines against agents of eumycetoma. Indian J Dermatol Venereol Leprol [serial online] 1993 [cited 2019 Sep 17];59:239-42. Available from: http://www.ijdvl.com/text.asp?1993/59/5/239/3943



  Introduction Top


Allylamines are the newest group of synthetic antibiotics which act by inhibition of squalene epoxidase in the formation of fungal cell membrane. The two main compounds, naftifine and terbinafine are highly active in vitro against a wide range of fungi. [1],[2],[3],[4],[5] Since susceptibility studies of these drugs against the causal agents of eumycetoma are very few, we decided to evaluate the antifungal activity of naftifine and terbinafine (Sandoz Forchungs institute) against the agents of eumycetoma by using a standardised, fragmented inoculum in microcultures. Simultaneous testing was undertaken using the agar dilution method for comparison.


  Materials and Methods Top


Stock solutions of naftifine and terbinafine were made by initially dissolving 11 mg of the drug in 0.5ml of dimethyl sulfoxide and then adding 4.5 ml of distilled water. Further dilutions were made in distilled water so that 10 l of each dilution, when added to the microtiter wells, the indicated final concentration was achieved. The final drug concentrations were as follows 100,20,10, 5, 2.5, 1, 0.5, 0.1, 0.05 and 0.01 lug/ml.

The test organisms were clinical isolates from cases of eumycetoma. Two of the M. mycetomatis strains and the A. kiliense strain were isolated from patients treated at the Government General Hospital, Madras and they had been deposited at the American Type culture collection (ATCC 62382, 62383, 62384). The L. tompkinsii strain was isolated from a patient admitted to the Rajah Mirasdar Hospital, Thanjavur,

Tamil Nadu and it has been identified as Leptosphaeria sp., by the Common Wealth Mycological Institute (IML 281764). and L. tompkinsii by the American Type Culture Collection (ATCC 62381). One M. mycetomatis strain was obtained from the National Institute of Communicable Diseases, New Delhi. The rest of the strains were from the Calcutta School of Tropical Medicine, Calcutta, The preparation of the inocula and susceptibility testing by broth microdilution and agar dilution were performed and data obtained as previously described. [6]


  Results Top


The MICs determined by broth dilution are shown in [Table - 1] a, b. Terbinafine was more active than naftifine with an MIC value ranging from <0.01 - 2.5 g/ml for black grain eumycetoma agents and < 0.01 - 100 g/ml for pale grain eumycetoma agents whereas the values for naftifine were <_ 0.01 - 5 and 0.1 - 100 g/ml respectively. The MIC values were generally 1 dilution lower by broth dilution method than by agar dilution method.


  Comments Top


Though the allylamines are inhibitory in vitro against a number of pathogenic fungi, only very few strains of the causal agents of eumycetoma have been tested for their susceptibility to these drugs. Our results show that the agents of black grain mycetoma were sensitive in vitro to the allylamines and terbinafine was more active than naftifine.

The MIC50S and MIC 90s of terbinafine for agents of black grain eumycetoma were 0.5 and 2.5 g/ml. When compared with the azoles, ketoconazole, itraconazole, miconazole and econazole, the activity of terbinafine is similar to that of itraconazole which had the same MIC range (< 0.01 - 2.5) as well as the value for MIC 50 and MIC 90 . [6] The MIC50s and MIC 90s of naftifine for black grain eumycetoma agents were 1 and 5 g/ml.

For the pale grain eumycetoma agents, although the allylamines have inhibited one strain each of A. kiliense and A. recifei at an MIC of 0.01 and 1 g/ml of terbinafine and 0.1 and 2.5 g/ ml of naftifine, they are least active with the strains of P. boydii. The MIC range of terbinafine and naftifine for the 3 strains ,)f P. boydii tested were 10 - 100 and 20 - 100 p.g/ml. Shadomy et a1 [3] have also reported an MIC range of 32 - 64 g/ml of terbinafine with 50% and 90% inhibition at 64 g/ml for the 5 isolates of P. boydii tested. Their values for naftifine ranged from 16 - 64 with MIC50 and MIC 90 as 16 and 64 g/ml. [3] Clayton also has reported that P. boydii strains were not susceptible to terbinafine. [7]

The in vitro data presented indicate that the allylamines, especially terbinafine is highly active against the agents of black grain eumycetoma. Since terbinafine possesses an highly selective mode of action, can be administered orally and preliminary studies in humans indicate that it is well tolerated, the drug will be very useful for long term therapy of black grain eumycetoma, once it becomes more widely available.


  Acknowledgements Top


This work was supported by a grant from the Indian Council of Medical Research with an award of Research Sabbatical to Prof. Pankajalakshmi V Venugopal and Junior Research Fellowships to E S Ramakrishna and S Ilavarasi. We thank the Sendoz Forchungs institute (Austria) for kindly providing the test drugs. We are greatly indebted to Dr Thammayya, Calcutta School of Tropical Medicine, Calcutta for the provision of his strains.

 
  References Top

1.Georgopoules A, Petranyi, G, Mieth H, et al. In vitro activity of naftifine, a new antifungal agent. Antimicrob Agents Chemother 1981 ; 19 : 386 -9.  Back to cited text no. 1    
2.Stutz A, Petranyi G. Synthesis and antifungal activity of (E) - N - (6,6 - Dimethyl - 2 - Hepten - 4 - ynyl) - N - methyl - 1-napthalenemethanamine (SF 86 - 327) and related allylamine derivatives with enhanced activity. J Med Chen 1984 ; 27 : 1539 - 43.  Back to cited text no. 2  [PUBMED]  
3.Shadomy S, Expinel - Ingroff A, Gebhart J. 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. 3    
4.Goudard M, Buffard Y, Ferrari H, et al. Spectre d'action in vitro d' Un nouvel antifungique derive de la naftifine ; la terbinafine (SF 86 - 327). Pathol Biol (Paris) 1987 ; 34 : 680 - 3.  Back to cited text no. 4    
5.Petranyi G, Meingassner JG, Mieth H. Antifungal acrtivity of the allylamine derivative terbinafine in vitro. Antirnicrob Agents Chemother 1987 ; 31 : 1365 - 8.  Back to cited text no. 5    
6.Pankajalakshmi V Venugopal, Taralakshmi V Venugopal, Ramakrishna E S, et al. Antimycotic susceptibility testing of agents of black grain eumycetoma. J Med Vet Mycol 1993 ; 31 : 141 - 4.  Back to cited text no. 6    
7.Clayton Y M. In vitro activity of terbinafine. Clin Exp Dermatol 1989 ; 14 : 101-3.  Back to cited text no. 7    


    Tables

[Table - 1]

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