RESISTANCE OF FUNGI TO POLYENE ANTIBIOTICS

It is often stated that resistance to polyene antibiotics does not occur [103, 299—301). It is perhaps more true to say that although yeasts and other fungi are capable of giving rise to polyene-resistant strains, polyene resistance has not become a clinical problem, even after twenty years of therapeutic use. This is fortunate, for an increase in resistance of twenty-fold would be sufficient to render many strains of pathogenic and opportunistic fungi resistant to antibiotic concentrations that can be achieved in clinical lesions by conventional polyene therapy. 

In vitro polyene resistance has been demonstrated in yeasts [301-311], dermatophytes [312,313], Aspergillus sp. [314] and Neurospora sp. [315]. Resistance to polyenes does not confer resistance to non-polyene antifungal 

Relatively few reports exist of in vivo acquisition of polyene resistance and those cases reported only possessed low levels of resistance (three to four times the minimum inhibitory concentration) [336,337]. Examination of large numbers of clinical isolates of C. albicans has failed to demonstrate resistance to 

A series of papers [305—310,323] examined the genetics of polyene resistance in S. cerevisiae and suggested that nystatin resistance was controlled by three recessive genes and two dominant modifiers. Thf genes that gave rise to the s-l, nys-2 and nys-3 mutants differed markedly in their ability to give crossresistance to filipin and amphotericin B, nys-l confered resistance to amphotericin B and nystatin but not to filipin, while nys-2 and nys-3 confered resistance to nystatin and filipin but made the yeasts hypersensitive to amphotericin 

Similar discrepancies in polyene cross-resistance have also been described for 

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