The MIC of nystatin was determined for 1389 successive isolates of candida from clinical specimens, and of amphotericin B for 1307 successive isolates. A further 626 isolates of were tested for sensitivity to nystatin and a further 708 to amphotericin B. All these were shown to be sensitive. After gradual exposure on solid media to increased antibiotic concentrations, isolates of seven candida species became resistant to nystatin, amphotericin B, candicidin, pimaricin, and filipin. Compared with the polyene-sensitive parent isolates, the resistant cultures showed decreased growth rate, reduced production of germ tubes, slower production of chlamydospores, reduced suspension stability, reduced ergosterol content, and reduced pathogenicity. Isolates resistant to one polyene were found to show cross-resistance to other polyenes. The fluctuation and Newcombe tests suggested that the development of resistance was due to mutation. Resistant isolates showed reversion to sensitivity and some return of their normal properties when no longer exposed to polyenes. There was no evidence of the transfer of resistance from one isolate to another.


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