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In vitro activity of amphotericin B, hamycin and their novel water-soluble compounds against pathogenic yeasts
A S Sekhon1, A A Padhye, A K Garg
1National Reference Centre for Human Mycotic Diseases, Provincial Laboratory of Public Health, University of Alberta, Edmonton, Canada.
Abstract:
Twenty-eight pathogenic isolates, 4 each of Candida albicans, C. lusitaniae, C. parapsilosis, Cryptococcus neoformans, Torulopsis glabrata and Trichosporon beigelii were tested for their in vitro sensitivity to amphotericin B (AmB), hamycin (HA) and their novel water-soluble compounds, namely JAI-AmB (oral and injectable; patents pending) and JAI-HA (Jaimycin Inc., Walnut Creek, Calif., USA), using a standard double-dilution broth (1 ml/tube) procedure. The 2 novel compounds, namely JAI-AmB and JAI-HA, contain one twenty-fifth (w/w) of the AmB and HA, respectively. Results showed that the minimal inhibitory concentrations (MICs) of AmB for all species, except C. lusitaniae and Tr. beigelii (3.125-6.25 micrograms/ml), were 0.195-1.56 micrograms/ml. The values of JAI-AmB (oral) for C. albicans, C. parapsilosis, Cr. neoformans and To. glabrata ranged from 0.78 to 25 micrograms/ml. The MICs of JAI-AmB (oral) for the other yeasts were 100 micrograms/ml. All of the yeasts yielded higher MICs (3.125-100 micrograms/ml) against JAI-AmB (injectable) than the JAI-AmB (oral) preparation. Except for C. parapsilosis (MICs 25-100 micrograms/ml), all of the other species showed greater sensitivity to the parent HA (0.195-100 micrograms/ml) than AmB. The values for JAI-HA ranged from 0.195 to 100 micrograms/ml for all isolates, except C. tropicalis (100 micrograms/ml). Based on our in vitro findings, in vivo efficacies of JAI-AmB and JAI-HA should be carried out.
Insights
Novel water-soluble antifungal compounds, JAI-AmB and JAI-HA, show varied in vitro activity against pathogenic yeasts. Further in vivo studies are recommended to assess their efficacy.
Area of Science:
- Mycology
- Antimicrobial Agents
Background:
- Pathogenic yeasts like Candida and Cryptococcus pose significant clinical challenges.
- Existing antifungal therapies, such as amphotericin B (AmB) and hamycin (HA), have limitations.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of novel water-soluble derivatives, JAI-AmB and JAI-HA, against key pathogenic yeast isolates.
- To compare the efficacy of these novel compounds with their parent drugs, AmB and HA.
Main Methods:
- A standard double-dilution broth microdilution method was employed.
- Twenty-eight pathogenic yeast isolates, including Candida albicans, Cryptococcus neoformans, and others, were tested.
- Minimal Inhibitory Concentrations (MICs) were determined for AmB, HA, JAI-AmB (oral and injectable), and JAI-HA.
Main Results:
- AmB demonstrated MICs of 0.195-1.56 µg/ml against most yeasts, except C. lusitaniae and Tr. beigelii.
- JAI-AmB (oral) showed variable MICs (0.78-100 µg/ml), while the injectable form had higher MICs.
- JAI-HA exhibited broad activity (0.195-100 µg/ml), with greater sensitivity observed for HA compared to AmB against most species.
Conclusions:
- The novel water-soluble compounds JAI-AmB and JAI-HA display distinct in vitro antifungal profiles.
- Results suggest that JAI-HA may offer a broader spectrum of activity compared to JAI-AmB.
- Further in vivo investigations are warranted to ascertain the clinical potential of JAI-AmB and JAI-HA.