The antifungal activity of F901318, a new antifungal agent from the novel orotomide class

Embargoed Until: 11:00 am PST, Saturday, September 19, 2015

Author: Michael Birch
Control Number: 2385

This study tested the potency of the new antifungal drug F901318 against a large number of Aspergillus strains (221) which had been recovered from infected patients in the UK and in Austria. All the strains tested were highly susceptible to the new antifungal agent F901318 with no resistant isolates found. In contrast, several of the isolates tested showed resistance to drugs currently used to treat Aspergillus infections.

The shows that F901318 has good potential to treat Aspergillus infections and may be particularly useful to treat infections when the strain is resistant to other available drugs.

Serious fungal infections typically occur in patients with damaged or impaired immune systems. Aspergillus is a common mould found in the environment that produces tiny spores which when inhaled can enter the lungs. Without an immune system to clear the spores they can germinate and start to invade tissues ultimately leading to a life-threatening infection. Currently only three classes of drug are available to treat these types of infection and Aspergillus is becoming increasingly resistant to some of them.

We have discovered an entirely new class of antifungal drugs which we have called the orotomides. The leading member of this new class of drugs is F901318 and we have tested it in the laboratory against a large panel of Aspergillus strains which were recovered from patients in Austria and the UK. Four species of Aspergillus were tested which represent the most common species recovered from infections in man. We used standard testing methods to determine the minimum concentration of drug which inhibits growth of the fungus (Minimum Inhibitory concentration MIC) and our study compared the activity of F901318 against marketed drugs currently used to treat Aspergillus infections.

All the Aspergillus isolates tested (A. fumigatus n= 80, A. terreus n = 45, A. flavus n=50 and A. niger n=46) were highly susceptible to F901318 with all MICs < 0.03 mg/L.

We found no strains that were resistant to F901318 or had raised MIC levels. In contrast, several of the A. fumigatus and A. niger strains had increased MIC levels to the azole antifungal drugs and these strains would be considered resistant to these drugs. Similarly we found high MICs to Amphotericin B amongst the A. terreus and A. flavus strains which would also be considered resistant.

These data demonstrate that F901318 has potent activity against a range of pathogenic Aspergillus species isolated from patients and that F901318 could be used to treat Aspergillus infections particularly those in which resistant pathogens are found.

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