P-27530: In vitro evaluation of antifungal activity against a broad spectrum of yeast and filamentous fungi: investigation of the evolution of resistance in Trichophyton rubrum

Ref ID: 19375

Author:

L. A. Long,1 N. Isham,1 G. Stoll,1 S. A. Gueye,2 E. Ghelardi,2 F.
Celandroni,2 F. Mailland,3 A. Bulgheroni3 and M. A. Ghannoum1

Author address:

1Case Western Reserve University, Cleveland, USA; 2Department
of Translational Research NTMS, University of Pisa, Italy and
3Polichem SA, Lugano-Pazzallo, Switzerland

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives (1) To evaluate the antifungal activity of P-27530
against a broad range of yeast and filamentous fungi, by minimum
inhibitory concentration (MIC) assay. (2) To evaluate the natural
resistance frequency and the evolution to resistance of P-27530 in T.
rubrum, compared to amorolfine, terbinafine, itraconazole and
ciclopirox.
Methods (1) Test isolates included 5 clinical isolates each (3 suscep-
tible and 2 resistant strains where possible) of yeasts (Candida albi-
cans, C. glabrata, C. parapsislosis, C. krusei, C. lusitaniae, C. tropicalis
and Cryptococcus neoformans), moulds (Fusarium solani, Aspergillus fla-
vus, A. fumigatus, A. niger, A. terreus, Pseudallescheria boydii, Scopulari-
opsis brevicaulis, Scedosporium spp., S. prolificans, Cunninghamella
bertholletiae, Rizopus oryzae, Mucor plumbeus, M. fragilis) and dermato-
phytes (Trichophyton rubrum, T. mentagrophytes, Epidermophyton flocco-
sum, Microsporum canis). MIC testing was performed according to the
CLSI M27-A3 and M38-A2 standards for the susceptibility testing of
yeasts and filamentous fungi, respectively. (2) The frequency of spon-
taneous resistance of 3 T. rubrum strains was evaluated by counting
the number of colonies obtained following incubation of agar plates
inoculated with a total of about 109 CFU on agar plates containing drug concentrations higher than the minimal fungicidal concentra-
tion; the evolution of resistance was evaluated in 2 T. rubrum strains
serially propagated for 10 transfers on agar plates containing sub-
inhibitory drug concentrations. After the 5th and the 10th transfer,
colonies were transferred on plates containing inhibitory drug con-
centrations and assessed for growth following incubation.
Results (1) The in vitro susceptibility of the tested strains to P-
27530 was as follows: Yeasts P-27530 MIC range of 0.06-1 lg/ml
was recorded, following 24 hours incubation, for all yeasts but sev-
eral C. glabrata isolates which were read at 48 hours (MIC range of
0.06-2 lg/ml). P-27530 performed similarly against both Candida
susceptible strains and strains resistant to caspofungin, fluconazole,
miconazole, and voriconazole. Slightly reduced activity was
observed against Cryptococcus neoformans with a MIC range of 2-
4 lg/ml. Moulds P-27530 performed similarly against the suscepti-
ble strains and the strains with elevated MICs to amphotericin B,
caspofungin, itraconazole, and miconazole with a MIC range of
0.06-2 lg/ml. Dermatophytes P-27530 demonstrated similar activ-
ity against the isolates (range of 0.25-2 lg/ml) and performed simi-
larly (within one dilution) against both susceptible and resistant
(terbinafine and fluconazole) T. rubrum and T. mentagrophytes
strains. (2) no spontaneous resistant mutant to P-27530 and CPX
was isolated; resistance frequency was 107 for itraconazole and
109 for terbinafine and amorolfine. All mutants collected con-
firmed the loss of susceptibility. P-27530 and CPX did not induce
any resistance; frequency was 105 for itraconazole and 107 for
terbinafine and amorolfine. In both experiments itraconazole resis-
tant mutants showed increased resistance also to amorolfine and
terbinafine.
Conclusions P-27530 shows a good antifungal activity in vitro
against a broad spectrum of yeasts, moulds and dermatophytes, with-
out evidencing any cross-resistance potential. Moreover, the lack of
resistant mutant isolation in the in vitro assays suggests a low pro-pensity of T. rubrum to develop resistance against P-27530.

Abstract Number: p007

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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