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Journal of Clinical Microbiology, November 2001, p. 4208-4209, Vol. 39, No. 11
Istituto di Malattie Infettive e Medicina
Pubblica1 and Clinica
Dermatologica,2 Università degli Studi
di Ancona, Ancona, Italy
Received 9 March 2001/Returned for modification 1 April
2001/Accepted 3 September 2001
A broth macrodilution method following the
recommendations established by the National Committee for
Clinical Laboratory Standards was used to compare the in vitro activity
of posaconazole (PCZ) with that of itraconazole (ITC) against 30 clinical isolates of dermatophytes belonging to six different species.
In terms of MICs, PCZ showed an activity equal to that of ITC. MICs of
PCZ at which 50% (MIC50) and 90% (MIC90) of
the isolates were inhibited were 0.5 and >4.0 µg/ml, respectively.
The MIC50 and MIC90 of ITC were 1.0 and >4.0
µg/ml, respectively. However, PCZ showed a more potent
fungicidal activity than that of ITC against isolates belonging to the
genus Microsporum (P = 0.03). PCZ merits
further investigation as a potentially useful agent for treatment of dermatophytosis.
Cases of dermatophytosis have
increased over the past few decades (11). These infections
are often recalcitrant to therapy (4, 11). In the last few
years, several antifungal agents, such as itraconazole (ITC), have
become available for the treatment of these infections. Posaconazole
(PCZ) is a new antifungal triazole with potent activity against yeasts
and filamentous fungi that cause systemic infections (1, 7,
10). Whether this new triazole is active against dermatophytes
is still unknown. In this study, we compared the in vitro activity of
PCZ with that of ITC against clinical isolates of dermatophytes.
Thirty clinical isolates were collected over a 1-year period in the
Department of Dermatology of the University of Ancona, Ancona, Italy.
They included 16 strains of Microsporum canis, 6 strains of
Trichophyton rubrum, 4 strains of Trichophyton
mentagrophytes, 2 strains of Epidermophyton floccosum,
and 1 strain each of Trichophyton verrucosum and
Microsporum gypseum. All isolates were identified by
standard methods, which included identification based on the macroscopic and microscopic characteristics of the cultured strains (5). Additional tests included those for the ability to
produce a red pigment when the strains were grown on potato dextrose
agar and for the ability to produce urease, as well as the hair
perforation test. Both ITC (Janssen, Beerse, Belgium) and PCZ
(Schering-Plough Research Institute, Kenilworth, N.J.) were provided as
pure powders by their respective manufacturers. Stock solutions of both
drugs were prepared in polyethylene glycol 400 (Janssen Chimica, Geel, Belgium). Further dilutions were prepared in the test medium. Both
triazoles were tested at concentrations ranging from 0.0078 to
4.0 µg/ml. Testing was performed by a broth macrodilution method following the recommendations of the NCCLS (2, 6). In
brief, stock inocula of the molds were prepared from 7- to 14-day
cultures grown on potato dextrose agar at 30 to 35°C. Mature colonies
were covered with approximately 2 to 3 ml of sterile water, and
suspensions were made by gently scraping the colony with the tip of a
sterile pipette. The resulting suspended mixture was withdrawn and
transferred to a sterile tube. Heavy particles of the suspension were
allowed to settle for 5 min, and the upper homogeneous suspension was used for further testing. After the suspensions were mixed with a
vortex mixer, their densities were read at a wavelength of 530 nm and
adjusted to 95% transmittance. The suspensions containing conidia and
hyphal fragments were diluted 1:10 with RPMI 1640 medium buffered to pH
7.0 with 0.165 M morpholinepropanesulfonic acid (MOPS) to obtain an
inoculum size of approximately 104 CFU/ml. Tubes were
incubated at 30°C. Readings were performed every day until the
control tube showed visible growth. Incubation ranged from 6 to 10 days
for isolates belonging to the genus Microsporum, E. floccosum, and T. mentagrophytes. Incubation ranged
from 15 to 20 days for isolates of T. rubrum and T. verrucosum. The MIC of both triazoles was defined as the lowest
drug concentration which resulted in an 80% reduction in turbidity
compared to that of a drug-free control tube (2, 3, 8, 9).
For determining the minimal fungicidal concentration (MFC), 100 µl of
suspension was taken from those tubes exhibiting no growth and
subcultured onto Sabouraud dextrose agar plates. The plates were
incubated at 30°C until the growth of subcultures was visible. The
MFC was defined as the lowest drug concentration at which no fungal
growth was visible. A clinical isolate of T. rubrum was
included in each experiment. All isolates were tested twice against
both drugs.
Table 1 summarizes the in vitro
susceptibilities of 30 clinical isolates of dermatophytes to ITC and
PCZ. The MICs of ITC and PCZ ranged from 0.06 to >4.0 µg/ml and from
0.015 to >4.0 µg/ml, respectively. ITC MICs at which 50% and 90%
of the isolates were inhibited were 1.0 and >4.0 µg/ml,
respectively. For PCZ, these concentrations were 0.5 and >4.0 µg/ml,
respectively. When the Mann-Whitney U test was used to determine the
distribution of triazole MICs, no significant difference was found
(P = 0.136). In general, isolates belonging to the
genus Microsporum proved to be significantly more
susceptible than those belonging to the genus Trichophyton
to both ITC (P = 0.001) and PCZ (P = 0.0001). The MFCs of ITC and PCZ ranged from 2 to >4.0 µg/ml
and from 0.5 to >4.0 µg/ml, respectively. Although both drugs were
equally effective against isolates belonging to the genus
Trichophyton in terms of fungicidal activity, PCZ exerted a
more potent activity than ITC against isolates belonging to the genus
Microsporum (P = 0.03).
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.11.4208-4209.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
In Vitro Activity of Posaconazole against Clinical
Isolates of Dermatophytes
ABSTRACT
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TABLE 1.
In vitro activities of ITC and PCZ against
dermatophytes
To our knowledge, this is the first study in which the in vitro activity of the new antifungal agent PCZ against clinical isolates of dermatophytes has been investigated. Its activity was compared with that of ITC, a triazole whose activity against this group of fungi is well recognized. Our data showed that this new molecule appears to be as active in vitro as ITC against dermatophytes commonly encountered in clinical practice. In addition, PCZ showed a higher fungicidal activity than that of ITC against isolates belonging to the genus Microsporum. It must be noted that the correlation between in vitro results and clinical outcomes of cases of dermatophytosis is still to be established, and we therefore caution against extrapolating these results to clinical situations without additional testing of a larger sample of dermatophytes. Nevertheless, based on our study, PCZ merits further investigation as a potentially useful agent for the treatment of dermatophytosis.
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ACKNOWLEDGMENTS |
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This work was supported in part by grants from the Ministero dell'Università e della Ricerca Scientifica e Tecnologica (Cofin) and from the Istituto Superiore di Sanità (III AIDS project, contract no. 50C.29), Rome, Italy.
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FOOTNOTES |
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* Corresponding author. Mailing address: Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Azienda Ospedaliera Umberto I°, Via Conca, 60020, Ancona, Italy. Phone: 39.71.5963467. Fax: 39.71.5963468. E-mail: cmalinf{at}popcsi.unian.it.
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Journal of Clinical Microbiology, November 2001, p. 4208-4209, Vol. 39, No. 11
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.11.4208-4209.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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