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Antimicrobial Agents and Chemotherapy, February 2001, p. 633-635, Vol. 45, No. 2
Fungus Testing Laboratory, Department of
Pathology, University of Texas Health Science Center at San
Antonio,1 and Audie L. Murphy Division,
South Texas Veterans Health Care System,3 San
Antonio, Texas 78229-3900, and Departamento de
Microbiología, Facultad de Medicina, Universidad
Autónoma de Nuevo León, Monterrey, Nuevo León,
México2
Received 21 August 2000/Returned for modification 3 October
2000/Accepted 20 November 2000
The in vitro activity of amphotericin B, fluconazole, flucytosine,
itraconazole, voriconazole, and posaconazole was evaluated against 44 clinical isolates of filamentous basidiomycetous fungi. No
statistically significant differences were noted between
Schizophyllum commune (n = 5),
Coprinus species (n = 8),
Bjerkandera adusta (n = 14), and sterile,
uncharacterized basidiomycetes (n = 17).
The spectrum of documented
infections reported for basidiomycetes, namely Schizophyllum
commune and Coprinus species, include endocarditis, meningitis, sinusitis, ulcerative lesions of the hard
palate, fungal ball of the lung, allergic bronchopulmonary conditions, bronchial mucoid impaction, and chronic respiratory disease. Mycoses have occurred in both immunocompetent and
immunocompromised hosts (1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 14,
15).
Although filamentous basidiomycetes fungi are being increasingly
recognized, their definitive identification is problematic, with many
isolates remaining sterile in culture (12).
In addition to the difficulty surrounding identification, assessment of
pathogenicity is equally uncertain. Despite these obstacles, clinicians
frequently request information regarding potential therapeutic
regimens. We therefore sought to determine the in vitro activity of
various approved and investigational antifungal compounds against this
group of fungi.
Testing was accomplished in a head-to-head format on 44 clinical
isolates submitted to the Fungus Testing Laboratory, Department of
Pathology, University of Texas Health Science Center at San Antonio.
Isolates tested and their presumptive identifications were as follows:
S. commune (n = 5), Coprinus
species (n = 8), Bjerkandera adusta
(n = 14), and sterile, uncharacterized basidiomycetes (n = 17). Strains are identified in Table
1. While the clinical significance of
each isolate was difficult to determine, several isolates were
recovered from profoundly immunocompromised patients whose underlying
conditions support invasion by normally nonvirulent fungi.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.2.633-635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
In Vitro Activities of Approved and Investigational Antifungal
Agents against 44 Clinical Isolates of Basidiomycetous Fungi
ABSTRACT
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TABLE 1.
Basidiomycete isolates used in this study
Isolates were maintained in water suspensions at room temperature until
testing. The antifungal agents used were provided as standard powders
of known potency. Serial twofold dilutions of each antifungal agent
were prepared to give the following final drug concentrations: 0.03 to
16 µg/ml for amphotericin B (AMB); 0.125 to 64 µg/ml for
fluconazole (FLC), voriconazole (VRC), and flucytosine (5FC); and 0.015 to 8 µg/ml for itraconazole (ITC) and posaconazole (PSC). A
0.1-ml aliquot of the twofold serial dilutions was dispensed into a
sterile plastic snap-cap tube (12 by 75 mm) that was then maintained at
70°C until needed. AMB was tested in antibiotic medium 3 (Difco,
Detroit, Mich.), and other agents were tested in RPMI 1640 (Angus,
Niagara Falls, N.Y.). Isolates were tested using the National Committee
for Clinical Laboratory Standards macrobroth dilution method M38-P
(reference method for broth dilution antifungal susceptibility testing
of conidium-forming filamentous fungi, proposed standard). Briefly, isolates were grown on potato flakes agar prepared in-house
(8) for 7 days at 30°C. Inocula were standardized
spectrophotometrically to 80% transmittance at 530 nm. Suspensions
were further diluted 1:10 in media for a final concentration of
approximately 1 × 104 CFU/ml. Previously prepared
aliquots of frozen drugs containing 0.1 ml of drug were allowed to thaw
and were inoculated with 0.9 ml of the suspension. Tubes were incubated
at room temperature, and the 72- to 96-h MICs were defined as the drug
concentration of the first tube that yielded a score of 0 (optically
clear) for AMB and a score of 2 (reduction in turbidity of 
80%
compared to the drug-free control tube) for FLC, VRC, 5FC, ITC, and
PSC. The University of Texas Health Science Center
Paecilomyces control strain 90-459 was included with all testing.
Table 2 summarizes the in vitro
antifungal susceptibility data for the 44 strains tested. The 96-hour
geometric mean, range, and MICs inhibiting 50 and 90% of the isolates
for AMB, ITC, VRC, and PSC were consistently low. For 5FC and FLC, the
values were somewhat higher although still within normally achievable
concentrations in serum. The data were evaluated by the Sidak multiple
comparisons t test with a one-way analysis of variance.
Results indicated no statistically significant differences between the
organisms evaluated.
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Previous in vitro susceptibility data for basidiomycetes have been
limited to small numbers of strains or individual isolates. The
S. commune isolate described by Rihs et al. (7)
with dissemination to the brain required MICs of <0.03 and 8 µg/ml for AMB and FLC, respectively. ITC could not be tested due
to failure of the isolate to grow in the test medium. Gené et al.
(2) studied a total of 12 environmental and clinical
strains of Coprinus cinereus, Hormographiella
aspergillata, and Hormographiella verticillata. All
strains were susceptible to miconazole, ITC, and ketoconazole with MICs
ranging from 0.6 to 5.0 µg/ml, 0.07 to 0.6 µg/ml, and 0.2 to 1.6 µg/ml, respectively. They were resistant to fluconazole (20 to >80
µg/ml) and 5FC (322 to >322 µg/ml), while their susceptibility to
AMB was variable (
0.07 to 4.6 µg/ml). All strains of H. verticillata appeared susceptible to AMB; however, four of seven
strains of C. cinereus displayed resistance (2.3 to 4.6 µg/ml). Verweij et al. (15) reported a case of fatal
pneumonia due to H. aspergillata in a patient receiving
intensive cytotoxic treatment. The results of in vitro susceptibility
testing by agar dilution and broth macrodilution of the isolate showed
low MICs for AMB and high MICs for ITC (8 to 32 mg/liter), suggesting
in vitro resistance to that agent. The MIC for FLC was also high, at
>64 mg/liter. No correlation between in vitro susceptibility data and
therapeutic response was noted, as AMB-associated toxicity required
changing to an ITC regimen, with the patient expiring 9 days later.
In vitro susceptibility data for approved and investigational antifungal agents are presented. Additional studies may further elucidate the correlation between in vitro data and clinical efficacy in mycoses caused by basidiomycetous fungi.
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FOOTNOTES |
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* Corresponding author. Mailing address: Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. Phone: (210) 567-4131. Fax: (210) 567-4076. E-mail: gonzalezg{at}uthscsa.edu.
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Antimicrobial Agents and Chemotherapy, February 2001, p. 633-635, Vol. 45, No. 2
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.2.633-635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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