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Antimicrobial Agents and Chemotherapy, September 2007, p. 3329-3337, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00345-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Fungicidal Activities of Amphotericin B and Voriconazole against Aspergillus Species Determined by Microbroth Methodology{triangledown}

Joseph Meletiadis,1 Charalampos Antachopoulos,1 Theodouli Stergiopoulou,1 Spyros Pournaras,2 Emmanuel Roilides,3 and Thomas J. Walsh1*

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland,1 Department of Clinical Microbiology, University of Thessalia, Larissa, Greece,2 Third Department of Pediatrics, Aristotle University, Hippokration Hospital, Thessaloniki, Greece3

Received 14 March 2007/ Returned for modification 12 May 2007/ Accepted 11 June 2007

Antifungal agents may differ in their fungicidal activities against Aspergillus spp. In order to compare the fungicidal activities of voriconazole and amphotericin B against 40 isolates of Aspergillus fumigatus, A. flavus, and A. terreus, we developed a new microbroth colorimetric method for assessing fungicidal activities and determining minimal fungicidal concentrations (MFCs). This methodology follows the antifungal susceptibility testing reference method M-38A for MIC determination. After drug removal and addition of fresh medium, growth of viable conidia adhering to the bottoms of the microtitration wells was assessed by a colorimetric assay of metabolic activity after 24 h of incubation. The new method was faster (six times), reproducible (92 to 97%), and in agreement with culture-based MFCs (91 to 100%). Differential fungicidal activities of voriconazole and amphotericin B were found among the three Aspergillus species, with A. fumigatus and A. flavus having the lowest (1 and 2 mg/liter, respectively) and A. terreus the highest (>16 mg/liter) median amphotericin B MFCs; A. flavus had a lower median voriconazole MFC (4 mg/liter) than the other species (>8 mg/liter; P < 0.05). Amphotericin B was fungicidal (MFC/MIC ≤ 4) against all A. fumigatus and A. flavus isolates but no A. terreus isolates, whereas voriconazole was fungicidal against 82% of A. flavus isolates and fungistatic (MFC/MIC > 4) against 94% of A. fumigatus and 84% of A. terreus isolates. The new methodology revealed a concentration-dependent sigmoid pattern of fungicidal effects, indicating that fungicidal activity is not an all-or-nothing phenomenon and that some degree of fungicidal action can be found even for agents considered fungistatic based on the MFC/MIC ratio.

* Corresponding author. Mailing address: Pediatric Oncology Branch, National Cancer Institute, 10 Center Drive, Bldg. 10/Rm. 1-5750, Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 480-2308. E-mail: walsht{at}mail.nih.gov

{triangledown} Published ahead of print on 18 June 2007.

Antimicrobial Agents and Chemotherapy, September 2007, p. 3329-3337, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00345-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gautam, P., Shankar, J., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., Basir, S. F., Sarma, P. U. (2008). Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B. Antimicrob. Agents Chemother. 52: 4220-4227 [Abstract] [Full Text]  


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