[en] 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.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Antachopoulos, C., J. Meletiadis, T. Sein, E. Roilides, and T. J. Walsh. 2006. Use of high inoculum for early metabolic signalling and rapid susceptibility testing of Aspergillus species. J. Antimicrob. Chemother. 59:230-237.
Chandrasekar, P. H., J. Cutright, and E. Manavathu. 2000. Efficacy of voriconazole against invasive pulmonary aspergillosis in a guinea-pig model. J. Antimicrob. Chemother. 45:673-676.
Clancy, C. J., and M. H. Nguyen. 1998. In vitro efficacy and fungicidal activity of voriconazole against Aspergillus and Fusarium species. Eur. J. Clin. Microbiol. Infect. Dis. 17:573-575.
Clemons, K. V., M. Espiritu, R. Parmar, and D. A. Stevens. 2005. Comparative efficacies of conventional amphotericin B, liposomal amphotericin B (AmBisome), caspofungin, micafungin, and voriconazole alone and in combination against experimental murine central nervous system aspergillosis. Antimicrob. Agents Chemother. 49:4867-4875.
Espinel-Ingroff, A. 2001. Germinated and nongerminated conidial suspensions for testing of susceptibilities of Aspergillus spp. to amphotericin B, itraconazole, posaconazole, ravuconazole, and voriconazole. Antimicrob. Agents Chemother. 45:605-607.
Espinel-Ingroff, A. 2001. In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J. Clin. Microbiol. 39:954-958.
Espinel-Ingroff, A., V. Chaturvedi, A. Fothergill, and M. G. Rinaldi. 2002. Optimal testing conditions for determining MICs and minimum fungicidal concentrations of new and established antifungal agents for uncommon molds: NCCLS collaborative study. J. Clin. Microbiol. 40:3776-3781.
Espinel-Ingroff, A., A. Fothergill, M. Ghannoum, E. Manavathu, L. Ostrosky-Zeichner, M. Pfaller, M. Rinaldi, W. Schell, and T. Walsh. 2005. Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole. J. Clin. Microbiol. 43:5243-5246.
Espinel-Ingroff, A., A. Fothergill, J. Peter, M. G. Rinaldi, and T. J. Walsh. 2002. Testing conditions for determination of minimum fungicidal concentrations of new and established antifungal agents for Aspergillus spp.: NCCLS collaborative study. J. Clin. Microbiol. 40:3204-3208.
George, D., P. Miniter, and V. T. Andriole. 1996. Efficacy of UK-109496, a new azole antifungal agent, in an experimental model of invasive aspergillosis. Antimicrob. Agents Chemother. 40:86-91.
Johnson, E. M., A. Szekely, and D. W. Warnock. 1998. In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi. J. Antimicrob. Chemother. 42:741-745.
Kirkpatrick, W. R., R. K. McAtee, A. W. Fothergill, M. G. Rinaldi, and T. F. Patterson. 2000. Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis. Antimicrob. Agents Chemother. 44:2865-2868.
Manavathu, E. K., J. L. Cutright, and P. H. Chandrasekar. 1998. Organism-dependent fungicidal activities of azoles. Antimicrob. Agents Chemother. 42:3018-3021.
Meletiadis, J., J. W. Mouton, J. F. Meis, B. A. Bouman, J. P. Donnelly, and P. E. Verweij. 2001. Colorimetric assay for antifungal susceptibility testing of Aspergillus species. J. Clin. Microbiol. 39:3402-3408.
Motulsky, H. 2003. Prism 4 statistics guide - statistical analyses for laboratory and clinical researchers, p. 122-126. GraphPad Software Inc., San Diego, CA.
Motulsky, H., and A. Christopoulos. 2003. Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fitting. GraphPad Software Inc., San Diego, CA.
Murphy, M., E. M. Bernard, T. Ishimaru, and D. Armstrong. 1997. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis. Antimicrob. Agents Chemother. 41:696-698.
Odds, F. C., F. Van Gerven, A. Espinel-Ingroff, M. S. Bartlett, M. A. Ghannoum, M. V. Lancaster, M. A. Pfaller, J. H. Rex, M. G. Rinaldi, and T. J. Walsh. 1998. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob. Agents Chemother. 42:282-288.
Patterson, T. F., W. R. Kirkpatrick, M. White, J. W. Hiemenz, J. R. Wingard, B. Dupont, M. G. Rinaldi, D. A. Stevens, J. R. Graybill, et al. 2000. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. Medicine (Baltimore) 79:250-260.
Pfaller, M. A., D. J. Sheehan, and J. H. Rex. 2004. Determination of fungicidal activities against yeasts and molds: lessons learned from bactericidal testing and the need for standardization. Clin. Microbiol. Rev. 17:268-280.
Ramani, R., M. Gangwar, and V. Chaturvedi. 2003. Flow cytometry antifungal susceptibility testing of Aspergillus fumigatus and comparison of mode of action of voriconazole vis-a-vis amphotericin B and itraconazole. Antimicrob. Agents Chemother. 47:3627-3629.
Rodriguez-Tudela, J. L., E. Chryssanthou, E. Petrikkou, J. Mosquera, D. W. Denning, and M. Cuenca-Estrella. 2003. Interlaboratory evaluation of hematocytometer method of inoculum preparation for testing antifungal susceptibilities of filamentous fungi. J. Clin. Microbiol. 41:5236-5237.
Sutton, D. A., S. E. Sanche, S. G. Revankar, A. W. Fothergill, and M. G. Rinaldi. 1999. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J. Clin. Microbiol. 37:2343-2345.
Walsh, T. J., V. Petraitis, R. Petraitiene, A. Field-Ridley, D. Sutton, M. Ghannoum, T. Sein, R. Schaufele, J. Peter, J. Bacher, H. Casler, D. Armstrong, A. Espinel-Ingroff, M. G. Rinaldi, and C. A. Lyman. 2003. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J. Infect. Dis. 188:305-319.
Warn, P. A., G. Morrissey, J. Morrissey, and D. W. Denning. 2003. Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B. J. Antimicrob. Chemother. 51:913-919.
Warn, P. A., A. Sharp, and D. W. Denning. 2006. In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp. J. Antimicrob. Chemother. 57:135-138.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
