This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cacciapuoti, A.
Right arrow Articles by Hare, R. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cacciapuoti, A.
Right arrow Articles by Hare, R. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2000, p. 2017-2022, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

In Vitro and In Vivo Activities of SCH 56592 (Posaconazole), a New Triazole Antifungal Agent, against Aspergillus and Candida

Anthony Cacciapuoti,* David Loebenberg, Erik Corcoran,dagger Fred Menzel Jr., Eugene L. Moss Jr., Christine Norris, Monika Michalski, Kimberly Raynor, Judith Halpern, Cara Mendrick, Brian Arnold, Barry Antonacci, Raulo Parmegiani, Taisa Yarosh-Tomaine, George H. Miller,dagger and Roberta S. Hare

Schering-Plough Research Institute, Kenilworth, New Jersey 07033-1300

Received 18 January 2000/Returned for modification 16 February 2000/Accepted 28 April 2000

SCH 56592 (posaconazole), a new triazole antifungal agent, was tested in vitro, and its activity was compared to that of itraconazole against 39 Aspergillus strains and to that of fluconazole against 275 Candida and 9 Cryptococcus strains. The SCH 56592 MICs for Aspergillus ranged from <= 0.002 to 0.5 µg/ml, and those of itraconazole ranged from <= 0.008 to 1 µg/ml. The SCH 56592 MICs for Candida and Cryptococcus strains ranged from <= 0.004 to 16 µg/ml, and those of fluconazole ranged from <= 0.062 to >64 µg/ml. SCH 56592 showed excellent activity against Aspergillus fumigatus and Aspergillus flavus in a pulmonary mouse infection model. When administered therapeutically, the 50% protective doses (PD50s) of SCH 56592 ranged from 3.6 to 29.9 mg/kg of body weight, while the PD50s of SCH 56592 administered prophylactically ranged from 0.9 to 9.0 mg/kg; itraconazole administered prophylactically was ineffective (PD50s, >75 mg/kg). SCH 56592 was also very efficacious against fluconazole-susceptible, -susceptible dose-dependent, or -resistant Candida albicans strains in immunocompetent or immunocompromised mouse models of systemic infection. The PD50s of SCH 56592 administered therapeutically ranged from 0.04 to 15.6 mg/kg, while the PD50s of SCH 56592 administered prophylactically ranged from 1.5 to 19.4 mg/kg. SCH 56592 has excellent potential for therapy against serious Aspergillus or Candida infections.

* Corresponding author. Mailing address: Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033-1300. Phone: (908) 740-3139. Fax: (908) 740-3918. E-mail: anthony.cacciapuoti{at}spcorp.com.

dagger Present address: Research & Development, Microcide Pharmaceuticals Inc., Mountain View, CA 94043.

Antimicrobial Agents and Chemotherapy, August 2000, p. 2017-2022, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Spreghini, E., Maida, C. M., Tomassetti, S., Orlando, F., Giannini, D., Milici, M. E., Scalise, G., Barchiesi, F. (2008). Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole. Antimicrob. Agents Chemother. 52: 1929-1933 [Abstract] [Full Text]  
  • Spreghini, E., Maida, C. M., Milici, M. E., Scalise, G., Barchiesi, F. (2008). Posaconazole Activity against Candida glabrata after Exposure to Caspofungin or Amphotericin B. Antimicrob. Agents Chemother. 52: 513-517 [Abstract] [Full Text]  
  • Ullmann, A. J., Krammes, E., Sommer, S., Buschmann, I., Jahn-Muehl, B., Cacciapuoti, A., Schmitt, H.-J. (2007). Efficacy of posaconazole and amphotericin B in experimental invasive pulmonary aspergillosis in dexamethasone immunosuppressed rats. J Antimicrob Chemother 60: 1080-1084 [Abstract] [Full Text]  
  • Perkhofer, S., Lugger, H., Dierich, M. P., Lass-Florl, C. (2007). Posaconazole Enhances the Activity of Amphotericin B against Aspergillus Hyphae In Vitro. Antimicrob. Agents Chemother. 51: 791-793 [Abstract] [Full Text]  
  • Cacciapuoti, A., Halpern, J., Mendrick, C., Norris, C., Patel, R., Loebenberg, D. (2006). Interaction between Posaconazole and Caspofungin in Concomitant Treatment of Mice with Systemic Aspergillus Infection.. Antimicrob. Agents Chemother. 50: 2587-2590 [Abstract] [Full Text]  
  • Sabatelli, F., Patel, R., Mann, P. A., Mendrick, C. A., Norris, C. C., Hare, R., Loebenberg, D., Black, T. A., McNicholas, P. M. (2006). In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts.. Antimicrob. Agents Chemother. 50: 2009-2015 [Abstract] [Full Text]  
  • Cuenca-Estrella, M., Gomez-Lopez, A., Mellado, E., Buitrago, M. J., Monzon, A., Rodriguez-Tudela, J. L. (2006). Head-to-Head Comparison of the Activities of Currently Available Antifungal Agents against 3,378 Spanish Clinical Isolates of Yeasts and Filamentous Fungi. Antimicrob. Agents Chemother. 50: 917-921 [Abstract] [Full Text]  
  • Lopez-Oviedo, E., Aller, A. I., Martin, C., Castro, C., Ramirez, M., Peman, J. M., Canton, E., Almeida, C., Martin-Mazuelos, E. (2006). Evaluation of Disk Diffusion Method for Determining Posaconazole Susceptibility of Filamentous Fungi: Comparison with CLSI Broth Microdilution Method. Antimicrob. Agents Chemother. 50: 1108-1111 [Abstract] [Full Text]  
  • Carrillo-Munoz, A.-J., Quindos, G., Ruesga, M., Alonso, R., del Valle, O., Hernandez-Molina, J. M., McNicholas, P., Loebenberg, D., Santos, P. (2005). Antifungal activity of posaconazole compared with fluconazole and amphotericin B against yeasts from oropharyngeal candidiasis and other infections. J Antimicrob Chemother 55: 317-319 [Abstract] [Full Text]  
  • Cacciapuoti, A., Gurnani, M., Halpern, J., Norris, C., Patel, R., Loebenberg, D. (2005). Interaction between Posaconazole and Amphotericin B in Concomitant Treatment against Candida albicans In Vivo. Antimicrob. Agents Chemother. 49: 638-642 [Abstract] [Full Text]  
  • Munayyer, H. K., Mann, P. A., Chau, A. S., Yarosh-Tomaine, T., Greene, J. R., Hare, R. S., Heimark, L., Palermo, R. E., Loebenberg, D., McNicholas, P. M. (2004). Posaconazole Is a Potent Inhibitor of Sterol 14{alpha}-Demethylation in Yeasts and Molds. Antimicrob. Agents Chemother. 48: 3690-3696 [Abstract] [Full Text]  
  • Simitsopoulou, M., Gil-Lamaignere, C., Avramidis, N., Maloukou, A., Lekkas, S., Havlova, E., Kourounaki, L., Loebenberg, D., Roilides, E. (2004). Antifungal Activities of Posaconazole and Granulocyte-Macrophage Colony-Stimulating Factor Ex Vivo and in Mice with Disseminated Infection Due to Scedosporium prolificans. Antimicrob. Agents Chemother. 48: 3801-3805 [Abstract] [Full Text]  
  • Imai, J. K., Singh, G., Clemons, K. V., Stevens, D. A. (2004). Efficacy of Posaconazole in a Murine Model of Central Nervous System Aspergillosis. Antimicrob. Agents Chemother. 48: 4063-4066 [Abstract] [Full Text]  
  • Chau, A. S., Mendrick, C. A., Sabatelli, F. J., Loebenberg, D., McNicholas, P. M. (2004). Application of Real-Time Quantitative PCR to Molecular Analysis of Candida albicans Strains Exhibiting Reduced Susceptibility to Azoles. Antimicrob. Agents Chemother. 48: 2124-2131 [Abstract] [Full Text]  
  • Andes, D., Marchillo, K., Conklin, R., Krishna, G., Ezzet, F., Cacciapuoti, A., Loebenberg, D. (2004). Pharmacodynamics of a New Triazole, Posaconazole, in a Murine Model of Disseminated Candidiasis. Antimicrob. Agents Chemother. 48: 137-142 [Abstract] [Full Text]  
  • Li, X., Brown, N., Chau, A. S., Lopez-Ribot, J. L., Ruesga, M. T., Quindos, G., Mendrick, C. A., Hare, R. S., Loebenberg, D., DiDomenico, B., McNicholas, P. M. (2004). Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. J Antimicrob Chemother 53: 74-80 [Abstract] [Full Text]  
  • Dannaoui, E., Meis, J. F. G. M., Loebenberg, D., Verweij, P. E. (2003). Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis. Antimicrob. Agents Chemother. 47: 3647-3650 [Abstract] [Full Text]  
  • Courtney, R., Pai, S., Laughlin, M., Lim, J., Batra, V. (2003). Pharmacokinetics, Safety, and Tolerability of Oral Posaconazole Administered in Single and Multiple Doses in Healthy Adults. Antimicrob. Agents Chemother. 47: 2788-2795 [Abstract] [Full Text]  
  • Philippe, B., Ibrahim-Granet, O., Prevost, M. C., Gougerot-Pocidalo, M. A., Sanchez Perez, M., Van der Meeren, A., Latge, J. P. (2003). Killing of Aspergillus fumigatus by Alveolar Macrophages Is Mediated by Reactive Oxidant Intermediates. Infect. Immun. 71: 3034-3042 [Abstract] [Full Text]  
  • Mann, P. A., Parmegiani, R. M., Wei, S.-Q., Mendrick, C. A., Li, X., Loebenberg, D., DiDomenico, B., Hare, R. S., Walker, S. S., McNicholas, P. M. (2003). Mutations in Aspergillus fumigatus Resulting in Reduced Susceptibility to Posaconazole Appear To Be Restricted to a Single Amino Acid in the Cytochrome P450 14{alpha}-Demethylase. Antimicrob. Agents Chemother. 47: 577-581 [Abstract] [Full Text]  
  • Sponsel, W E, Graybill, J R, Nevarez, H L, Dang, D (2002). Ocular and systemic posaconazole(SCH-56592) treatment of invasive Fusarium solani keratitis and endophthalmitis. Br J Ophthalmol 86: 829-830 [Full Text]  
  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Jones, R. N., Diekema, D. J. (2002). In Vitro Activities of Ravuconazole and Voriconazole Compared with Those of Four Approved Systemic Antifungal Agents against 6,970 Clinical Isolates of Candida spp.. Antimicrob. Agents Chemother. 46: 1723-1727 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Jones, R. N. (2002). Antifungal Activities of Posaconazole, Ravuconazole, and Voriconazole Compared to Those of Itraconazole and Amphotericin B against 239 Clinical Isolates of Aspergillus spp. and Other Filamentous Fungi: Report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob. Agents Chemother. 46: 1032-1037 [Abstract] [Full Text]  
  • Chakinala, M. M., Kollef, M. H., Trulock, E. P. (2002). Critical Care Aspects of Lung Transplant Patients. J Intensive Care Med 17: 8-33 [Abstract]  
  • Pfaller, M. A., Messer, S. A., Mills, K., Bolmstrom, A., Jones, R. N. (2001). Evaluation of Etest Method for Determining Posaconazole MICs for 314 Clinical Isolates of Candida Species. J. Clin. Microbiol. 39: 3952-3954 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Jones, R. N. (2001). In Vitro Activities of Posaconazole (Sch 56592) Compared with Those of Itraconazole and Fluconazole against 3,685 Clinical Isolates of Candida spp. and Cryptococcus neoformans. Antimicrob. Agents Chemother. 45: 2862-2864 [Abstract] [Full Text]  
  • Brieland, J., Essig, D., Jackson, C., Frank, D., Loebenberg, D., Menzel, F., Arnold, B., DiDomenico, B., Hare, R. (2001). Comparison of Pathogenesis and Host Immune Responses to Candida glabrata and Candida albicans in Systemically Infected Immunocompetent Mice. Infect. Immun. 69: 5046-5055 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»