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 Petraitis, V.
Right arrow Articles by Walsh, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petraitis, V.
Right arrow Articles by Walsh, T. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2002, p. 1857-1869, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1857-1869.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Comparative Antifungal Activities and Plasma Pharmacokinetics of Micafungin (FK463) against Disseminated Candidiasis and Invasive Pulmonary Aspergillosis in Persistently Neutropenic Rabbits

Vidmantas Petraitis,1 Ruta Petraitiene,1 Andreas H. Groll,1 Kristin Roussillon,1 Melissa Hemmings,1 Caron A. Lyman,1 Tin Sein,1 John Bacher,2 Ihor Bekersky,3 and Thomas J. Walsh1*

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 Warren Grant Magnuson Clinical Center and Surgery Service, Veterinary Resources Program, Office of Research Services, National Institutes of Health, Bethesda, Maryland,2 Fujisawa Healthcare, Inc., Deerfield, Illinois3

Received 6 August 2001/ Returned for modification 25 November 2001/ Accepted 25 February 2002

Micafungin (FK463) is an echinocandin that demonstrates potent in vitro antifungal activities against Candida and Aspergillus species. However, little is known about its comparative antifungal activities in persistently neutropenic hosts. We therefore investigated the plasma micafungin pharmacokinetics and antifungal activities of micafungin against experimental disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. The groups with disseminated candidiasis studied consisted of untreated controls (UCs); rabbits treated with desoxycholate amphotericin B (DAMB) at 1 mg/kg of body weight/day; or rabbits treated with micafungin at 0.25, 0.5, 1, and 2 mg/kg/day intravenously. Compared with the UCs, rabbits treated with micafungin or DAMB showed significant dosage-dependent clearance of Candida albicans from the liver, spleen, kidney, brain, eye, lung, and vena cava. These in vivo findings correlated with the results of in vitro time-kill assays that demonstrated that micafungin has concentration-dependent fungicidal activity. The groups with invasive pulmonary aspergillosis studied consisted of UCs; rabbits treated with DAMB; rabbits treated with liposomal amphotericin B (LAMB) at 5 mg/kg/day; and rabbits treated with micafungin at 0.5, 1, and 2 mg/kg/day. In comparison to the significant micafungin dosage-dependent reduction of the residual burden (in log CFU per gram) of C. albicans in tissue, micafungin-treated rabbits with invasive pulmonary aspergillosis had no reduction in the concentration of Aspergillus fumigatus in tissue. DAMB and LAMB significantly reduced the burdens of C. albicans and A. fumigatus in tissues (P < 0.01). Persistent galactomannan antigenemia in micafungin-treated rabbits correlated with the presence of an elevated burden of A. fumigatus in pulmonary tissue. By comparison, DAMB- and LAMB-treated animals had significantly reduced circulating galactomannan antigen levels. Despite a lack of clearance of A. fumigatus from the lungs, there was a significant improvement in the rate of survival (P < 0.001) and a reduction in the level of pulmonary infarction (P < 0.05) in micafungin-treated rabbits. In summary, micafungin demonstrated concentration-dependent and dosage-dependent clearance of C. albicans from persistently neutropenic rabbits with disseminated candidiasis but not of A. fumigatus from persistently neutropenic rabbits with invasive pulmonary aspergillosis.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Rm. 13N240, Center Dr., Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: walsht{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, June 2002, p. 1857-1869, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1857-1869.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nagasaki, Y., Eriguchi, Y., Uchida, Y., Miyake, N., Maehara, Y., Kadowaki, M., Harada, M., Akashi, K., Shimono, N. (2009). Combination therapy with micafungin and amphotericin B for invasive pulmonary aspergillosis in an immunocompromised mouse model. J Antimicrob Chemother 0: dkp175v1-dkp175 [Abstract] [Full Text]  
  • Petraitiene, R., Petraitis, V., Hope, W. W., Mickiene, D., Kelaher, A. M., Murray, H. A., Mya-San, C., Hughes, J. E., Cotton, M. P., Bacher, J., Walsh, T. J. (2008). Cerebrospinal Fluid and Plasma (1->3)-{beta}-D-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis. Antimicrob. Agents Chemother. 52: 4121-4129 [Abstract] [Full Text]  
  • Andes, D. R., Diekema, D. J., Pfaller, M. A., Marchillo, K., Bohrmueller, J. (2008). In Vivo Pharmacodynamic Target Investigation for Micafungin against Candida albicans and C. glabrata in a Neutropenic Murine Candidiasis Model. Antimicrob. Agents Chemother. 52: 3497-3503 [Abstract] [Full Text]  
  • Andes, D., Diekema, D. J., Pfaller, M. A., Prince, R. A., Marchillo, K., Ashbeck, J., Hou, J. (2008). In Vivo Pharmacodynamic Characterization of Anidulafungin in a Neutropenic Murine Candidiasis Model. Antimicrob. Agents Chemother. 52: 539-550 [Abstract] [Full Text]  
  • Keirns, J., Sawamoto, T., Holum, M., Buell, D., Wisemandle, W., Alak, A. (2007). Steady-State Pharmacokinetics of Micafungin and Voriconazole after Separate and Concomitant Dosing in Healthy Adults. Antimicrob. Agents Chemother. 51: 787-790 [Abstract] [Full Text]  
  • Francesconi, A., Kasai, M., Petraitiene, R., Petraitis, V., Kelaher, A. M., Schaufele, R., Hope, W. W., Shea, Y. R., Bacher, J., Walsh, T. J. (2006). Characterization and Comparison of Galactomannan Enzyme Immunoassay and Quantitative Real-Time PCR Assay for Detection of Aspergillus fumigatus in Bronchoalveolar Lavage Fluid from Experimental Invasive Pulmonary Aspergillosis.. J. Clin. Microbiol. 44: 2475-2480 [Abstract] [Full Text]  
  • Messer, S. A., Diekema, D. J., Boyken, L., Tendolkar, S., Hollis, R. J., Pfaller, M. A. (2006). Activities of Micafungin against 315 Invasive Clinical Isolates of Fluconazole-Resistant Candida spp.. J. Clin. Microbiol. 44: 324-326 [Abstract] [Full Text]  
  • Kasai, M., Francesconi, A., Petraitiene, R., Petraitis, V., Kelaher, A. M., Kim, H.-s., Meletiadis, J., Sein, T., Bacher, J., Walsh, T. J. (2006). Use of Quantitative Real-Time PCR To Study the Kinetics of Extracellular DNA Released from Candida albicans, with Implications for Diagnosis of Invasive Candidiasis. J. Clin. Microbiol. 44: 143-150 [Abstract] [Full Text]  
  • Scotter, J. M., Chambers, S. T. (2005). Comparison of Galactomannan Detection, PCR-Enzyme-Linked Immunosorbent Assay, and Real-Time PCR for Diagnosis of Invasive Aspergillosis in a Neutropenic Rat Model and Effect of Caspofungin Acetate. CVI 12: 1322-1327 [Abstract] [Full Text]  
  • Seibel, N. L., Schwartz, C., Arrieta, A., Flynn, P., Shad, A., Albano, E., Keirns, J., Lau, W. M., Facklam, D. P., Buell, D. N., Walsh, T. J. (2005). Safety, Tolerability, and Pharmacokinetics of Micafungin (FK463) in Febrile Neutropenic Pediatric Patients. Antimicrob. Agents Chemother. 49: 3317-3324 [Abstract] [Full Text]  
  • Petraitiene, R., Petraitis, V., Kelaher, A. M., Sarafandi, A. A., Mickiene, D., Groll, A. H., Sein, T., Bacher, J., Walsh, T. J. (2005). Efficacy, Plasma Pharmacokinetics, and Safety of Icofungipen, an Inhibitor of Candida Isoleucyl-tRNA Synthetase, in Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits. Antimicrob. Agents Chemother. 49: 2084-2092 [Abstract] [Full Text]  
  • Hiemenz, J., Cagnoni, P., Simpson, D., Devine, S., Chao, N., Keirns, J., Lau, W., Facklam, D., Buell, D. (2005). Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant. Antimicrob. Agents Chemother. 49: 1331-1336 [Abstract] [Full Text]  
  • Carver, P. L (2004). Micafungin. The Annals of Pharmacotherapy 38: 1707-1721 [Abstract] [Full Text]  
  • Pfaller, M. A., Sheehan, D. J., Rex, J. H. (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 [Abstract] [Full Text]  
  • Imhof, A., Balajee, S. A., Marr, K. A. (2003). New Methods To Assess Susceptibilities of Aspergillus Isolates to Caspofungin. J. Clin. Microbiol. 41: 5683-5688 [Abstract] [Full Text]  
  • Graybill, J. R., Bocanegra, R., Gonzalez, G. M., Najvar, L. K. (2003). Combination antifungal therapy of murine aspergillosis: liposomal amphotericin B and micafungin. J Antimicrob Chemother 52: 656-662 [Abstract] [Full Text]  
  • Andes, D. (2003). In Vivo Pharmacodynamics of Antifungal Drugs in Treatment of Candidiasis. Antimicrob. Agents Chemother. 47: 1179-1186 [Full Text]  
  • Warn, P. A., Morrissey, G., Morrissey, J., Denning, D. W. (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 [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»