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Antimicrobial Agents and Chemotherapy, January 2007, p. 73-77, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00969-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Posaconazole Prophylaxis in Experimental Systemic Zygomycosis{triangledown}

Francesco Barchiesi,1* Elisabetta Spreghini,1 Alfredo Santinelli,2 Annette W. Fothergill,4 Eleonora Pisa,2 Daniele Giannini,3 Michael G. Rinaldi,4,5 and Giorgio Scalise1

Istituto di Malattie Infettive e Medicina Pubblica,1 Istituto di Anatomia Patologica,2 Centro Gestione Presidenza Medicina e Chirurgia, Università Politecnica delle Marche, Ancona, Italy,3 Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas,4 Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, Texas5

Received 3 August 2006/ Returned for modification 5 September 2006/ Accepted 15 October 2006

Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days –2 and –1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues. AMB significantly prolonged the survival of mice infected with all isolates. POS significantly prolonged the survival of mice infected with zygomycetes. Cultured organs from mice infected with R. oryzae were all positive, while treated mice challenged with A. corymbifera generally showed lower percentages of infected organs compared with the percentages for the controls. Zygomycete isolates established an active infection (the presence of hyphae) in the brains and the kidneys of all controls. In mice challenged with R. oryzae, both antifungal drugs were effective at reducing the number and the size of infection foci in the kidneys. Only AMB reduced the numbers, but not the sizes, of infection foci in the brain. Finally, both drugs significantly reduced the numbers and the sizes of infection foci in both tissues of mice infected with A. corymbifera. Our data suggest that prophylaxis with POS has some potential to prevent zygomycosis.

* Corresponding author. Mailing address: Istituto di Malattie Infettive e Medicina Pubblica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-Lancisi-Salesi, Via Conca, Torrette, Ancona 60020, Italy. Phone: 39 0715963467. Fax: 39 0715963468. E-mail: l.infettive{at}ao-umbertoprimo.marche.it.

{triangledown} Published ahead of print on 23 October 2006.

Antimicrobial Agents and Chemotherapy, January 2007, p. 73-77, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00969-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Rodriguez, M. M., Serena, C., Marine, M., Pastor, F. J., Guarro, J. (2008). Posaconazole Combined with Amphotericin B, an Effective Therapy for a Murine Disseminated Infection Caused by Rhizopus oryzae. Antimicrob. Agents Chemother. 52: 3786-3788 [Abstract] [Full Text]  
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