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JAC Advance Access published online on June 23, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh335
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received August 28, 2003
Revised May 18, 2004
Accepted May 25, 2004

Original article

Alternatives to amphotericin B for Candida rugosa infection

Steve Hernandez 1*, Gloria M. Gonzalez 2, Dora I. McCarthy 3, Arnaldo Lopes Colombo 4, Laura K. Najvar 1, Rosie Bocanegera 1, John R. Graybill 1

1 Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
2 Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico
3 Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
4 Division of Infectious Diseases, Universidad Federal de São Paulo, São Paulo, Brazil

* To whom correspondence should be addressed. E-mail: Hernandezs{at}uthscsa.edu.


  Abstract

Objective: Amphotericin B failure is frequently seen in patients with candidaemia caused by Candida rugosa. We evaluated amphotericin B, fluconazole, posaconazole and voriconazole as alternative treatments against infection in mice with two isolates of C. rugosa.

Methods: Neutropenic mice were inoculated intravenously with C. rugosa. Amphotericin B, fluconazole, posaconazole and voriconazole were administered for 7 days after infection. Efficacy of the antifungal treatment was assessed by survival and tissue burden of C. rugosa.

Results: All of the four drugs significantly prolonged survival over controls. With both isolates, kidney counts were reduced significantly below controls for amphotericin B, fluconazole and posaconazole. However, voriconazole was less effective than the other antifungals.

Conclusion: Despite poor clinical response to amphotericin B, in vivo data indicate that amphotericin B increases organ clearance and survival over untreated controls. However, although voriconazole improved survival over controls, increased tissue clearance was not seen. This discrepancy may be caused by rapid clearance of voriconazole in mice. These studies suggest fluconazole, posaconazole or voriconazole may be useful alternatives to amphotericin B in therapy of C. rugosa infection.

Keywords: murine model; antifungals; C. rugosa.
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