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Antimicrobial Agents and Chemotherapy, March 2007, p. 941-945, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00880-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Caspofungin in Combination with Amphotericin B against Candida parapsilosis{triangledown}

Francesco Barchiesi,1* Elisabetta Spreghini,1 Serena Tomassetti,1 Daniele Giannini,2 and Giorgio Scalise1

Istituto di Malattie Infettive e Medicina Pubblica,1 Centro di Gestione Presidenza Medicina e Chirurgia, Università Politecnica delle Marche, Ancona, Italy2

Received 17 July 2006/ Returned for modification 28 November 2006/ Accepted 30 November 2006

Candida parapsilosis has emerged as an important nosocomial pathogen. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of caspofungin (CAS) in combination with amphotericin B (AMB) against three clinical isolates of C. parapsilosis. Although there was a significant reduction of the MIC of one or both drugs used in combination, an indifferent interaction (fractional inhibitory concentration index greater than 0.50 and less than or equal to 4.0) was observed in 100% of cases. This finding was confirmed by killing curve studies. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were often significantly greater than those produced by each drug alone. Antagonism was never observed. In a murine model of systemic candidiasis, CAS at either 0.25 or 1 mg/kg/day combined with AMB at 1 mg/kg/day was significantly more effective than each single drug at reducing the colony counts in kidneys. Higher doses of the echinocandin (i.e., 5 and 10 mg/kg/day) combined with the polyene did not show any advantage over CAS alone. Overall, our study showed a positive interaction of CAS and AMB against C. parapsilosis.

* 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, 60020 Torrette, Ancona, Italy. Phone: 39 0715963467. Fax: 39 0715963468. E-mail: l.infettive{at}ao-umbertoprimo.marche.it.

{triangledown} Published ahead of print on 11 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 941-945, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00880-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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