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Antimicrobial Agents and Chemotherapy, August 2005, p. 3341-3346, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3341-3346.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Relationship between In Vitro Activities of Amphotericin B and Flucytosine and pH for Clinical Yeast and Mold Isolates

D. T. A. te Dorsthorst,1,2,3 P. E. Verweij,2,3 J. F. G. M. Meis,1 and J. W. Mouton1*

Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital,1 Department of Medical Microbiology, Radboud University Nijmegen Medical Center,2 Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands3

Received 7 January 2005/ Returned for modification 28 March 2005/ Accepted 15 May 2005

In this study, we investigated the pH dependency of the in vitro activities of amphotericin B (AMB) and flucytosine (5FC) against Candida spp., Cryptococcus neoformans, Aspergillus fumigatus, Rhizopus spp., and Scedosporium prolificans in RPMI 1640 buffered with citrate buffer (pH 4.0, 5.0, 5.4, and 6.0), citrate-phosphate buffer (pH 5.4, 6.0, 6.4, and 7.0), and 3-[N-morpholino]propanesulfonic acid (MOPS) (pH 6.4, 7.0, 7.4, and 7.9). For 5FC, no significant differences were found between MICs obtained with the different buffers, while for AMB, significant differences were found. The MICs obtained with citrate-phosphate buffer were approximately 1 twofold-dilution step higher than the MICs obtained with MOPS. We demonstrated that the in vitro activities of AMB and 5FC against yeast and mold isolates were pH dependent. The in vitro activity of AMB decreased when the pH was lowered, while the in vitro activity of 5FC increased. The effect of the pH on the in vitro activities was dependent not only on the antifungal agent tested but also on the microorganism. For AMB, there was a nonlinear relationship (median r2, 0.864) for Candida spp., C. neoformans, A. fumigatus, and Rhizopus spp. over the pH range tested. The mean MICs ranged from 0.5 to 2.52 µg/ml at pH 7.0 and from 20.16 to 32 µg/ml at pH 5.0. For S. prolificans, there was no relationship. For 5FC, there was a linear relationship for Candida spp. (median r2, 0.767) and a nonlinear relationship for C. neoformans and A. fumigatus (median r2, 0.882) over the pH range tested. The mean MIC values ranged from 0.125 to 1,024 µg/ml at pH 7.0 and from 0.02 to 4 µg/ml at pH 5.0. For Rhizopus spp. and S. prolificans, the relationship could not be determined, since the MIC was >1,024 µg/ml over a pH range of 4.0 to 7.9.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ Nijmegen, The Netherlands. Phone: 31-(0)24-3657514. Fax: 31-(0)24-3657516. E-mail: mouton{at}cwz.nl.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3341-3346, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3341-3346.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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