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JAC Advance Access originally published online on May 29, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 65-70
© 2003 The British Society for Antimicrobial Chemotherapy

Evaluation of the post-antifungal effect (PAFE) of amphotericin B and nystatin against 30 zygomycetes using two different media

Roxana G. Vitale1,2, Jacques F. G. M. Meis3, Johan W. Mouton3 and Paul E. Verweij1,2,*

1 Department of Medical Microbiology, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen; 2 Nijmegen University Center for Infectious Diseases, Nijmegen; 3 Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

Received 13 December 2002; returned 9 March 2003; revised 14 April 2003; accepted 14 April 2003

The post-antifungal effect (PAFE) of amphotericin B and nystatin against 30 clinical zygomycetes was evaluated using two different media. PAFE is a suppression of fungal growth after limited drug exposure. The MICs of both drugs were determined using NCCLS M38-P guidelines. A spectrophotometric method was used to determine PAFE in vitro. Spores were exposed to amphotericin B and nystatin in RPMI-1640 or AM3 at concentrations of 4 x and 1 x MIC for 4 h for Absidia sp. and at 1 x and 0.5 x MIC for 1 h for the other strains. Drugs were eliminated by washing. Exposed and control spores were cultured in microtitre wells and incubated for 48 h. PAFE was calculated as T – C ({Delta}t) between the control and the exposure fungi. The first increase in optical density (OD0) was used to calculate PAFE and was considered significant when the value of the lower 95%CI of the exposed strain was greater than the upper 95%CI of the control. MIC ranges in RPMI-1640 were: 0.06–4 mg/L for amphotericin B and 0.5–8 mg/L for nystatin; MIC ranges in AM3 were: 0.06–2 mg/L for amphotericin B and 0.5–4 mg/L for nystatin. Killing was not observed at the concentration and exposure time used. In RPMI-1640, for amphotericin B the rank order for PAFE was Absidia corymbifera (5.6 h) > Rhizopus oryzae (5.2 h) > Mucor spp. (3.5 h) > Rhizopus microsporus (3 h), and for nystatin the rank order was Mucor spp. (5.8 h) > R. oryzae (3.3 h) > A. corymbifera (2.9 h) > R. microsporus (1.7 h). PAFE was not induced in Rhizomucor spp. PAFE was dependent on drug concentration.

Keywords: PAFE, zygomycetes, amphotericin B, nystatin

* Corresponding author. Tel: +31-24-361-4356; Fax: +31-24-354-0216; E-mail: p.verweij{at}mmb.umcn.nl


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