Effect of Delay Exposure and Supra/Sub-MIC Concentrations of Amphotericin B to Aspergillus Conidial, Hyphal and Mycelial Growth

Ref ID: 18676

Author:

K. Krompa, MD – PhD student, N. Siafakas, PhD – Lecturer, L. Zerva, MD – Professor, J. Meletiadis, PhD – Lecturer;

Author address:

Attikon Univ. Gen. Hosp., Athens, Greece.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Delay administration and suboptimal exposure of antifungal drugs may be detrimental for Aspergillus infections. Therefore, we studied the pharmacodynamic characteristics of supra- and sub-MIC concentrations of amphotericin B (AMB) administered with and without delay against different stages of Aspergillus growth. Methods: Inocula of 104 CFU/ml from each of 5 clinical A. flavus, A. fumigatus, A. terreus isolates with CLSI MIC AMB 0.25-1 mg/l were prepared in 200μl RPMI1640+MOPS and incubated inside the wells of a 96-well flatbottom microplate at 37oC for 96h. AMB was added into corresponding wells at final concentrations of 0.25x, 1x, and 4x MIC after 0h, 24h and 48h of incubation in order to study the effect of AMB against conidia, hyphae, and mycelia, respectively. The turbidity of each well was monitored continuously by measuring the optical density (OD) at 630nm every 15min with a spectrophotometer. Growth curves were constructed and fungal growth before and after addition of the drugs was compared at each time point and for each concentration. After drug addition, % growth reduction calculated as 100% x (ODafter-ODbefore)/ODbefore (where ODafter and ODbefore were the ODs after and before drug addition, respectively) and the period of complete inhibition (PCI) after drug addition were determined. Results: When 4x, 1x, 0,25x MIC of AMB was added to Aspergillus conidia, PCI was > 96h, 38-83h and 27-48h, respectively for all species. When 4x, 1x, 0.25x MIC of AMB was added to Aspergillus hyphae, growth reduction was 13-16%, 10.2-10.4% and 0% and PCI was 58-72h, 31-47h and 10.55-25.8h, respectively for all species. When 4x, 1x, 0.25x MIC of AMB was added to Aspergillus mycelia, reduction of growth was 15-23.6%, 10,8-16.4% and 1.6-6% and PCI was 31-48h, 14-33h, and 5-14h, respectively for all species except A. terreus for which the PCI was <5h. Conclusions: AMB completely inhibited Aspergillus conidia at 4x MIC but not 1x and 0.25xMIC since regrowth was observed after 27-82h. The effect of AMB was diminished against Aspergillus hyphae and mycelia particularly for A. terreus mycelia where regrowth was observed immediately after drug addition. No growth reduction was observed at sub-MIC concentrations.

Abstract Number: A-1940

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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