Manavathu Elias K, Ramesh Mayur S, Baskaran Inthumathi, Ganesan Latha T, Chandrasekar Pranatharthi H
Division of Infectious Diseases, Department of Internal Medicine, 427 Lande Building, Wayne State University, 550 E. Canfield, Detroit, MI 48201, USA.
J Antimicrob Chemother. 2004 Feb;53(2):386-9. doi: 10.1093/jac/dkh066. Epub 2004 Jan 16.
To study the post-antifungal effect (PAFE) of antifungal drugs on Aspergillus fumigatus by a radiometric assay and compare the results with those obtained for Candida albicans.
A. fumigatus cultures pregrown for 48 h in 96-well microtitre plate were exposed to various concentrations of the antifungal drug for 2 h. The drug-treated mycelia were washed, incubated in RPMI 1640 containing (14)C-labelled amino acids and the accumulation of radioactivity in the mycelia at different time intervals was determined. The PAFE was determined by plotting the amount of radioactivity associated with the mycelia against post-treatment incubation time. The PAFE of antifungal drug on C. albicans was examined by determining the multiplication (cfu/mL) of drug-pretreated cells at different time intervals for 24 h in drug-free medium.
Amphotericin B produced a prolonged PAFE (7.5 +/- 0.70 h) against A. fumigatus whereas itraconazole (0.5 +/- 0.0 h), voriconazole (0.5 +/- 0.0 h), posaconazole (0.75 +/- 0.35 h), ravuconazole (0.38 +/- 0.17 h) and the echinocandins caspofungin (< or =0.5 h) and micafungin (< or =0.5 h) produced short PAFE. Short exposure (1 h) of C. albicans to low concentrations (0.125-1 mg/L) of amphotericin B (5.3 +/- 1.15 h), caspofungin (5.6 +/- 0.57 h) and micafungin (5 +/- 1.0 h) produced prolonged PAFE whereas the triazoles produced a short (< or =0.5 h) PAFE.
Determination of (14)C-labelled amino acid accumulation in antifungal drug-pretreated mycelia is a suitable method for studying PAFE in A. fumigatus. Antifungal drugs with fungicidal activity tend to possess longer PAFE compared to fungistatic drugs.
通过放射性测定法研究抗真菌药物对烟曲霉的抗真菌后效应（PAFE），并将结果与白色念珠菌的结果进行比较。
在96孔微量滴定板中预培养48小时的烟曲霉培养物暴露于不同浓度的抗真菌药物2小时。将经药物处理的菌丝体洗涤后，在含有（14）C标记氨基酸的RPMI 1640中孵育，并测定不同时间间隔菌丝体中放射性的积累。通过绘制与菌丝体相关的放射性量与处理后孵育时间的关系图来确定PAFE。通过在无药物培养基中在不同时间间隔24小时测定经药物预处理细胞的增殖（cfu/mL）来检查抗真菌药物对白色念珠菌的PAFE。
两性霉素B对烟曲霉产生了较长的PAFE（7.5±0.70小时），而伊曲康唑（0.5±0.0小时）、伏立康唑（0.5±0.0小时）、泊沙康唑（0.75±0.35小时）、雷夫康唑（0.38±0.17小时）以及棘白菌素类卡泊芬净（≤0.5小时）和米卡芬净（≤0.5小时）产生较短的PAFE。白色念珠菌短时间（1小时）暴露于低浓度（0.125 - 1mg/L）的两性霉素B（5.3±1.15小时）、卡泊芬净（5.6±0.57小时）和米卡芬净（5±1.0小时）产生较长的PAFE，而三唑类产生较短（≤0.5小时） 的PAFE。
测定抗真菌药物预处理菌丝体中（14）C标记氨基酸的积累是研究烟曲霉PAFE的合适方法。与抑菌药物相比具有杀菌活性 的抗真菌药物往往具有更长的PAFE。
