Odds F C, Webster C E, Abbott A B
J Antimicrob Chemother. 1984 Aug;14(2):105-14. doi: 10.1093/jac/14.2.105.
Nine new antifungal agents were tested for their activity in vitro in terms of relative inhibition factors (RIFs) against 26 isolates of Candida species, eight isolates of Aspergillus species and six isolates of dermatophyte fungi. Eight of the new compounds were azole antifungals, the ninth was a phenylmorpholine derivative. Against Candida species, all the novel compounds gave RIFs that were of a similar order to RIFs for established imidazole compounds. Two topical antifungals, butoconazole and terconazole, and two systemic antifungals, itraconazole and vibunazole, gave mean RIFs less than 60% in tests with Candida species, and therefore matched clotrimazole, ketoconazole and tioconazole in terms of RIF. However, none of the new compounds gave RIFs as low as amphotericin B against the Candida isolates. Against Aspergillus isolates, itraconazole, with a mean RIF of 25%, was even more active in vitro than amphotericin B. Vibunazole was as active as ketoconazole against Aspergillus isolates. All the new antifungals except Bay l-9139 gave very low RIFs against dermatophyte isolates, and thus matched established imidazole antifungals for inhibitory effects in vitro. In terms of RIF data, all the nine new compounds tested appear to offer reasonable potential for antifungal chemotherapy in vivo. A similar conclusion would not have been drawn from minimal inhibitory concentration data, which tended to show most of the new antifungals in a very poor light. Tests with amphotericin B, 5-fluorocytosine and ketoconazole showed that RIF can vary substantially with the pH of the test medium. For amphotericin B and ketoconazole the best activity was seen at neutral pH values; for 5-fluorocytosine the greatest inhibitory activity was found at lower pH values.
对9种新型抗真菌药物进行了体外活性测试，测定了它们对26株念珠菌属菌株、8株曲霉菌属菌株和6株皮肤癣菌的相对抑制因子（RIF）。其中8种新化合物为唑类抗真菌药，第9种为苯基吗啉衍生物。对于念珠菌属菌株，所有新型化合物的RIF与已有的咪唑类化合物的RIF处于相似水平。两种局部用抗真菌药布康唑和特康唑，以及两种全身用抗真菌药伊曲康唑和维邦唑，在对念珠菌属菌株的测试中平均RIF低于60%，因此在RIF方面与克霉唑、酮康唑和噻康唑相当。然而，在针对念珠菌分离株的测试中，没有一种新化合物的RIF能低至两性霉素B的水平。对于曲霉菌分离株，伊曲康唑的平均RIF为25%，在体外比两性霉素B更具活性。维邦唑对曲霉菌分离株的活性与酮康唑相当。除Bay l-9139外，所有新型抗真菌药对皮肤癣菌分离株的RIF都非常低，因此在体外抑制作用方面与已有的咪唑类抗真菌药相当。就RIF数据而言，所测试的9种新化合物似乎在体内抗真菌化疗方面都具有合理的潜力。从最低抑菌浓度数据中则得不出类似结论，这些数据往往使大多数新型抗真菌药显得效果很差。对两性霉素B、5-氟胞嘧啶和酮康唑的测试表明，RIF会随测试培养基的pH值有很大变化。对于两性霉素B和酮康唑，在中性pH值时活性最佳；对于5-氟胞嘧啶，在较低pH值时抑制活性最大。
