Hernandez Steve, Gonzalez Gloria M, McCarthy Dora I, Colombo Arnaldo Lopes, Najvar Laura K, Bocanegera Rosie, Graybill John R
Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
J Antimicrob Chemother. 2004 Aug;54(2):477-80. doi: 10.1093/jac/dkh335. Epub 2004 Jun 23.
Amphotericin B failure is frequently seen in patients with candidaemia caused by Candida rugosa. We evaluated amphotericin B, fluconazole, posaconazole and voriconazole as alternative treatments against infection in mice with two isolates of C. rugosa.
Neutropenic mice were inoculated intravenously with C. rugosa. Amphotericin B, fluconazole, posaconazole and voriconazole were administered for 7 days after infection. Efficacy of the antifungal treatment was assessed by survival and tissue burden of C. rugosa.
All of the four drugs significantly prolonged survival over controls. With both isolates, kidney counts were reduced significantly below controls for amphotericin B, fluconazole and posaconazole. However, voriconazole was less effective than the other antifungals.
Despite poor clinical response to amphotericin B, in vivo data indicate that amphotericin B increases organ clearance and survival over untreated controls. However, although voriconazole improved survival over controls, increased tissue clearance was not seen. This discrepancy may be caused by rapid clearance of voriconazole in mice. These studies suggest fluconazole, posaconazole or voriconazole may be useful alternatives to amphotericin B in therapy of C. rugosa infection.
在由皱落假丝酵母菌引起的念珠菌血症患者中，经常会出现两性霉素B治疗失败的情况。我们评估了两性霉素B、氟康唑、泊沙康唑和伏立康唑作为针对两种皱落假丝酵母菌分离株感染小鼠的替代治疗方法。
对中性粒细胞减少的小鼠静脉接种皱落假丝酵母菌。感染后给予两性霉素B、氟康唑、泊沙康唑和伏立康唑治疗7天。通过皱落假丝酵母菌的存活率和组织负荷来评估抗真菌治疗的效果。
与对照组相比，所有四种药物均显著延长了小鼠的存活时间。对于两种分离株，两性霉素B、氟康唑和泊沙康唑治疗后肾脏中的菌数均显著低于对照组。然而，伏立康唑的效果不如其他抗真菌药物。
尽管两性霉素B的临床反应不佳，但体内数据表明，与未治疗的对照组相比，两性霉素B可提高器官清除率并延长存活时间。然而，虽然伏立康唑提高了小鼠的存活率，但未观察到组织清除率增加。这种差异可能是由于伏立康唑在小鼠体内清除迅速所致。这些研究表明，氟康唑、泊沙康唑或伏立康唑可能是治疗皱落假丝酵母菌感染时两性霉素B的有用替代药物。
